SELECT - PsA 1: A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Participants With Psoriatic Arthritis Who Have an Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD)
Sponsor
AbbVie (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03104400
Collaborator
(none)
1,705
345
5
87.3
4.9
0.1
Study Details
Study Description
Brief Summary
This study includes two periods. The main objective of Period 1 is to compare the efficacy of upadacitinib 15 mg once daily (QD) and 30 mg QD versus placebo and versus adalimumab (Humira®) in participants with moderately to severely active psoriatic arthritis (PsA) who have had an inadequate response to non-biologic DMARDs (DMARD-IR). Period 1 is also designed to compare the efficacy of upadacitinib 15 mg and 30 mg QD versus placebo for the prevention of structural progression.
The objective of Period 2 is to evaluate the long-term safety, tolerability and efficacy of upadacitinib 15 mg and 30 mg QD in participants who have completed Period 1.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
The study includes a 35-day screening period, a 56-week blinded period (Period 1), a long-term extension period of up to a total treatment duration of approximately 5 years (Period 2), a 30-day follow-up call or visit, and a 70-day follow-up call.
Period 1 includes 24 weeks of randomized, double-blind, placebo-controlled and active comparator-controlled treatment followed by 32 weeks of active comparator-controlled upadacitinib; at Week 24 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment.
Participants who meet eligibility criteria will be randomized in a 2:2:2:1:1 ratio to one of five treatment groups:
-
Group 1: Upadacitinib 15 mg QD
-
Group 2: Upadacitinib 30 mg QD
-
Group 3: Adalimumab 40 mg every other week (EOW)
-
Group 4: Placebo followed by upadacitinib 15 mg QD
-
Group 5: Placebo followed by upadacitinib 30 mg QD
Randomization will be stratified by extent of psoriasis (≥ 3% body surface area [BSA] or < 3% BSA), current use of at least 1 non-biologic DMARD, presence of dactylitis, and presence of enthesitis, except for participants from China and Japan, where randomization for each country will be stratified by extent of psoriasis (≥ 3% BSA or < 3% BSA) only.
Participants who complete the Week 56 visit (end of Period 1) will enter the long-term extension portion of the study, Period 2 (total treatment up to approximately 5 years), and continue study treatment as assigned in Period 1 in a blinded manner until the last subject completes the last visit of Period 1 (Week 56), when study drug assignment in both periods will be unblinded and participants will be dispensed study drug in an open-label fashion until the completion of Period 2.
At Week 16, rescue therapy will be offered to participants classified as non-responders (defined as not achieving at least 20% improvement in tender joint count (TJC) and / or swollen joint count (SJC) at both Week 12 and Week 16). Starting at Week 36, participants who fail to demonstrate at least 20% improvement in either or both TJC and SJC compared to Baseline at 2 consecutive visits will be discontinued from study drug treatment. Additionally, in participants continuing on study drug, starting at the Week 36 visit, initiation of or change in background PsA medication(s) is allowed as per local label.
Study Design
Study Type:
Interventional
Actual Enrollment
:
1705 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Randomized, Double-Blind, Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Active Psoriatic Arthritis Who Have a History of Inadequate Response to at Least One Non-Biologic Disease Modifying Anti-Rheumatic Drug (DMARD) - SELECT - PsA 1
Actual Study Start Date
:
Apr 27, 2017
Actual Primary Completion Date
:
Sep 26, 2019
Anticipated Study Completion Date
:
Aug 4, 2024
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Upadacitinib 15 mg Period 1: Participants receive upadacitinib 15 mg orally once a day (QD) and matching placebo to adalimumab by subcutaneous injection every other week (EOW) for 56 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo to Adalimumab
Administered by subcutaneous injection
|
| Experimental: Upadacitinib 30 mg Period 1: Participants receive upadacitinib 30 mg orally once a day and matching placebo to adalimumab by subcutaneous injection every other week for 56 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo to Adalimumab
Administered by subcutaneous injection
|
| Active Comparator: Adalimumab Period 1: Participants receive adalimumab 40 mg by subcutaneous injection every other week and matching placebo to upadacitinib orally QD for 56 weeks. Period 2: Participants continue to receive adalimumab 40 mg every other week. |
Drug: Adalimumab
Administered by subcutaneous injection
Other Names:
Drug: Placebo to Upadacitinib
Oral tablet
|
| Placebo Comparator: Placebo / Upadacitinib 15 mg Period 1: Participants receive matching placebo to upadacitinib orally once a day for 24 weeks then upadacitinib 15 mg once daily for 32 weeks, and matching placebo to adalimumab by subcutaneous injection EOW for the entire 56 weeks. Period 2: Participants will continue to receive upadacitinib 15 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo to Upadacitinib
Oral tablet
Drug: Placebo to Adalimumab
Administered by subcutaneous injection
|
| Placebo Comparator: Placebo / Upadacitinib 30 mg Period 1: Participants receive matching placebo to upadacitinib orally once a day for 24 weeks then upadacitinib 30 mg once daily for 32 weeks, and matching placebo to adalimumab by subcutaneous injection EOW for the entire 56 weeks. Period 2: Participants will continue to receive upadacitinib 30 mg once daily. |
Drug: Upadacitinib
Oral tablet
Other Names:
Drug: Placebo to Upadacitinib
Oral tablet
Drug: Placebo to Adalimumab
Administered by subcutaneous injection
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [Baseline and Week 12]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
Secondary Outcome Measures
- Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 [Baseline and Week 12]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
- Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16 [Baseline and Week 16]
The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe).
- Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16 [Baseline and Week 16]
PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked). The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score, and was assessed in participants with Baseline psoriasis BSA involvement ≥ 3%.
- Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24 [Baseline and Week 24]
The Sharp-van der Heijde modified scoring method for PsA measures the level of joint damage from radiographs of the hands and feet, and was assessed by 2 independent, blinded readers. Joint erosion severity was assessed in 20 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 320 (worst). Joint space narrowing (JSN) was assessed in 20 joints of each hand and wrist, and 6 joints of each foot, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 208 (worst). Joints with gross osteolysis or pencil in cup were assigned the maximum score for both erosions and JSN. The total mTSS score is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 528 (worst). A negative change from Baseline indicates improvement in joint damage.
- Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 [Week 24]
A participant was classified as achieving MDA if 5 of the following 7 criteria were met: Tender joint count (out of 68 joints) ≤ 1 Swollen joint count (out of 66 joints) ≤ 1 PASI score ≤ 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤ 3% Patient's assessment of pain ≤ 1.5 (NRS from 0 to 10) Patient's Global Assessment of disease activity ≤ 2 (NRS from 0 to 10) HAQ-DI score ≤ 0.5 (index score ranges from 0 to 3) Leeds Enthesitis Index ≤ 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6)
- Percentage of Participants With Resolution of Enthesitis at Week 24 [Week 24]
Resolution of enthesitis is defined as a Leeds Enthesitis Index (LEI) score = 0. LEI is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions. Tenderness on examination is recorded as either present (coded as 1), absent (coded as 0), or not assessed for each of the 6 sites. The LEI is calculated by taking the sum of the scores from the 6 sites. The LEI ranges from 0 to 6 (worst).
- Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab [Baseline and Week 12]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
- Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 [Baseline and Week 12]
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement.
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 [Baseline and Week 12]
The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement.
- Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab [Baseline and Week 12]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With Resolution of Dactylitis at Week 24 [Week 24]
Resolution of dactylitis is defined as a Leeds Dactylitis Index (LDI) score = 0. The Leeds Dactylitis Index (LDI) is a score based on finger circumference and tenderness, assessed and summed across all dactylitic digits (fingers and toes). The presence of a dactylitic digit is defined as at least one affected AND tender digit with circumference increase over reference digit ≥ 10%. The reference digit circumference is either the contralateral digit (unaffected digit on opposite hand or foot) if available, or from a standard reference table if otherwise. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and reference digit is multiplied by the tenderness score for each affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis.
- Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab [Baseline and Week 12]
Participants were asked to indicate the severity of their arthritis pain within the previous week on a numerical rating scale (NRS) from 0 to 10. A score of 0 indicates "no pain" and a score of 10 indicates "worst possible pain." A negative change from Baseline indicates improvement.
- Change From Baseline in HAQ-DI - Superiority Versus Adalimumab [Baseline and Week 12]
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
- Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16 [Baseline and Week 16]
The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement.
- Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [Baseline and Week 12]
Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: ≥ 50% improvement in 68-tender joint count; ≥ 50% improvement in 66-swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [Baseline and Week 12]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: ≥ 70% improvement in 68-tender joint count; ≥ 70% improvement in 66-swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
- Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2 [Baseline and Week 2]
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Clinical diagnosis of PsA with symptom onset at least 6 months prior to the Screening Visit and fulfillment of the Classification Criteria for PsA (CASPAR) criteria.
-
Participant has active disease at Baseline defined as >= 3 tender joints (based on 68 joint counts) and >= 3 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.
-
Presence of either at Screening:
-
= 1 erosion on x-ray as determined by central imaging review or;
-
high-sensitivity C-reactive protein (hs-CRP) > laboratory defined upper limit of normal (ULN).
-
Diagnosis of active plaque psoriasis or documented history of plaque psoriasis.
-
Participant has had an inadequate response (lack of efficacy after a minimum 12 week duration of therapy) to previous or current treatment with at least 1 non-biologic DMARD at maximally tolerated dose (methotrexate (MTX), sulfasalazine (SSZ), leflunomide (LEF), cyclosporine, apremilast, bucillamin or iguratimod), or participant has an intolerance to or contraindication for DMARDs as defined by the investigator.
-
Participant who is on current treatment with concomitant non-biologic DMARDs at study entry must be on <= 2 non-biologic DMARDs (except the combination of MTX and leflunomide). The following non-biologic DMARDs are allowed: MTX, sulfasalazine, leflunomide, apremilast, hydroxychloroquine (HCQ) , bucillamine or iguratimod, and have been ongoing for >= 12 weeks and at stable dose for >= 4 weeks prior to the Baseline Visit. No other DMARDs are permitted during the study.
- Participants who need to discontinue DMARDs prior to the Baseline Visit to comply with this inclusion criterion must follow the procedure specified below or at least five times the mean terminal elimination half-life of a drug:
-
= 8 weeks for LEF if no elimination procedure was followed, or adhere to an elimination procedure (i.e., 11 days with cholestyramine, or 30 days washout with activated charcoal or as per local label);
-
= 4 weeks for all others.
Exclusion Criteria:
-
Prior exposure to any Janus Kinase (JAK) inhibitor (including but not limited to ruxolitinib, tofacitinib, baricitinib, and filgotinib).
-
Current treatment with > 2 non-biologic DMARDs; or use of DMARDs other than methotrexate, sulfasalazine, leflunomide, apremilast, hydroxychloroquine, bucillamine, or iguratimod; or use of methotrexate in combination with leflunomide.
