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SELECT-NEXT: A Study Comparing Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis on a Stable Dose of Conventional Synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs) Who Have an Inadequate Response to csDMARDs Alone

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02675426
Collaborator
(none)
661
Enrollment
167
Locations
4
Arms
74.7
Actual Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are to compare the efficacy, safety, and tolerability of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This Phase 3 multicenter study included two periods. Period 1 was a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib 30 mg once daily and 15 mg once daily versus placebo for the treatment of signs and symptoms of adults with moderately to severely active rheumatoid arthritis (RA) who were on a stable dose of csDMARDs and had an inadequate response to csDMARDs.

Period 2 is a blinded long-term (up to 5 years) extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 30 mg once daily and 15 mg daily in participants who had completed Period 1 that is currently ongoing.

Participants were to be randomized in a 2:2:1:1 ratio using interactive response technology (IRT) to receive double-blind study drug in one of the following treatment groups:

  • Group 1: Upadacitinib 30 mg QD in Period 1 → Upadacitinib 30 mg QD in Period 2

  • Group 2: Upadacitinib 15 mg QD in Period 1 → Upadacitinib 15 mg QD in Period 2

  • Group 3: Placebo in Period 1 → Upadacitinib 30 mg QD in Period 2

  • Group 4: Placebo in Period 1 → Upadacitinib 15 mg QD in Period 2

Randomization was stratified by prior exposure to biological disease-modifying anti-rheumatic drug (bDMARD) (yes/no) and geographic region.

Study Design

Study Type:
Interventional
Actual Enrollment :
661 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 in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs
Actual Study Start Date :
Dec 17, 2015
Actual Primary Completion Date :
Apr 21, 2017
Actual Study Completion Date :
Mar 10, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Upadacitinib 15 mg

Period 1: Participants receive Upadacitinib 15 mg once daily for 12 weeks. Period 2: Participants will continue on Upadacitinib 15 mg once daily.

Drug: Upadacitinib
Tablet; Oral
Other Names:
  • ABT-494
  • Rinvoq

    		•
    Experimental: Upadacitinib 30 mg

    Period 1: Participants receive Upadacitinib 30 mg once daily for 12 weeks. Period 2: Participants will continue on Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.

    Drug: Upadacitinib
    Tablet; Oral
    Other Names:
  • ABT-494
  • Rinvoq

    		•
    Experimental: Placebo and Upadacitinib 15 mg

    Period 1: Participants receive Placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 15 mg once daily.

    Drug: Placebo
    Tablet; Oral

    Drug: Upadacitinib
    Tablet; Oral
    Other Names:
  • ABT-494
  • Rinvoq

    		•
    Experimental: Placebo and Upadacitinib 30 mg

    Period 1: Participants receive Placebo once daily for 12 weeks. Period 2: Participants will receive Upadacitinib 30 mg once daily until participants begin to receive Upadacitinib 15 mg once daily.

    Drug: Placebo
    Tablet; Oral

    Drug: Upadacitinib
    Tablet; Oral
    Other Names:
  • ABT-494
  • Rinvoq

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [Baseline and week 12]

      The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at 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).

    2. Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 [Week 12]

      The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.

    Secondary Outcome Measures

    1. Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 [Baseline and week 12]

      The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.

    2. 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.

    3. 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.

    4. Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12 [Week 12]

      Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6. DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

    5. Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 [Week 12]

      Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

    6. Change From Baseline in Duration of Morning Stiffness at Week 12 [Baseline and week 12]

      Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.

    7. Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) [Baseline and week 12]

      The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from baseline indicates improvement.

    8. 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).

    9. 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).

    10. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 [Baseline and week 1]

      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 to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Adult male or female, at least 18 years old.

    • Diagnosis of Rheumatoid Arthritis (RA) for greater than or equal to 3 months.

    • Subjects have been receiving conventional synthetic DMARD (csDMARD) therapy for greater than or equal to 3 months and on a stable dose for greater than or equal to 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: Methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.

    • Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

    • Subjects with prior exposure to at most one biologic DMARD (bDMARD) may be enrolled (up to 20% of study population) if they have documented evidence of intolerance to bDMARDs or limited exposure (less than 3 months) and have satisfied required washout periods.

    Exclusion Criteria:

    • Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).

    • History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.