-
History of fibromyalgia, any arthritis with onset prior to age 17 years, or current diagnosis of inflammatory joint disease other than PsA (including, but not limited to rheumatoid arthritis, gout, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, systemic lupus erythematosus). Prior history of reactive arthritis or axial spondyloarthritis including ankylosing spondylitis and nonradiographic axial spondyloarthritis is permitted if documentation of change in diagnosis to PsA or additional diagnosis of PsA is made. Prior history of fibromyalgia is permitted if documentation of change in diagnosis to PsA or documentation that the diagnosis of fibromyalgia was made incorrectly.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rheum Assoc of North Alabama /ID# 163231 | Huntsville | Alabama | United States | 35801 |
| 2 | SunValley Arthritis Center, Lt /ID# 161221 | Peoria | Arizona | United States | 85381 |
| 3 | AZ Arthritis and Rheumotology Research, PLLC /ID# 159981 | Phoenix | Arizona | United States | 85032-9306 |
| 4 | AZ Arthritis and Rheumotology Research, PLLC /ID# 160033 | Phoenix | Arizona | United States | 85032-9306 |
| 5 | AZ Arthritis and Rheumotology Research, PLLC /ID# 160036 | Phoenix | Arizona | United States | 85032-9306 |
| 6 | AZ Arthritis & Rheuma Research /ID# 160037 | Phoenix | Arizona | United States | 85032 |
| 7 | AZ Arth & Rheum Res /ID# 166381 | Tucson | Arizona | United States | 85704 |
| 8 | Little Rock Diagnostics Clinic /ID# 165161 | Little Rock | Arkansas | United States | 72205 |
| 9 | Covina Arthritis Clinic /ID# 159891 | Covina | California | United States | 91722 |
| 10 | St. Joseph Heritage Healthcare /ID# 159980 | Fullerton | California | United States | 92835 |
| 11 | C.V. Mehta MD, Med Corporation /ID# 161216 | Hemet | California | United States | 92543 |
| 12 | Care Access Research, Huntingt /ID# 160038 | Huntington Beach | California | United States | 92648 |
| 13 | Kotha and Kotha /ID# 159823 | La Mesa | California | United States | 91942 |
| 14 | TriWest Research Associates- La Mesa /ID# 159887 | La Mesa | California | United States | 91942 |
| 15 | Arthritis & Osteo Medical Ctr /ID# 166760 | La Palma | California | United States | 90623-1728 |
| 16 | University of California, Los Angeles /ID# 164542 | Los Angeles | California | United States | 90095 |
| 17 | VA Sacramento Medical Center /ID# 164196 | Mather | California | United States | 95655 |
| 18 | East Bay Rheumatology Medical /ID# 166382 | San Leandro | California | United States | 94578 |
| 19 | Inland Rheum Clin Trials Inc. /ID# 159828 | Upland | California | United States | 91786 |
| 20 | Medvin Clinical Research /ID# 160034 | Whittier | California | United States | 90606 |
| 21 | Denver Arthritis Clinic /ID# 159873 | Denver | Colorado | United States | 80230 |
| 22 | Arthritis and Rheum Clin N. CO /ID# 160039 | Fort Collins | Colorado | United States | 80528 |
| 23 | Colorado Arthritis Associates /ID# 159847 | Lakewood | Colorado | United States | 80228 |
| 24 | Stamford Therapeutics Consorti /ID# 165131 | Stamford | Connecticut | United States | 06905 |
| 25 | Clinical Res of West FL, Inc. /ID# 159829 | Clearwater | Florida | United States | 33765 |
| 26 | International Medical Research - Daytona /ID# 160040 | Daytona Beach | Florida | United States | 32117 |
| 27 | Omega Research Maitland, LLC /ID# 164193 | DeBary | Florida | United States | 32713-2260 |
| 28 | Precision Research Org, LLC /ID# 161287 | Miami Lakes | Florida | United States | 33016-1501 |
| 29 | LeJenue Research Associates /ID# 170965 | Miami | Florida | United States | 33126 |
| 30 | Medallion Clinical Research Institute, LLC /ID# 161228 | Naples | Florida | United States | 34102 |
| 31 | Millennium Research /ID# 159822 | Ormond Beach | Florida | United States | 32174 |
| 32 | Arthritis Center, Inc. /ID# 163465 | Palm Harbor | Florida | United States | 34684 |
| 33 | Gulf Region Clinical Res Inst /ID# 159851 | Pensacola | Florida | United States | 32514 |
| 34 | BayCare Medical Group /ID# 159792 | Saint Petersburg | Florida | United States | 33705 |
| 35 | W. Broward Rheum Assoc Inc. /ID# 161388 | Tamarac | Florida | United States | 33321 |
| 36 | Clinical Research of West Florida, Inc /ID# 160063 | Tampa | Florida | United States | 33606-1246 |
| 37 | University of South Florida /ID# 161286 | Tampa | Florida | United States | 33612 |
| 38 | BayCare Medical Group, Inc. /ID# 159879 | Tampa | Florida | United States | 33614-7101 |
| 39 | Florida Medical Clinic /ID# 159992 | Zephyrhills | Florida | United States | 33542 |
| 40 | Institute of Arthritis Researc /ID# 165873 | Idaho Falls | Idaho | United States | 83404 |
| 41 | Advanced Clinical Research /ID# 159894 | Meridian | Idaho | United States | 83642 |
| 42 | Great Lakes Clinical Trials /ID# 163435 | Chicago | Illinois | United States | 60640 |
| 43 | OrthoIllinois /ID# 164546 | Rockford | Illinois | United States | 61114-4937 |
| 44 | Clinical Investigation Specialists - Skokie /ID# 160062 | Skokie | Illinois | United States | 60076 |
| 45 | Deerbrook Medical Associates /ID# 159804 | Vernon Hills | Illinois | United States | 60061 |
| 46 | Graves Gilbert Clinic /ID# 161285 | Bowling Green | Kentucky | United States | 42101 |
| 47 | Four Rivers Clinical Research /ID# 159982 | Paducah | Kentucky | United States | 42001 |
| 48 | Ochsner Clinic Foundation-New Orleans /ID# 165672 | New Orleans | Louisiana | United States | 70121 |
| 49 | Johns Hopkins University /ID# 167665 | Baltimore | Maryland | United States | 21224 |
| 50 | Klein & Associates, M.D., P.A. /ID# 164013 | Cumberland | Maryland | United States | 21502 |
| 51 | The Center for Rheumatology & Bone Research /ID# 159874 | Wheaton | Maryland | United States | 20902 |
| 52 | Tufts Medical Center /ID# 165144 | Boston | Massachusetts | United States | 02111 |
| 53 | Mansfield Health Center /ID# 159805 | Mansfield | Massachusetts | United States | 02048 |
| 54 | Clinical Pharmacology Study Gr /ID# 158700 | Worcester | Massachusetts | United States | 01605 |
| 55 | Univ of Michigan Hospitals /ID# 164014 | Ann Arbor | Michigan | United States | 48109 |
| 56 | Aa Mrc Llc /Id# 159846 | Grand Blanc | Michigan | United States | 48439 |
| 57 | Advanced Rheumatology, PC /ID# 159893 | Lansing | Michigan | United States | 48910 |
| 58 | Beals Institute PC /ID# 163128 | Lansing | Michigan | United States | 48917 |
| 59 | Shores Rheumatology, PC /ID# 159889 | Saint Clair Shores | Michigan | United States | 48081 |
| 60 | St. Luke's Hospital of Duluth /ID# 165671 | Duluth | Minnesota | United States | 55805 |
| 61 | Clayton Medical Associates dba Saint Louis Rheumatology /ID# 159878 | Saint Louis | Missouri | United States | 63119-3845 |
| 62 | Clinvest Research LLC /ID# 161227 | Springfield | Missouri | United States | 65810-2607 |
| 63 | Glacier View Research Institut /ID# 167023 | Kalispell | Montana | United States | 59901 |
| 64 | Westroads Clinical Research /ID# 159979 | Omaha | Nebraska | United States | 68114 |
| 65 | Dartmouth-Hitchcock Medical Center /ID# 161235 | Lebanon | New Hampshire | United States | 03756 |
| 66 | Arthritis and Osteoporosis Associates /ID# 159802 | Freehold | New Jersey | United States | 07728 |
| 67 | Atlantic Coast Research /ID# 159799 | Toms River | New Jersey | United States | 08755 |
| 68 | Ocean Rheumatology, PA /ID# 163898 | Toms River | New Jersey | United States | 08755 |
| 69 | Arthritis and Osteo Assoc /ID# 159994 | Las Cruces | New Mexico | United States | 88011 |
| 70 | Santa Fe Rheumatology /ID# 163783 | Santa Fe | New Mexico | United States | 87505 |
| 71 | NYU Langone Rheum Assoc /ID# 159985 | Lake Success | New York | United States | 11554 |
| 72 | NYU Langone Medical Center /ID# 163230 | New York | New York | United States | 10016-6402 |
| 73 | St. Lawrence Health System /ID# 159848 | Potsdam | New York | United States | 13676 |
| 74 | American Health Research /ID# 164354 | Charlotte | North Carolina | United States | 28207 |
| 75 | DJL Clinical Research, PLLC /ID# 161390 | Charlotte | North Carolina | United States | 28210-8508 |
| 76 | M3-Emerging Medical Research, LLC /ID# 161391 | Durham | North Carolina | United States | 27704 |
| 77 | Physicians East, PA /ID# 159872 | Greenville | North Carolina | United States | 27834 |
| 78 | Cape Fear Arthritis Care /ID# 161224 | Leland | North Carolina | United States | 28451 |
| 79 | Shanahan Rheuma & Immuno /ID# 159987 | Raleigh | North Carolina | United States | 27617 |
| 80 | Trinity Health Med Arts Clinic /ID# 159800 | Minot | North Dakota | United States | 58701 |
| 81 | MetroHealth Medical Center /ID# 159888 | Cleveland | Ohio | United States | 44109 |
| 82 | The Ohio State University /ID# 159892 | Columbus | Ohio | United States | 43210 |
| 83 | Clinical Research Source, Inc. /ID# 164545 | Perrysburg | Ohio | United States | 43551 |
| 84 | STAT Research, Inc. /ID# 161392 | Vandalia | Ohio | United States | 45377-9464 |
| 85 | Health Research of Oklahoma /ID# 159880 | Oklahoma City | Oklahoma | United States | 73103-2400 |
| 86 | Altoona Ctr Clinical Res /ID# 159852 | Duncansville | Pennsylvania | United States | 16635 |
| 87 | PA Regional Center /ID# 165670 | Wyomissing | Pennsylvania | United States | 19610 |
| 88 | Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 163464 | Summerville | South Carolina | United States | 29486-7887 |
| 89 | West Tennessee Research Inst /ID# 159871 | Jackson | Tennessee | United States | 38305 |
| 90 | Rheumatology Consultants, PLLC /ID# 159796 | Knoxville | Tennessee | United States | 37909 |
| 91 | Dr. Ramesh Gupta /ID# 160061 | Memphis | Tennessee | United States | 38119 |
| 92 | Accurate Clinical Management /ID# 159905 | Baytown | Texas | United States | 77521 |
| 93 | Diagnostic Group Integrated He /ID# 159794 | Beaumont | Texas | United States | 77701 |
| 94 | Arth and Osteo Clin Brazo Valley /ID# 163436 | College Station | Texas | United States | 77845 |
| 95 | PCCR Solution /ID# 205723 | Colleyville | Texas | United States | 76034 |
| 96 | Adriana Pop-Moody MD Clinic PA /ID# 159984 | Corpus Christi | Texas | United States | 78404 |
| 97 | Metroplex Clinical Research /ID# 159785 | Dallas | Texas | United States | 75231 |
| 98 | Rheumatic Disease Clin Res Ctr /ID# 161240 | Houston | Texas | United States | 77004 |
| 99 | Rheumatology Clinic of Houston /ID# 161234 | Houston | Texas | United States | 77065 |
| 100 | "DMCR-Texas Cent for Drug Dev /ID# 164191 | Houston | Texas | United States | 77081 |
| 101 | West Texas Clinical Research /ID# 205722 | Lubbock | Texas | United States | 79410-1198 |
| 102 | P&I Clinical Research /ID# 159826 | Lufkin | Texas | United States | 75904-3132 |
| 103 | SW Rheumatology Res. LLC /ID# 159993 | Mesquite | Texas | United States | 75150 |
| 104 | Trinity Universal Research Association /ID# 205721 | Plano | Texas | United States | 75024-5283 |
| 105 | Arthritis & Osteo Ctr of S. TX /ID# 163784 | San Antonio | Texas | United States | 78232 |
| 106 | Arthritis Clinic of Central TX /ID# 164049 | San Marcos | Texas | United States | 78666 |
| 107 | DM Clinical Research /ID# 161735 | Tomball | Texas | United States | 77375 |
| 108 | Arthritis & Osteoporosis Clinic /ID# 159786 | Waco | Texas | United States | 76710 |
| 109 | Arthritis Clinic of N. VA, P.C /ID# 159849 | Arlington | Virginia | United States | 22205 |
| 110 | Ctr for Arth and Rheum Disease /ID# 159830 | Chesapeake | Virginia | United States | 23320 |
| 111 | Swedish Medical Center /ID# 159890 | Seattle | Washington | United States | 98104 |
| 112 | Arthritis Northwest, PLLC /ID# 166380 | Spokane | Washington | United States | 99204 |
| 113 | West Virginia Research Inst /ID# 159791 | South Charleston | West Virginia | United States | 25309 |
| 114 | Aurora Rheumatology and Immunotherapy Center /ID# 160043 | Franklin | Wisconsin | United States | 53132 |
| 115 | Centro Medico Privado/Reuma /ID# 159775 | San Miguel de Tucuman | Ciuadad Autonoma De Buenos Aires | Argentina | 4000 |
| 116 | Centro Integral de Medicina Respiratoria (CIMER) /ID# 211237 | San Miguel de Tucuman | Tucuman | Argentina | 4000 |
| 117 | Organizacion Medica de Investigacion (OMI) /ID# 160118 | Buenos Aires | Argentina | 1015 | |
| 118 | Hospital General de Agudos Ram /ID# 164378 | Buenos Aires | Argentina | 1221 | |
| 119 | Psoriahue Med Interdisciplinar /ID# 160506 | Buenos Aires | Argentina | 1425 | |
| 120 | Inst. de Rehab. Psicofisica /ID# 165154 | Caba | Argentina | 1428 | |
| 121 | Instituto CAICI /ID# 160119 | Rosario, Santa FE | Argentina | 2000 | |
| 122 | Centro Integral de Medicina Re /ID# 160258 | SAN Miguel DE Tucuman, Latam | Argentina | 4000 | |
| 123 | Centro de Enfermedades del Hígado y Aparato Digestivo /ID# 165795 | Santa Fe | Argentina | 2000 | |
| 124 | Emeritus Research Sydney /ID# 166780 | Botany | New South Wales | Australia | 2019 |
| 125 | The Queen Elizabeth Hospital /ID# 169333 | Woodville | South Australia | Australia | 5011 |
| 126 | Barwon Rheumatology /ID# 166782 | Geelong | Victoria | Australia | 3220 |
| 127 | Heidelberg Repatriation Hospital /ID# 167450 | Heidelberg West | Victoria | Australia | 3081 |
| 128 | Brest Regional Hospital /ID# 164535 | Brest | Belarus | 224027 | |
| 129 | Healthcare Institution /ID# 164536 | Grodno | Belarus | 230017 | |
| 130 | First City Clinical Hospital /ID# 164534 | Minsk | Belarus | 220013 | |
| 131 | Reuma clinic /ID# 164243 | Genk | Belgium | 3600 | |
| 132 | University Clinical Centre of the Republic of Srpska /ID# 164503 | Banja Luka | Republika Srpska | Bosnia and Herzegovina | 78000 |
| 133 | University Clinical Hospital Mostar /ID# 165799 | Mostar | Bosnia and Herzegovina | 88000 | |
| 134 | Clinical Center University of Sarajevo /ID# 164502 | Sarajevo | Bosnia and Herzegovina | 71000 | |
| 135 | Instituto de Ciencias Farmacêuticas /ID# 163274 | Aparecida de Goiania | Goias | Brazil | 74935-530 |
| 136 | CIP - Centro Internacional de Pesquisa /ID# 161821 | Goiânia | Goias | Brazil | 74110-120 |
| 137 | CMiP - Centro Mineiro de Pesquisa Ltda - ME /ID# 161819 | Juiz de Fora | Minas Gerais | Brazil | 36010-570 |
| 138 | EDUMED Educacao em Saude S/S L /ID# 161816 | Curitiba | Parana | Brazil | 80440-080 |
| 139 | Instituto de Educação e Pesquisa do Hospital Moinhos de Vento /ID# 161813 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-001 |
| 140 | Hospital de Clinicas de Porto Alegre /ID# 161820 | Porto Alegre | Rio Grande Do Sul | Brazil | 90035-903 |
| 141 | LMK Sevicos Medicos S/S /ID# 161812 | Porto Alegre | Rio Grande Do Sul | Brazil | 90480-000 |
| 142 | Hospital das Clinicas da Faculdade de Medicina de Ribeirão Preto - USP /ID# 163273 | Ribeirao Preto | Sao Paulo | Brazil | 14049-900 |
| 143 | Faculdade de Medicina do ABC /ID# 163491 | Santo André | Sao Paulo | Brazil | 09060-870 |
| 144 | CEMEC - Centro Multidisciplinar de Estudos Clínicos do ABC /ID# 161810 | Santo André | Sao Paulo | Brazil | 09190-510 |
| 145 | CPCLIN - Centro de Pesquisas Clínicas /ID# 161818 | Sao Paulo | Brazil | 01244-030 | |
| 146 | Department of Rheumatology, Mu /ID# 169606 | Plovdiv | Bulgaria | 4003 | |
| 147 | Excelsior Medical Center /ID# 169609 | Sofia | Bulgaria | 1407 | |
| 148 | Multiprofile Hospital for Active Treatment - Sofia at Military Medical Academy /ID# 169608 | Sofia | Bulgaria | 1606 | |
| 149 | UMHAT Sv. Ivan Rilski /ID# 202393 | Sofia | Bulgaria | 1612 | |
| 150 | Medical Centre Synexus Sofia /ID# 202394 | Sofia | Bulgaria | 1784 | |
| 151 | Medical Centre Synexus Sofia, branch Stara Zagora /ID# 202524 | Stara Zagora | Bulgaria | 6000 | |
| 152 | Diagnostic Consultative Center /ID# 169607 | Varna | Bulgaria | 9000 | |
| 153 | Percuro Clinical Research, Ltd /ID# 157823 | Victoria | British Columbia | Canada | V8V 3M9 |
| 154 | Manitoba Clinic /ID# 157829 | Winnipeg | Manitoba | Canada | R3A 1M3 |
| 155 | Ciads /Id# 157831 | Winnipeg | Manitoba | Canada | R3N 0K6 |
| 156 | The Waterside Clinic /ID# 157826 | Barrie | Ontario | Canada | L4M 6L2 |
| 157 | Groupe de Recherche en Maladies Osseuses Inc /ID# 157824 | Sainte-foy | Quebec | Canada | G1V 3M7 |
| 158 | Ctr. de Recherche Musculo-Sque /ID# 207069 | Trois-rivières | Quebec | Canada | G8Z 1Y2 |
| 159 | M y F Estudios Clínicos Ltda. /ID# 168722 | Ñuñoa | Region Metropolitana De Santiago | Chile | 7750495 |
| 160 | CTR Estudios SpA /ID# 206217 | Providencia | Chile | 7500571 | |
| 161 | Centro Inter Estud Clin CIEC /ID# 168725 | Santiago | Chile | 8420383 | |
| 162 | Prosalud Ltda. /ID# 169546 | Santiago | Chile | ZC:7510047 | |
| 163 | Clinica Dermacross S.A /ID# 168726 | Vitacura Santiago | Chile | 7640881 | |
| 164 | 1st Aff Hosp of Bengbu Medical College /ID# 201021 | Bengbu | Anhui | China | 233004 |
| 165 | Peking University Third Hospital /ID# 201973 | Beijing | Beijing | China | 100191 |
| 166 | The First Affiliated Hospital of Shantou University Medical College /ID# 203371 | Shantou | Guangdong | China | 515041 |
| 167 | Zhuzhou Central Hospital /ID# 200201 | Zhuzhou | Hunan | China | 412007 |
| 168 | The First Affiliated Hospital of Baotou Medical College, Inner Monggolia Univers /ID# 171204 | Baotou | Inner Mongolia | China | 014016 |
| 169 | The First People's Hospital of Linyi /ID# 201970 | Linyi | Shandong | China | 276034 |
| 170 | Huashan Hospital of Fudan University /ID# 202191 | Shanghai | Shanghai | China | 200040 |
| 171 | Shanghai Changhai Hospital /ID# 200202 | Shanghai | Shanghai | China | 200433 |
| 172 | West China Hospital /ID# 200199 | Chengdu | Sichuan | China | 610041 |
| 173 | Ningbo First Hospital /ID# 201874 | Ningbo | Zhejiang | China | 315010 |
| 174 | The Aff Hosp Inner Mongolia /ID# 207787 | Huhehaote | China | 010050 | |
| 175 | First Affiliated Hospital of Kunming Medical University /ID# 201264 | Kunming | China | 650032 | |
| 176 | Affiliated hospital of nantong university /ID# 208234 | Nantong | China | 226001 | |
| 177 | The First Affiliated Hospital of Soochow University /ID# 201875 | Soochow | China | 215006 | |
| 178 | People's Hospital of Xinjiang /ID# 201592 | Urumqi | China | 830001 | |
| 179 | Centro de Investigacion en Reumatologia CIREEM /ID# 166030 | Bogota | Cundinamarca | Colombia | 110231 |
| 180 | Fundacion Centro de Investigac /Id# 168201 | Antioquia | Colombia | 050022 | |
| 181 | Ctr Int de Reum del Caribe SAS /ID# 164051 | Barranquilla | Colombia | 80002 | |
| 182 | Preventive Care Sas /Id# 163781 | Chia | Colombia | 250001 | |
| 183 | Hospital Pablo Tobon Uribe /ID# 164233 | Medellín | Colombia | ||
| 184 | Poliklinika Repromed /ID# 203555 | Zagreb | Grad Zagreb | Croatia | 10000 |
| 185 | Klinicki bolnicki centar Rijeka /ID# 161159 | Rijeka | Primorsko-goranska Zupanija | Croatia | 51000 |
| 186 | Medical Center Kuna-Peric /ID# 161160 | Zagreb | Croatia | 10000 | |
| 187 | Poliklinika Bonifarm /ID# 206662 | Zagreb | Croatia | 10000 | |
| 188 | Revmatologicka ambulance /ID# 159637 | Prague 4 | Praha 4 | Czechia | 140 00 |
| 189 | Revmatologicka ambulance /ID# 159671 | Prague 4 | Praha 4 | Czechia | 140 00 |
| 190 | Revmatologie Bruntal, s.r.o /ID# 159636 | Bruntál | Czechia | 79201 | |
| 191 | Artroscan s.r.o. /ID# 159634 | Ostrava | Czechia | 722 00 | |
| 192 | Medical Plus, s.r.o. /ID# 159635 | Uherské Hradište | Czechia | 686 01 | |
| 193 | Center of Clinical and Basic Research /ID# 163870 | Tallinn | Harjumaa | Estonia | 10128 |
| 194 | MediTrials /ID# 163706 | Tartu | Tartumaa | Estonia | 50406 |
| 195 | East Tallinn Central Hospital /ID# 163790 | Tallinn | Estonia | 10138 | |
| 196 | Rheumazentrum Ruhrgebiet /ID# 163930 | Herne | Nordrhein-Westfalen | Germany | 44649 |
| 197 | Immanuel-Krankenhaus /ID# 163931 | Berlin-buch | Germany | 13125 | |
| 198 | University Clinic Carl Gustav /ID# 163926 | Dresden | Germany | 01307 | |
| 199 | Polikilinik fuer Rheumatologie /ID# 163933 | Duesseldorf | Germany | 40225 | |
| 200 | Cent fur Innovative Diagnostik /ID# 163927 | Frankfurt | Germany | 60590 | |
| 201 | Hamburger Rheuma Forschungszentrum II im MVZ Rheumatologie und Autoimmunmedizin /ID# 204421 | Hamburg | Germany | 20095 | |
| 202 | Dr. med. Jochen Walter FA fuer /ID# 168638 | Rendsburg | Germany | 24768 | |
| 203 | Med. Universitaetsklinik Inner /ID# 163929 | Tuebingen | Germany | 72076 | |
| 204 | General Hospital of Athens Laiko /ID# 163476 | Athens | Attiki | Greece | 115 27 |
| 205 | General Hospital of Athens Laiko /ID# 163478 | Athens | Attiki | Greece | 115 27 |
| 206 | University General Hospital Attikon /ID# 163477 | Athens | Attiki | Greece | 12462 |
| 207 | Naval Hospital of Athens /ID# 163486 | Athens | Greece | 11521 | |
| 208 | University General Hospital of Heraklion PA.G.N.I /ID# 163472 | Heraklion | Greece | 71110 | |
| 209 | Reg Gen Univ Hosp Larissa /ID# 163496 | Larisa | Greece | 41110 | |
| 210 | Prince of Wales Hospital /ID# 163506 | Hong Kong | Hong Kong | 999077 | |
| 211 | Queen Mary Hospital /ID# 162492 | Hong Kong | Hong Kong | 999077 | |
| 212 | Tuen Mun Hospital /ID# 162493 | Tuen Mun | Hong Kong | 999077 | |
| 213 | Synexus Magyarorszag Kft. - Gyula DRS /ID# 202209 | Gyula | Bekes | Hungary | 5700 |
| 214 | Qualiclinic Kft. /ID# 163278 | Budapest III | Pest | Hungary | 1036 |
| 215 | Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatok.- Klinikai Kutatasi O. /ID# 202584 | Nyíregyháza | Szabolcs-Szatmar-Bereg | Hungary | 4400 |
| 216 | Synexus Magyarorszag Kft. - Zalaegerszeg AS /ID# 201884 | Zalaegerszeg | Zala | Hungary | 8900 |
| 217 | Betegapolo Irgalmas Rend - Budai Irgalmasrendi Korhaz /ID# 170719 | Budapest | Hungary | 1023 | |
| 218 | Revita Reumatologiai Rendelo /ID# 163277 | Budapest | Hungary | 1027 | |
| 219 | Obudai Egeszsegugyi Centrum Kft. /ID# 163279 | Budapest | Hungary | 1036 | |
| 220 | Synexus Magyarorszag Kft. /ID# 203012 | Budapest | Hungary | 1036 | |
| 221 | Debreceni Egyetem Kenezy Gyula /ID# 163276 | Debrecen | Hungary | 4031 | |
| 222 | Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 163275 | Veszprem | Hungary | 8200 | |
| 223 | St Vincent's University Hosp /ID# 161073 | Dublin | Ireland | D04 T6F4 | |
| 224 | Croom Orthopaedic Hospital /ID# 164998 | Limerick | Ireland | V35 F434 | |
| 225 | Tel Aviv Sourasky Medical Center /ID# 169845 | Tel Aviv-Yafo | Tel-Aviv | Israel | 6423906 |
| 226 | The Lady Davis Carmel MC /ID# 170262 | Haifa | Israel | 3436212 | |
| 227 | Sheba Medical Center /ID# 202532 | Ramat Gan | Israel | 5239424 | |
| 228 | AOU Federico II /ID# 202411 | Naples | Campania | Italy | 80131 |
| 229 | Azienda Unita Sanitaria Locale/IRCCS c/o Arcispedale Santa Maria Nuova /ID# 161090 | Reggio Emilia | Emilia-Romagna | Italy | 42123 |
| 230 | Policlinico Universitario Campus Bio-Medico /ID# 162306 | Rome | Lazio | Italy | 00128 |
| 231 | Ospedali Riuniti Universita /ID# 161085 | Ancona | Italy | 60023 | |
| 232 | Azienda Ospedaliera Universitaria Policlinico "G. Rodolico - San Marco" /Id# 161084 | Catania | Italy | 95123 | |
| 233 | Nagoya City University Hospital /ID# 162564 | Nagoya-shi | Aichi | Japan | 467-8602 |
| 234 | Fukuoka University Hospital /ID# 162086 | Fukuoka-shi | Fukuoka | Japan | 814-0180 |
| 235 | Hospital of the University of Occupational and Environmental Health /ID# 161473 | Kitakyushu-shi | Fukuoka | Japan | 807-8556 |
| 236 | Mie University Hospital /ID# 162080 | Tsu-shi | Mie | Japan | 514-8507 |
| 237 | National Hospital Organization Osaka Minami Medical Center /ID# 162590 | Kawachinagano-shi | Osaka | Japan | 586-8521 |
| 238 | St.Luke's International Hospital /ID# 162016 | Chuo-ku | Tokyo | Japan | 104-8560 |
| 239 | Ajou University Hospital /ID# 163891 | Suwon-si | Gyeonggido | Korea, Republic of | 16499 |
| 240 | Inha University Hospital /ID# 163890 | Jung-gu | Incheon Gwang Yeogsi | Korea, Republic of | 22332 |
| 241 | M &M Centrs /Id# 161483 | Adazi | Latvia | LV2167 | |
| 242 | D.Saulites-Kandevicas PP in Cardiology and Rheumatology /ID# 161488 | Liepaja | Latvia | 3401 | |
| 243 | Clinic ORTO /ID# 161486 | Riga | Latvia | 1005 | |
| 244 | P. Stradins Clinical Univ Hosp /ID# 164442 | Riga | Latvia | LV-1002 | |
| 245 | VAKK dr. Kildos Clinic /ID# 167257 | Kaunas | Lithuania | 50128 | |
| 246 | Klaipeda University Hospital /ID# 167258 | Klaipeda | Lithuania | 92288 | |
| 247 | Public Institution Republican /ID# 165155 | Siauliai | Lithuania | 76231 | |
| 248 | Vilnius University Hospital /ID# 165123 | Vilnius | Lithuania | LT-08661 | |
| 249 | Hospital Raja Permaisuri Bainun /ID# 161099 | Ipoh | Perak | Malaysia | 30450 |
| 250 | Hospital Tuanku Ja afar /ID# 161096 | Seremban | Malaysia | 70300 | |
| 251 | CINTRE, Centro de Investigación y Tratamiento Reumatológico SC /ID# 164006 | Mexico City | Ciudad De Mexico | Mexico | 11850 |
| 252 | Instituto Jalisciense de Metabolismo SC /ID# 164005 | Guadalajara | Jalisco | Mexico | 44670 |
| 253 | Invest y Biomed de Chihuahua /ID# 164007 | Chihuahua | Mexico | 31000 | |
| 254 | Medisch Centrum Leeuwarden /ID# 161575 | Leeuwarden | Netherlands | 8934 AD | |
| 255 | Erasmus Medisch Centrum /ID# 161092 | Rotterdam | Netherlands | 3015 CE | |
| 256 | Maasstad Ziekenhuis /ID# 160168 | Rotterdam | Netherlands | 3079 DZ | |
| 257 | Waikato Hospital /ID# 166415 | Hamilton | Waikato | New Zealand | 3204 |
| 258 | North Shore Hospital /ID# 169409 | Auckland | New Zealand | 0622 | |
| 259 | Middlemore Hospital /ID# 166414 | Auckland | New Zealand | 2025 | |
| 260 | Porter Rheumatology Ltd /ID# 200421 | Nelson | New Zealand | 7010 | |
| 261 | Timaru Rheumatology Studies /ID# 166413 | Timaru | New Zealand | 7910 | |
| 262 | Helse Forde /ID# 167853 | Forde | Sogn Og Fjordane | Norway | 6812 |
| 263 | St. Olavs Hospital HF /ID# 163321 | Trondheim | Sor-Trondelag | Norway | 7006 |
| 264 | Synexus Polska Sp. z o.o. /ID# 204506 | Wrocław | Dolnoslaskie | Poland | 50-381 |
| 265 | NZOZ Nasz Lekarz /ID# 163774 | Toruń | Kujawsko-pomorskie | Poland | 87-100 |
| 266 | Salve Medica Sp. z o.o. S.K. /ID# 206300 | Lodz | Lodzkie | Poland | 91-211 |
| 267 | Malopolskie Centrum Kliniczne /ID# 163777 | Cracow | Malopolskie | Poland | 30-149 |
| 268 | Synexus Polska Sp. z o.o. Oddzial w Gdansku /ID# 206299 | Gdańsk | Pomorskie | Poland | 80-382 |
| 269 | Synexus Polska Sp. z o.o. Oddzial w Gdyni /ID# 207157 | Gdynia | Pomorskie | Poland | 81-537 |
| 270 | Synexus Polska Sp. z o.o. Oddzial Katowice /ID# 204510 | Katowice | Slaskie | Poland | 40-040 |
| 271 | ETYKA-Osrodek Badan Klinicznyc /ID# 163776 | Olsztyn | Warminsko-mazurskie | Poland | 10-117 |
| 272 | Centrum Kliniczno-Badawcze /ID# 161830 | Elblag | Poland | 82-300 | |
| 273 | Krakowskie Centrum Medyczne /ID# 206302 | Krakow | Poland | 31-501 | |
| 274 | Synexus Polska Sp. z o.o. Oddzial w Poznaniu /ID# 207158 | Poznan | Poland | 60-702 | |
| 275 | Medycyna Kliniczna /ID# 166288 | Warsaw | Poland | 00-874 | |
| 276 | Synexus Polska Sp. z.o.o. /ID# 203987 | Warsaw | Poland | 01-192 | |
| 277 | Reumatika - Centrum Reumatologii NZOZ /ID# 161831 | Warsaw | Poland | 02-691 | |
| 278 | Instituto Portugues De Reumatologia /ID# 165858 | Lisbon | Lisboa | Portugal | 1050-034 |
| 279 | Centro Hospitalar Lisboa Ocidental, EPE /ID# 165861 | Lisbon | Lisboa | Portugal | 1349-019 |
| 280 | Centro Hospitalar de Vila Nova Gaia/Espinho, EPE /ID# 165862 | Vila Nova De Gaia | Porto | Portugal | 4434-502 |
| 281 | Centro Hospitalar Lisboa Norte, EPE /ID# 165860 | Lisboa | Portugal | 1649-035 | |
| 282 | Hospital CUF Descobertas /ID# 165866 | Lisbon | Portugal | 1998-018 | |
| 283 | Hospital Beatriz Angelo /ID# 165865 | Loures | Portugal | 2674-514 | |
| 284 | Unidade Local De Saude Do Alto Minho /ID# 165863 | Viana Do Castelo | Portugal | 4901-858 | |
| 285 | Cruz-Santana, Carolina, PR /ID# 163307 | Carolina | Puerto Rico | 00985 | |
| 286 | Ponce Medical School Foundation /ID# 163920 | Ponce | Puerto Rico | 00716-0377 | |
| 287 | GCM Medical Group, PSC /ID# 162160 | San Juan | Puerto Rico | 00917 | |
| 288 | Family Outpatient clinic#4 LLC /ID# 164530 | Korolev | Moskva | Russian Federation | 141060 |
| 289 | LLC Medical Center /ID# 164529 | Novosibirsk | Novosibirskaya Oblast | Russian Federation | 630099 |
| 290 | Kazan State Medical University /ID# 164531 | Kazan | Tatarstan, Respublika | Russian Federation | 420012 |
| 291 | Moscow S.P.Botkin City Clinica /ID# 164533 | Moscow | Russian Federation | 125284 | |
| 292 | State budgetary institution /ID# 164532 | St. Petersburg | Russian Federation | 192242 | |
| 293 | Institute for Rheumatology /ID# 166217 | Belgrade | Beograd | Serbia | 11000 |
| 294 | Institute for Rheumatology /ID# 166223 | Belgrade | Beograd | Serbia | 11000 |
| 295 | Institute for Rheumatology /ID# 166229 | Belgrade | Beograd | Serbia | 11000 |
| 296 | Institute for Rheumatology /ID# 166231 | Belgrade | Beograd | Serbia | 11000 |
| 297 | Military Medical Academy /ID# 166293 | Belgrade | Beograd | Serbia | 11000 |
| 298 | Singapore General Hospital /ID# 161094 | Singapore | Central Singapore | Singapore | 169068 |
| 299 | Tan Tock Seng Hospital /ID# 161095 | Singapore | Singapore | 308433 | |
| 300 | MEDMAN s.r.o. /ID# 165892 | Martin | Slovakia | 036 01 | |
| 301 | Reumatologická ambulancia Reum.hapi s.r.o. /ID# 166486 | Nové Mesto Nad Váhom | Slovakia | 915 01 | |
| 302 | Slovak research center Team Member, Thermium s.r.o. /ID# 166489 | Pieštany | Slovakia | 921 01 | |
| 303 | Univ Medical Ctr Ljubljana /ID# 164212 | Ljubljana | Slovenia | 1000 | |
| 304 | University Medical Ctr Maribor /ID# 169260 | Maribor | Slovenia | 2000 | |
| 305 | General Hospital Murska Sobota /ID# 164211 | Murska Sobota | Slovenia | 9000 | |
| 306 | Greenacres Hospital /ID# 164190 | Port Elizabeth | Eastern Cape | South Africa | 6045 |
| 307 | Wits Clinical Research Site /ID# 163919 | Johannesburg | Gauteng | South Africa | 2193 |
| 308 | University of Pretoria /ID# 163852 | Pretoria | Gauteng | South Africa | 0001 |
| 309 | Jakaranda Hospital /ID# 164242 | Pretoria | Gauteng | South Africa | 0002 |
| 310 | Arthritis Clinical Research Tr /ID# 163855 | Cape Town | Western Cape | South Africa | 7405 |
| 311 | Winelands Medical Research Ctr /ID# 163853 | Stellenbosch | Western Cape | South Africa | 7600 |
| 312 | Hospital Universitario A Coruña - CHUAC /ID# 161129 | A Coruña | A Coruna | Spain | 15006 |
| 313 | Hospital Campus de la Salud /ID# 170760 | Granada | Spain | 18016 | |
| 314 | Hospital Universitario Ramon y Cajal /ID# 161130 | Madrid | Spain | 28034 | |
| 315 | Hospital Universitario 12 de Octubre /ID# 163198 | Madrid | Spain | 28041 | |
| 316 | Kantonsspital St. Gallen /ID# 158131 | St. Gallen | Sankt Gallen | Switzerland | 9007 |
| 317 | HFR Fribourg - Hopital Canton /ID# 162090 | Fribourg | Switzerland | 1708 | |
| 318 | China Medical University Hosp /ID# 159402 | Taichung City | Taichung | Taiwan | 40447 |
| 319 | Chung Shan Medical University /ID# 159403 | Taichung | Taiwan | 404 | |
| 320 | National Taiwan University Hospital /ID# 160878 | Taipei City | Taiwan | 10002 | |
| 321 | Taipei Veterans General Hosp /ID# 166222 | Taipei City | Taiwan | 11217 | |
| 322 | Linkou Chang Gung Memorial Ho /ID# 166221 | Taoyuan City | Taiwan | 33305 | |
| 323 | Cukurova Universitesi Tip Fakultesi /ID# 162516 | Saricam Adana | Adana | Turkey | 01330 |
| 324 | Hacettepe Universitesi Tip Fak /ID# 162518 | Sihhiye | Ankara | Turkey | 06100 |
| 325 | Bakirkoy Dr. Sadi Konuk Training & Research Hospital /ID# 162517 | Istanbul | Turkey | 34147 | |
| 326 | Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi /ID# 163383 | Istanbul | Turkey | 34899 | |
| 327 | Necmettin Erbakan Universitesi /ID# 163382 | Meram Konya | Turkey | 42080 | |
| 328 | Sakarya Universitesi Egitim /ID# 163397 | Sakarya | Turkey | 54100 | |
| 329 | State Institution L. T. Malaya Therapy National Institution of NAMS of Ukraine /ID# 164170 | Kharkiv | Kharkivska Oblast | Ukraine | 61039 |
| 330 | Lviv Regional Clinical Hospita /ID# 164178 | Lviv | Lvivska Oblast | Ukraine | 79013 |
| 331 | Kharkiv Regional Council Regional Clinical Hospital /ID# 210189 | Kharkiv | Ukraine | 61058 | |
| 332 | NSC Strazhesko Ist Cardiology /ID# 164043 | Kiev | Ukraine | 03680 | |
| 333 | Med Ctr of Private High Ed Ins /ID# 208527 | Kyiv | Ukraine | 02002 | |
| 334 | Medical Center of LLC Medbud-Clinic /ID# 208528 | Kyiv | Ukraine | 03037 | |
| 335 | Kyiv Railway Clinical Hosp No.2 /ID# 208951 | Kyiv | Ukraine | 03049 | |
| 336 | LLC Revmocentr /ID# 164177 | Kyiv | Ukraine | 04070 | |
| 337 | MNI KRC Kyiv Regional Clinical Hospital /ID# 210188 | Kyiv | Ukraine | 04107 | |
| 338 | Odessa National Medical Univ /ID# 164244 | Odesa | Ukraine | 65026 | |
| 339 | Vinnytsia Regional Clinical Hospital n.a. M.I.Pyrogov /ID# 164245 | Vinnytsia | Ukraine | 21018 | |
| 340 | Whipps Cross Univ Hospital /ID# 161055 | London | London, City Of | United Kingdom | E11 1NR |
| 341 | Guy's and St Thomas' NHS Found /ID# 161065 | London | London, City Of | United Kingdom | SE1 9RT |
| 342 | Christchurch Hospital /ID# 162702 | Christchurch | United Kingdom | BH23 2JX | |
| 343 | UH Coventry & Warwickshire /ID# 162701 | Coventry | United Kingdom | CV2 2DX | |
| 344 | Glasgow Royal Infirmary /ID# 162703 | Glasgow | United Kingdom | G4 0SF | |
| 345 | Luton & Dunstable University Hospital /ID# 162704 | Luton | United Kingdom | LU4 0DZ |
Sponsors and Collaborators
- AbbVie
Investigators
- Study Director: AbbVie Inc., AbbVie
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03104400
Other Study ID Numbers:
- M15-572
- 2016-004130-24
First Posted:
Apr 7, 2017
Last Update Posted:
Jan 25, 2022
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Keywords provided by AbbVie
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study is being conducted at 281 sites in 44 countries and was initiated in April 2017. Adults with active psoriatic arthritis (PsA) and a history of inadequate response or intolerance to at least one non-biologic disease modifying anti-rheumatic drug (DMARD) were eligible for enrollment. The study is ongoing; results up to Week 56 are reported. |
|---|---|
| Pre-assignment Detail | Participants were randomized in a 1:1:2:2:2 ratio to one of five treatment groups. Randomization was stratified by extent of psoriasis (≥ 3% body surface area [BSA] or < 3% BSA), current use of at least 1 non-biologic DMARD, presence of dactylitis, and presence of enthesitis, except for participants from China and Japan, where randomization was stratified by extent of psoriasis (≥ 3% BSA or < 3% BSA) only. |
| Arm/Group Title | Placebo / Upadacitinib 15 mg | Placebo / Upadacitinib 30 mg | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants randomized to receive matching placebo to upadacitinib orally once a day (QD) for 24 weeks followed by upadacitinib 15 mg once daily for 32 weeks (Weeks 24 to 56), as well as matching placebo to adalimumab administered by subcutaneous injection every other week (EOW) from Weeks 1 to 56. | Participants randomized to receive matching placebo to upadacitinib orally QD for 24 weeks followed by upadacitinib 30 mg once daily for 32 weeks (Weeks 24 to 56), in addition to matching placebo to adalimumab administered by subcutaneous injection EOW from Weeks 1 to 56. | Participants randomized to receive adalimumab 40 mg by subcutaneous injection EOW and matching placebo to upadacitinib orally QD for 56 weeks. | Participants randomized to receive upadacitinib 15 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks. | Participants randomized to receive upadacitinib 30 mg orally QD and matching placebo to adalimumab by subcutaneous injection EOW for 56 weeks. |
| Period Title: Overall Study | |||||
| STARTED | 211 | 212 | 429 | 430 | 423 |
| Received Study Drug | 211 | 212 | 429 | 429 | 423 |
| Completed Week 24 | 190 | 193 | 404 | 408 | 394 |
| COMPLETED | 177 | 178 | 370 | 379 | 366 |
| NOT COMPLETED | 34 | 34 | 59 | 51 | 57 |
Baseline Characteristics
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab by subcutaneous (SC) injection EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. | Total of all reporting groups |
| Overall Participants | 423 | 429 | 429 | 423 | 1704 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
50.4
(12.21)
|
51.4
(12.04)
|
51.6
(12.19)
|
49.9
(12.41)
|
50.8
(12.22)
|
| Age, Customized (Count of Participants) | |||||
| < 65 years |
367
86.8%
|
362
84.4%
|
367
85.5%
|
371
87.7%
|
1467
86.1%
|
| 65 - < 75 years |
52
12.3%
|
61
14.2%
|
52
12.1%
|
46
10.9%
|
211
12.4%
|
| ≥ 75 years |
4
0.9%
|
6
1.4%
|
10
2.3%
|
6
1.4%
|
26
1.5%
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
211
49.9%
|
222
51.7%
|
238
55.5%
|
236
55.8%
|
907
53.2%
|
| Male |
212
50.1%
|
207
48.3%
|
191
44.5%
|
187
44.2%
|
797
46.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||
| Hispanic or Latino |
66
15.6%
|
65
15.2%
|
59
13.8%
|
53
12.5%
|
243
14.3%
|
| Not Hispanic or Latino |
357
84.4%
|
364
84.8%
|
370
86.2%
|
370
87.5%
|
1461
85.7%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||
| White |
377
89.1%
|
375
87.4%
|
386
90%
|
377
89.1%
|
1515
88.9%
|
| Black or African American |
3
0.7%
|
2
0.5%
|
1
0.2%
|
3
0.7%
|
9
0.5%
|
| American Indian/Alaska Native |
2
0.5%
|
2
0.5%
|
0
0%
|
2
0.5%
|
6
0.4%
|
| Native Hawaiian or other Pacific Islander |
1
0.2%
|
2
0.5%
|
0
0%
|
1
0.2%
|
4
0.2%
|
| Asian |
37
8.7%
|
41
9.6%
|
37
8.6%
|
34
8%
|
149
8.7%
|
| Multiple |
3
0.7%
|
7
1.6%
|
5
1.2%
|
6
1.4%
|
21
1.2%
|
| Extent of Psoriasis (Count of Participants) | |||||
| < 3% BSA |
212
50.1%
|
218
50.8%
|
215
50.1%
|
213
50.4%
|
858
50.4%
|
| ≥ 3% BSA |
211
49.9%
|
211
49.2%
|
214
49.9%
|
210
49.6%
|
846
49.6%
|
| Current Use of at Least 1 Non-Biologic DMARD (Count of Participants) | |||||
| Yes |
347
82%
|
347
80.9%
|
353
82.3%
|
346
81.8%
|
1393
81.7%
|
| No |
76
18%
|
82
19.1%
|
76
17.7%
|
77
18.2%
|
311
18.3%
|
| Presence of Dactylitis (Count of Participants) | |||||
| Yes |
126
29.8%
|
127
29.6%
|
136
31.7%
|
127
30%
|
516
30.3%
|
| No |
297
70.2%
|
302
70.4%
|
293
68.3%
|
296
70%
|
1188
69.7%
|
| Presence of Enthesitis (Count of Participants) | |||||
| Yes |
322
76.1%
|
330
76.9%
|
333
77.6%
|
331
78.3%
|
1316
77.2%
|
| No |
101
23.9%
|
99
23.1%
|
96
22.4%
|
92
21.7%
|
388
22.8%
|
| Duration of Psoriatic Arthritis Symptoms (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
9.3
(8.58)
|
9.1
(8.78)
|
9.2
(8.63)
|
9.3
(8.28)
|
9.2
(8.56)
|
| Duration of PsA Diagnosis (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
6.2
(7.01)
|
5.9
(7.06)
|
6.2
(7.41)
|
5.9
(6.37)
|
6.1
(6.97)
|
| Tender Joint Count (TJC) (joints) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [joints] |
20.0
(14.34)
|
20.1
(13.82)
|
20.4
(14.72)
|
19.4
(13.32)
|
20.0
(14.05)
|
| Swollen Joint Count (SJC) (joints) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [joints] |
11.0
(8.16)
|
11.6
(8.75)
|
11.6
(9.31)
|
10.6
(7.06)
|
11.2
(8.37)
|
| Patient's Assessment of Pain (units on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [units on a scale] |
6.1
(2.14)
|
6.0
(2.08)
|
6.2
(2.07)
|
5.9
(2.05)
|
6.0
(2.09)
|
| Patient's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [units on a scale] |
6.3
(2.04)
|
6.3
(2.03)
|
6.6
(2.03)
|
6.4
(2.07)
|
6.4
(2.04)
|
| Physician's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [units on a scale] |
6.5
(1.64)
|
6.6
(1.65)
|
6.7
(1.62)
|
6.5
(1.68)
|
6.5
(1.65)
|
| Health Assessment Questionnaire - Disability Index (HAQ-DI) (units on a scale) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [units on a scale] |
1.12
(0.639)
|
1.12
(0.626)
|
1.15
(0.653)
|
1.09
(0.630)
|
1.12
(0.637)
|
| High-sensitivity C-reactive Protein (hsCRP) (mg/L) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [mg/L] |
11.48
(15.800)
|
10.91
(15.463)
|
11.00
(14.910)
|
11.49
(15.355)
|
11.22
(15.373)
|
Outcome Measures
| Title | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
36.2
8.6%
|
65.0
15.2%
|
70.6
16.5%
|
78.5
18.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 34.5 | |
| Confidence Interval |
(2-Sided) 95% 28.2 to 40.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 42.3 | |
| Confidence Interval |
(2-Sided) 95% 36.3 to 48.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 |
|---|---|
| Description | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 392 | 406 | 404 | 398 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-0.14
|
-0.34
|
-0.42
|
-0.47
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | Least Squares (LS) Mean Difference |
| Estimated Value | -0.28 | |
| Confidence Interval |
(2-Sided) 95% -0.35 to -0.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.34 | |
| Confidence Interval |
(2-Sided) 95% -0.40 to -0.27 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants Achieving a Static Investigator Global Assessment (sIGA) of Psoriasis of 0 or 1 and at Least a 2-point Improvement From Baseline (sIGA 0/1) at Week 16 |
|---|---|
| Description | The sIGA is a 5 point scale ranging from 0 to 4, based on the investigator's assessment of the average elevation, erythema, and scaling of all psoriatic lesions at the current visit. A lower score indicates less severe psoriasis (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate and 4 = severe). |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with a Baseline sIGA score ≥ 2; participants who prematurely discontinued from study drug prior to Week 16 or for whom sIGA data were missing at Week 16 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 313 | 330 | 322 | 324 |
| Number (95% Confidence Interval) [percentage of participants] |
10.9
2.6%
|
38.5
9%
|
41.9
9.8%
|
54.0
12.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 31.1 | |
| Confidence Interval |
(2-Sided) 95% 24.7 to 37.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 43.1 | |
| Confidence Interval |
(2-Sided) 95% 36.7 to 49.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants Achieving Psoriasis Area Severity Index (PASI) 75 Response at Week 16 |
|---|---|
| Description | PASI is a composite score based on the percentage of the body surface area (BSA) affected by psoriasis and the intensity of erythema (reddening), induration (thickening or hardening of the skin), and desquamation (peeling of the skin) of lesions assessed at 4 anatomic sites (head, upper extremities, trunk, and lower extremities). At each location, the percentage of BSA involvement is assigned a score from 0 (no involvement) to 6 (90% to 100% involvement), and erythema, induration, and desquamation are scored on a scale from 0 (no symptoms) to 4 (very marked). The PASI score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI-75 response is the percentage of participants who achieved at least a 75% reduction (improvement) from Baseline in PASI score, and was assessed in participants with Baseline psoriasis BSA involvement ≥ 3%. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with Baseline psoriasis BSA involvement ≥ 3%; participants who prematurely discontinued from study drug prior to Week 16 or for whom PASI data were missing at Week 16 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 211 | 211 | 214 | 210 |
| Number (95% Confidence Interval) [percentage of participants] |
21.3
5%
|
53.1
12.4%
|
62.6
14.6%
|
62.4
14.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 41.3 | |
| Confidence Interval |
(2-Sided) 95% 32.8 to 49.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 41.1 | |
| Confidence Interval |
(2-Sided) 95% 32.5 to 49.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Change From Baseline in Modified PsA Total Sharp/Van Der Heijde Score (mTSS) at Week 24 |
|---|---|
| Description | The Sharp-van der Heijde modified scoring method for PsA measures the level of joint damage from radiographs of the hands and feet, and was assessed by 2 independent, blinded readers. Joint erosion severity was assessed in 20 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 320 (worst). Joint space narrowing (JSN) was assessed in 20 joints of each hand and wrist, and 6 joints of each foot, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 208 (worst). Joints with gross osteolysis or pencil in cup were assigned the maximum score for both erosions and JSN. The total mTSS score is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 528 (worst). A negative change from Baseline indicates improvement in joint damage. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data at Baseline; linear extrapolation was used for participants who discontinued prior to Week 24 or who were rescued prior to Week 24. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 372 | 384 | 391 | 383 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
0.25
|
0.01
|
-0.04
|
0.03
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model including treatment and the stratification factor current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.29 | |
| Confidence Interval |
(2-Sided) 95% -0.44 to -0.14 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.0069 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ANCOVA model including treatment and the stratification factor current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.21 | |
| Confidence Interval |
(2-Sided) 95% -0.36 to -0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants Achieving Minimal Disease Activity (MDA) at Week 24 |
|---|---|
| Description | A participant was classified as achieving MDA if 5 of the following 7 criteria were met: Tender joint count (out of 68 joints) ≤ 1 Swollen joint count (out of 66 joints) ≤ 1 PASI score ≤ 1 (score ranges from 0 - 72) or percent BSA involved with psoriasis ≤ 3% Patient's assessment of pain ≤ 1.5 (NRS from 0 to 10) Patient's Global Assessment of disease activity ≤ 2 (NRS from 0 to 10) HAQ-DI score ≤ 0.5 (index score ranges from 0 to 3) Leeds Enthesitis Index ≤ 1 (assesses the presence or absence of enthesitis at 3 bilateral sites, with an overall score range from 0 to 6) |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 24 or for whom data were missing at Week 24, or who met the rescue criteria at Week 16 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
12.3
2.9%
|
33.3
7.8%
|
36.6
8.5%
|
45.4
10.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 24.3 | |
| Confidence Interval |
(2-Sided) 95% 18.8 to 29.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 33.1 | |
| Confidence Interval |
(2-Sided) 95% 27.4 to 38.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With Resolution of Enthesitis at Week 24 |
|---|---|
| Description | Resolution of enthesitis is defined as a Leeds Enthesitis Index (LEI) score = 0. LEI is an enthesitis measure developed specifically for PsA and assesses the presence or absence of tenderness at the following 3 bilateral enthesial sites: medial femoral condyles, lateral epicondyles of the humerus, and Achilles tendon insertions. Tenderness on examination is recorded as either present (coded as 1), absent (coded as 0), or not assessed for each of the 6 sites. The LEI is calculated by taking the sum of the scores from the 6 sites. The LEI ranges from 0 to 6 (worst). |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with a Baseline LEI > 0; participants who prematurely discontinued from study drug prior to Week 24 or for whom data were missing at Week 24, or who met the rescue criteria at Week 16 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 241 | 265 | 270 | 267 |
| Number (95% Confidence Interval) [percentage of participants] |
32.4
7.7%
|
47.2
11%
|
53.7
12.5%
|
57.7
13.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 21.3 | |
| Confidence Interval |
(2-Sided) 95% 13.0 to 29.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 25.3 | |
| Confidence Interval |
(2-Sided) 95% 16.9 to 33.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With an ACR20 Response at Week 12 - Non-inferiority Versus Adalimumab |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
36.2
8.6%
|
65.0
15.2%
|
70.6
16.5%
|
78.5
18.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority of each upadacitinib dose versus adalimumab was assessed using Koch's 3-arm approach; non-inferiority was achieved if upadacitinib preserved at least 50% of the placebo-subtracted adalimumab effect. The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Koch 3-Arm Test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent Adalimumab Effect Preservation |
| Estimated Value | 119.381 | |
| Confidence Interval |
(2-Sided) 95% 97.987 to 147.942 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The percent of adalimumab effect preservation is the point estimate of 3-arm non-inferiority analysis, which is calculated by (Upadacitinib - Placebo) / (Adalimumab - Placebo) * 100. | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Non-Inferiority | |
| Comments | Non-inferiority of each upadacitinib dose versus adalimumab was assessed using Koch's 3-arm approach; non-inferiority was achieved if upadacitinib preserved at least 50% of the placebo-subtracted adalimumab effect. The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Koch 3-Arm Test | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Percent Adalimumab Effect Preservation |
| Estimated Value | 146.604 | |
| Confidence Interval |
(2-Sided) 95% 122.817 to 180.398 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The percent of adalimumab effect preservation is the point estimate of 3-arm non-inferiority analysis, which is calculated by (Upadacitinib - Placebo) / (Adalimumab - Placebo) * 100. | |
| Title | Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 |
|---|---|
| Description | The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from Baseline score indicates an improvement. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 394 | 410 | 405 | 398 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
3.19
|
6.82
|
7.86
|
8.90
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 4.67 | |
| Confidence Interval |
(2-Sided) 95% 3.67 to 5.67 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 5.72 | |
| Confidence Interval |
(2-Sided) 95% 4.71 to 6.72 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
| Title | Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 |
|---|---|
| Description | The FACIT-Fatigue questionnaire is a self-administered patient questionnaire that consists of 13 questions designed to measure the degree of fatigue experienced by participants in the previous 7 days, including physical fatigue (e.g., I feel tired), functional fatigue (e.g., trouble finishing things), emotional fatigue (e.g., frustration), and social consequences of fatigue (e.g., limits social activity). Participants respond to the questions on a scale from 0 'not at all' to 4 'very much'. The FACIT Fatigue score is computed by summing the item scores, after reversing those items that are worded in the negative direction. The FACIT-Fatigue subscale score ranges from 0 to 52, where higher scores represent less fatigue. A positive change from Baseline indicates improvement. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 394 | 410 | 404 | 398 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
2.8
|
5.7
|
6.3
|
7.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 3.5 | |
| Confidence Interval |
(2-Sided) 95% 2.4 to 4.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 4.3 | |
| Confidence Interval |
(2-Sided) 95% 3.1 to 5.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With an ACR20 Response at Week 12 - Superiority Versus Adalimumab |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
36.2
8.6%
|
65.0
15.2%
|
70.6
16.5%
|
78.5
18.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.0815 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 5.6 | |
| Confidence Interval |
(2-Sided) 95% -0.6 to 11.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Adalimumab | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 13.5 | |
| Confidence Interval |
(2-Sided) 95% 7.5 to 19.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Adalimumab | |
| Title | Percentage of Participants With Resolution of Dactylitis at Week 24 |
|---|---|
| Description | Resolution of dactylitis is defined as a Leeds Dactylitis Index (LDI) score = 0. The Leeds Dactylitis Index (LDI) is a score based on finger circumference and tenderness, assessed and summed across all dactylitic digits (fingers and toes). The presence of a dactylitic digit is defined as at least one affected AND tender digit with circumference increase over reference digit ≥ 10%. The reference digit circumference is either the contralateral digit (unaffected digit on opposite hand or foot) if available, or from a standard reference table if otherwise. Tenderness of affected digits is assessed on a scale from 0 [none] to 3 [worst]. The ratio of circumference between an affected digit and reference digit is multiplied by the tenderness score for each affected digit. The results from each involved digit are summed to provide the final LDI. A higher LDI indicates worse dactylitis. |
| Time Frame | Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with a Baseline LDI > 0; participants who prematurely discontinued from study drug prior to Week 24 or for whom data were missing at Week 24, or who met the rescue criteria at Week 16 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 126 | 127 | 136 | 127 |
| Number (95% Confidence Interval) [percentage of participants] |
39.7
9.4%
|
74.0
17.2%
|
76.5
17.8%
|
79.5
18.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 36.8 | |
| Confidence Interval |
(2-Sided) 95% 25.7 to 47.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 39.8 | |
| Confidence Interval |
(2-Sided) 95% 28.8 to 50.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Change From Baseline in Patient's Assessment of Pain - Superiority Versus Adalimumab |
|---|---|
| Description | Participants were asked to indicate the severity of their arthritis pain within the previous week on a numerical rating scale (NRS) from 0 to 10. A score of 0 indicates "no pain" and a score of 10 indicates "worst possible pain." A negative change from Baseline indicates improvement. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 392 | 406 | 404 | 398 |
| Least Squares Mean (95% Confidence Interval) [units on a scale] |
-0.9
|
-2.3
|
-2.3
|
-2.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.8970 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | 0.0 | |
| Confidence Interval |
(2-Sided) 95% -0.3 to 0.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Adalimumab | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.0028 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.5 | |
| Confidence Interval |
(2-Sided) 95% -0.7 to -0.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Adalimumab | |
| Title | Change From Baseline in HAQ-DI - Superiority Versus Adalimumab |
|---|---|
| Description | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 12 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 392 | 406 | 404 | 398 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
-0.14
|
-0.34
|
-0.42
|
-0.47
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | 0.0162 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.08 | |
| Confidence Interval |
(2-Sided) 95% -0.15 to -0.01 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Adalimumab | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Adalimumab 40 mg, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -0.14 | |
| Confidence Interval |
(2-Sided) 95% -0.20 to -0.07 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Adalimumab | |
| Title | Change From Baseline in Self-Assessment of Psoriasis Symptoms (SAPS) Questionnaire at Week 16 |
|---|---|
| Description | The SAPS is an 11-item self-assessment of psoriasis symptoms that includes questions on: pain, itching, redness, scaling, flaking, bleeding, burning, stinging, tenderness, pain due to skin cracking, and joint pain. Each item is scored from 0 to 10, with 0 being least severe and 10 being most severe. The total score is generated by summing the 11 items and ranges from 0 to 110 (worst). A negative change from Baseline in the total score indicates improvement. |
| Time Frame | Baseline and Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with longitudinal data from observed cases up to Week 16 was used. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 388 | 407 | 396 | 395 |
| Least Squares Mean (95% Confidence Interval) [score on a scale] |
-8.2
|
-22.7
|
-25.3
|
-28.1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -17.1 | |
| Confidence Interval |
(2-Sided) 95% -19.6 to -14.6 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | The overall type I error rate of the primary and the 14 ranked secondary endpoints was controlled using a two-part sequential graphical multiple testing procedure starting with the primary endpoint using α/2 for each dose followed by a prespecified α transfer path. | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not tested for statistical significance because the hierarchical testing procedures stopped at ACR 20 at Week 12 superiority test of upadacitinib 15 mg versus adalimumab 40 mg. | |
| Method | Mixed Effect Model Repeated Measurement | |
| Comments | MMRM analysis including treatment, visit, treatment-by-visit interaction, current DMARD use (yes/no) as fixed factors and Baseline value as covariate. | |
| Method of Estimation | Estimation Parameter | LS Mean Difference |
| Estimated Value | -19.8 | |
| Confidence Interval |
(2-Sided) 95% -22.3 to -17.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Treatment Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from Baseline were classified as meeting the ACR50 response criteria: ≥ 50% improvement in 68-tender joint count; ≥ 50% improvement in 66-swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
13.2
3.1%
|
37.5
8.7%
|
37.5
8.7%
|
51.8
12.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel (CMH) test adjusted for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 24.3 | |
| Confidence Interval |
(2-Sided) 95% 18.7 to 29.9 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 38.5 | |
| Confidence Interval |
(2-Sided) 95% 32.8 to 44.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: ≥ 70% improvement in 68-tender joint count; ≥ 70% improvement in 66-swollen joint count; and ≥ 70% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
2.4
0.6%
|
13.8
3.2%
|
15.6
3.6%
|
25.3
6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 13.3 | |
| Confidence Interval |
(2-Sided) 95% 9.5 to 17.0 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 22.9 | |
| Confidence Interval |
(2-Sided) 95% 18.5 to 27.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
| Title | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 2 |
|---|---|
| Description | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: ≥ 20% improvement in 68-tender joint count; ≥ 20% improvement in 66-swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High-sensitivity C-reactive protein (hsCRP). |
| Time Frame | Baseline and Week 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set; participants who prematurely discontinued from study drug prior to Week 2 or for whom ACR data were missing at Week 2 were considered non-responders. |
| Arm/Group Title | Placebo | Adalimumab 40 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW. |
| Measure Participants | 423 | 429 | 429 | 423 |
| Number (95% Confidence Interval) [percentage of participants] |
12.1
2.9%
|
30.3
7.1%
|
28.2
6.6%
|
38.3
9.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 15 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 16.1 | |
| Confidence Interval |
(2-Sided) 95% 10.9 to 21.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Upadacitinib 30 mg |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | This comparison was not part of the pre-specified multiplicity testing sequence. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Cochran-Mantel-Haenszel test adjusting for the main stratification factor of current DMARD use (yes/no). | |
| Method of Estimation | Estimation Parameter | Response Rate Difference |
| Estimated Value | 26.2 | |
| Confidence Interval |
(2-Sided) 95% 20.7 to 31.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Response Rate Difference = Upadacitinib - Placebo | |
Adverse Events
| Time Frame | Adverse events are reported for weeks 1 to 24 and weeks 1 to 56 for participants who received upadacitinib or adalimumab. | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||
| Arm/Group Title | Placebo: Week 1-24 | Upadacitinib 15 mg: Week 1-24 | Upadacitinib 30 mg: Week 1-24 | Adalimumab: Week 1-24 | Upadacitinib 15 mg: Week 1-56 | Upadacitinib 30 mg: Week 1-56 | Adalimumab: Week 1-56 | |||||||
| Arm/Group Description | Participants received matching placebo to upadacitinib orally QD and matching placebo to adalimumab SC EOW for 24 weeks. | Participants received upadacitinib 15 mg orally QD and matching placebo to adalimumab SC EOW for 24 weeks. | Participants received upadacitinib 30 mg orally QD and matching placebo to adalimumab SC EOW for 24 weeks. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD for 24 weeks. | Participants originally randomized to upadacitinib 15 mg received upadacitinib 15 mg for 56 weeks and participants originally randomized to placebo who switched to upadacitinib 15 mg at Week 24 and received upadacitinib 15 mg for 32 weeks. All participants also received matching placebo to adalimumab SC EOW. | Participants originally randomized to upadacitinib 30 mg received upadacitinib 30 mg for 56 weeks and participants originally randomized to placebo who switched to upadacitinib 30 mg at Week 24 and received upadacitinib 30 mg for 32 weeks. All participants also received matching placebo to adalimumab SC EOW. | Participants received adalimumab 40 mg SC EOW and matching placebo to upadacitinib orally QD for 56 weeks. | |||||||
All Cause Mortality |
||||||||||||||
| Placebo: Week 1-24 | Upadacitinib 15 mg: Week 1-24 | Upadacitinib 30 mg: Week 1-24 | Adalimumab: Week 1-24 | Upadacitinib 15 mg: Week 1-56 | Upadacitinib 30 mg: Week 1-56 | Adalimumab: Week 1-56 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/423 (0.2%) | 0/429 (0%) | 0/423 (0%) | 0/429 (0%) | 2/617 (0.3%) | 1/613 (0.2%) | 0/429 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| Placebo: Week 1-24 | Upadacitinib 15 mg: Week 1-24 | Upadacitinib 30 mg: Week 1-24 | Adalimumab: Week 1-24 | Upadacitinib 15 mg: Week 1-56 | Upadacitinib 30 mg: Week 1-56 | Adalimumab: Week 1-56 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/423 (3.1%) | 15/429 (3.5%) | 27/423 (6.4%) | 17/429 (4%) | 40/617 (6.5%) | 58/613 (9.5%) | 35/429 (8.2%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| IRON DEFICIENCY ANAEMIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| LYMPHOID TISSUE HYPERPLASIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| NORMOCHROMIC NORMOCYTIC ANAEMIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Cardiac disorders | ||||||||||||||
| ACUTE MYOCARDIAL INFARCTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| ATRIAL FIBRILLATION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| CARDIAC ARREST | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| CARDIAC FAILURE CONGESTIVE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| CORONARY ARTERY DISEASE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| MYOCARDIAL INFARCTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 2/613 (0.3%) | 2 | 0/429 (0%) | 0 |
| Eye disorders | ||||||||||||||
| CATARACT | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| DIPLOPIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| EYELID PTOSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| ANAL FISTULA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| COLITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| DUODENAL ULCER | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| DUODENAL ULCER HAEMORRHAGE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| DYSPEPSIA | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| ENTERITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| FAECALOMA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| GASTRIC ULCER PERFORATION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| GASTRITIS EROSIVE | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| GASTRODUODENAL HAEMORRHAGE | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| GASTROINTESTINAL HAEMORRHAGE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| GASTROOESOPHAGEAL REFLUX DISEASE | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| HAEMORRHOIDS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| HIATUS HERNIA | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| INTESTINAL POLYP | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| LARGE INTESTINE POLYP | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| VOMITING | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| General disorders | ||||||||||||||
| CHEST PAIN | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PAIN | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| PYREXIA | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 2/613 (0.3%) | 2 | 1/429 (0.2%) | 1 |
| Hepatobiliary disorders | ||||||||||||||
| CHOLELITHIASIS | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PORTAL VEIN THROMBOSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Infections and infestations | ||||||||||||||
| ABSCESS LIMB | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| ANAL ABSCESS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| APPENDICITIS | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 3/613 (0.5%) | 3 | 0/429 (0%) | 0 |
| ARTHRITIS BACTERIAL | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| ATYPICAL PNEUMONIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 2/423 (0.5%) | 2 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 2/613 (0.3%) | 2 | 0/429 (0%) | 0 |
| BACTERAEMIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| BONE ABSCESS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| BREAST CELLULITIS | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| BRONCHITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 2/613 (0.3%) | 2 | 0/429 (0%) | 0 |
| CELLULITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| DIVERTICULITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| ERYSIPELAS | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| H1N1 INFLUENZA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| HERPES ZOSTER | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| HERPES ZOSTER CUTANEOUS DISSEMINATED | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| INFLUENZA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| LARYNGITIS | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| LUNG INFECTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PNEUMOCYSTIS JIROVECII PNEUMONIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PNEUMONIA | 2/423 (0.5%) | 2 | 1/429 (0.2%) | 1 | 3/423 (0.7%) | 3 | 1/429 (0.2%) | 1 | 3/617 (0.5%) | 3 | 4/613 (0.7%) | 4 | 1/429 (0.2%) | 1 |
| PNEUMONIA STREPTOCOCCAL | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PYELONEPHRITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| SEPSIS | 0/423 (0%) | 0 | 2/429 (0.5%) | 2 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 2/617 (0.3%) | 2 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| STAPHYLOCOCCAL BACTERAEMIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| STAPHYLOCOCCAL INFECTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| STAPHYLOCOCCAL SEPSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| SUBCUTANEOUS ABSCESS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| URINARY TRACT INFECTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| UROSEPSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| VIRAL INFECTION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| ANKLE FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| COMMINUTED FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| FOOT FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| FOREIGN BODY | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| HAND FRACTURE | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| HUMERUS FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| JOINT DISLOCATION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| TENDON RUPTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| TIBIA FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| UPPER LIMB FRACTURE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| WOUND DEHISCENCE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Investigations | ||||||||||||||
| MUSCLE ENZYME INCREASED | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| WEIGHT INCREASED | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| ARTHRALGIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| BACK PAIN | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| CERVICAL SPINAL STENOSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| INTERVERTEBRAL DISC PROTRUSION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 1/429 (0.2%) | 1 |
| OSTEOARTHRITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 2/423 (0.5%) | 2 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 3/613 (0.5%) | 3 | 3/429 (0.7%) | 4 |
| OSTEONECROSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 2/613 (0.3%) | 2 | 0/429 (0%) | 0 |
| PSORIATIC ARTHROPATHY | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| SPINAL STENOSIS | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| SPONDYLOLISTHESIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| BASAL CELL CARCINOMA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| COLON CANCER METASTATIC | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| LUNG ADENOCARCINOMA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| LUNG CANCER METASTATIC | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| NEUROENDOCRINE CARCINOMA | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| OVARIAN CANCER | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| UTERINE CANCER | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| UTERINE LEIOMYOMA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| ALTERED STATE OF CONSCIOUSNESS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| AMYOTROPHIC LATERAL SCLEROSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| CEREBROVASCULAR ACCIDENT | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| CERVICAL RADICULOPATHY | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| DEMYELINATION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| HEADACHE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| HEPATIC ENCEPHALOPATHY | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| ISCHAEMIC STROKE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| LACUNAR STROKE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| SYNCOPE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| TRANSIENT ISCHAEMIC ATTACK | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Psychiatric disorders | ||||||||||||||
| ANXIETY | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| DEPRESSION | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 2/617 (0.3%) | 2 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| Renal and urinary disorders | ||||||||||||||
| ACUTE KIDNEY INJURY | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| NEPHROLITHIASIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 1/429 (0.2%) | 1 |
| RENAL COLIC | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| URETEROLITHIASIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Reproductive system and breast disorders | ||||||||||||||
| BENIGN PROSTATIC HYPERPLASIA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| FALLOPIAN TUBE CYST | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| FIBROCYSTIC BREAST DISEASE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| HAEMORRHAGIC OVARIAN CYST | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| OVARIAN CYST | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| UTERINE PROLAPSE | 0/423 (0%) | 0 | 1/429 (0.2%) | 2 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 2 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| OBSTRUCTIVE AIRWAYS DISORDER | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| PLEURAL EFFUSION | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| PNEUMOTHORAX SPONTANEOUS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PULMONARY EMBOLISM | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PULMONARY FIBROSIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| RESPIRATORY DISTRESS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| SLEEP APNOEA SYNDROME | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| TONSILLAR HYPERTROPHY | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| ANGIOEDEMA | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 2 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| DERMATITIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| DERMATITIS CONTACT | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| INGROWING NAIL | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 1/617 (0.2%) | 1 | 0/613 (0%) | 0 | 0/429 (0%) | 0 |
| PSORIASIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 1/613 (0.2%) | 1 | 0/429 (0%) | 0 |
| PUSTULAR PSORIASIS | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 0/429 (0%) | 0 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
| Vascular disorders | ||||||||||||||
| DEEP VEIN THROMBOSIS | 1/423 (0.2%) | 1 | 0/429 (0%) | 0 | 0/423 (0%) | 0 | 1/429 (0.2%) | 1 | 0/617 (0%) | 0 | 0/613 (0%) | 0 | 1/429 (0.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Placebo: Week 1-24 | Upadacitinib 15 mg: Week 1-24 | Upadacitinib 30 mg: Week 1-24 | Adalimumab: Week 1-24 | Upadacitinib 15 mg: Week 1-56 | Upadacitinib 30 mg: Week 1-56 | Adalimumab: Week 1-56 | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 121/423 (28.6%) | 159/429 (37.1%) | 176/423 (41.6%) | 143/429 (33.3%) | 305/617 (49.4%) | 327/613 (53.3%) | 189/429 (44.1%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| DIARRHOEA | 10/423 (2.4%) | 10 | 18/429 (4.2%) | 19 | 14/423 (3.3%) | 16 | 9/429 (2.1%) | 10 | 30/617 (4.9%) | 32 | 34/613 (5.5%) | 37 | 19/429 (4.4%) | 21 |
| Infections and infestations | ||||||||||||||
| BRONCHITIS | 10/423 (2.4%) | 10 | 14/429 (3.3%) | 16 | 19/423 (4.5%) | 22 | 9/429 (2.1%) | 9 | 40/617 (6.5%) | 43 | 37/613 (6%) | 43 | 13/429 (3%) | 14 |
| NASOPHARYNGITIS | 21/423 (5%) | 24 | 21/429 (4.9%) | 25 | 26/423 (6.1%) | 29 | 29/429 (6.8%) | 33 | 54/617 (8.8%) | 74 | 67/613 (10.9%) | 79 | 41/429 (9.6%) | 54 |
| ORAL HERPES | 4/423 (0.9%) | 4 | 7/429 (1.6%) | 9 | 19/423 (4.5%) | 26 | 6/429 (1.4%) | 7 | 15/617 (2.4%) | 18 | 31/613 (5.1%) | 47 | 10/429 (2.3%) | 14 |
| UPPER RESPIRATORY TRACT INFECTION | 34/423 (8%) | 37 | 45/429 (10.5%) | 51 | 40/423 (9.5%) | 45 | 30/429 (7%) | 34 | 88/617 (14.3%) | 121 | 97/613 (15.8%) | 131 | 52/429 (12.1%) | 62 |
| URINARY TRACT INFECTION | 10/423 (2.4%) | 10 | 18/429 (4.2%) | 20 | 16/423 (3.8%) | 19 | 14/429 (3.3%) | 15 | 38/617 (6.2%) | 51 | 41/613 (6.7%) | 58 | 18/429 (4.2%) | 21 |
| Investigations | ||||||||||||||
| ALANINE AMINOTRANSFERASE INCREASED | 12/423 (2.8%) | 14 | 18/429 (4.2%) | 22 | 27/423 (6.4%) | 30 | 32/429 (7.5%) | 35 | 41/617 (6.6%) | 58 | 48/613 (7.8%) | 58 | 40/429 (9.3%) | 49 |
| ASPARTATE AMINOTRANSFERASE INCREASED | 8/423 (1.9%) | 9 | 13/429 (3%) | 15 | 15/423 (3.5%) | 18 | 22/429 (5.1%) | 23 | 31/617 (5%) | 37 | 37/613 (6%) | 43 | 26/429 (6.1%) | 31 |
| BLOOD CREATINE PHOSPHOKINASE INCREASED | 6/423 (1.4%) | 7 | 38/429 (8.9%) | 42 | 42/423 (9.9%) | 51 | 24/429 (5.6%) | 24 | 62/617 (10%) | 81 | 84/613 (13.7%) | 116 | 30/429 (7%) | 38 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| PSORIATIC ARTHROPATHY | 12/423 (2.8%) | 13 | 4/429 (0.9%) | 5 | 8/423 (1.9%) | 8 | 5/429 (1.2%) | 5 | 21/617 (3.4%) | 24 | 31/613 (5.1%) | 31 | 18/429 (4.2%) | 20 |
| Nervous system disorders | ||||||||||||||
| HEADACHE | 10/423 (2.4%) | 10 | 18/429 (4.2%) | 24 | 17/423 (4%) | 19 | 17/429 (4%) | 18 | 30/617 (4.9%) | 43 | 27/613 (4.4%) | 34 | 25/429 (5.8%) | 26 |
| Vascular disorders | ||||||||||||||
| HYPERTENSION | 10/423 (2.4%) | 10 | 17/429 (4%) | 19 | 12/423 (2.8%) | 12 | 7/429 (1.6%) | 7 | 36/617 (5.8%) | 41 | 25/613 (4.1%) | 27 | 14/429 (3.3%) | 14 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
| abbvieclinicaltrials@abbvie.com |
Responsible Party:
AbbVie
ClinicalTrials.gov Identifier:
NCT03104400
Other Study ID Numbers:
- M15-572
- 2016-004130-24
First Posted:
Apr 7, 2017
Last Update Posted:
Jan 25, 2022
Last Verified:
Dec 1, 2021