    • Subjects who are considered inadequate responders to bDMARD therapy as determined by the Investigator.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 AZ Arthritis and Rheum Assoc /ID# 148651 Mesa Arizona United States 85202
    2 SunValley Arthritis Center, Lt /ID# 140452 Peoria Arizona United States 85381
    3 AZ Arthritis and Rheum Researc /ID# 138500 Phoenix Arizona United States 85032-9306
    4 AZ Arthritis and Rheum Researc /ID# 139286 Phoenix Arizona United States 85032-9306
    5 AZ Arthritis & Rheuma Research /ID# 138598 Phoenix Arizona United States 85032
    6 Arizona Research Center, Inc. /ID# 140448 Phoenix Arizona United States 85053-4061
    7 University of Arizona Cancer Center - North Campus /ID# 140451 Tucson Arizona United States 85719-1478
    8 Covina Arthritis Clinic /ID# 139881 Covina California United States 91722
    9 T. Joseph Raoof, MD, Inc. /ID# 140964 Encino California United States 91436
    10 Allergy and Rheum Med Clin /ID# 146082 La Jolla California United States 92037
    11 Pacific Arthritis Ctr Med Grp /ID# 138744 Los Angeles California United States 90045
    12 Robin K. Dore MD, Inc /ID# 138688 Tustin California United States 92780
    13 Inland Rheum Clin Trials Inc. /ID# 138853 Upland California United States 91786
    14 Denver Arthritis Clinic /ID# 139876 Denver Colorado United States 80230
    15 Clinical Res of West FL, Inc. /ID# 138854 Clearwater Florida United States 33765
    16 Ctr Arthritis & Rheumatic Dise /ID# 141696 Miami Florida United States 33173
    17 Medallion Clinical Research Institute, LLC /ID# 140074 Naples Florida United States 34102
    18 Suncoast Clinical Research /ID# 138633 New Port Richey Florida United States 34652
    19 Omega Research Consultants /ID# 139877 Orlando Florida United States 32810
    20 Arthritis Center, Inc. /ID# 141363 Palm Harbor Florida United States 34684
    21 Institute of Arthritis Res /ID# 138548 Idaho Falls Idaho United States 83404
    22 OrthoIllinois /ID# 139695 Rockford Illinois United States 61114-4937
    23 Clinical Investigation Special /ID# 139696 Skokie Illinois United States 60076
    24 Springfield Clinic /ID# 138602 Springfield Illinois United States 62702-3749
    25 Deerbrook Medical Associates /ID# 139694 Vernon Hills Illinois United States 60061
    26 Indiana Univ School of Med /ID# 140077 Indianapolis Indiana United States 46202
    27 Bluegrass Community Research /ID# 138295 Lexington Kentucky United States 40515
    28 Four Rivers Clinical Research /ID# 141134 Paducah Kentucky United States 42003
    29 MMP Women's Health /ID# 141542 Portland Maine United States 04102
    30 The Center for Rheumatology & /ID# 139203 Wheaton Maryland United States 20902
    31 Mansfield Health Center /ID# 141357 Mansfield Massachusetts United States 02048
    32 Advanced Rheumatology, PC /ID# 140071 Lansing Michigan United States 48910
    33 Justus J. Fiechtner, MD, PC /ID# 138697 Lansing Michigan United States 48910
    34 Physician Res. Collaboration /ID# 138533 Lincoln Nebraska United States 68516
    35 Westroads Clinical Research /ID# 138304 Omaha Nebraska United States 68114
    36 The Center for Rheumatology /ID# 138746 Albany New York United States 12206
    37 PMG Research of Salisbury /ID# 141023 Salisbury North Carolina United States 28144
    38 PMG Research of Wilmington LLC /ID# 140951 Wilmington North Carolina United States 28401
    39 Cincinnati Rheumatic Disease Study Group, Inc. /ID# 138868 Cincinnati Ohio United States 45242-4468
    40 Arthritis Assoc of NW Ohio /ID# 140953 Toledo Ohio United States 43606
    41 Health Research Oklahoma /ID# 138535 Oklahoma City Oklahoma United States 73103-2400
    42 Altoona Ctr Clinical Res /ID# 138741 Duncansville Pennsylvania United States 16635
    43 Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 138689 Summerville South Carolina United States 29486-7887
    44 Comprehensive Arthritis Care, a division of Comprehensive Rheumatology Care PLLC /ID# 141021 Hendersonville Tennessee United States 37075-6213
    45 Tekton Research, Inc. /ID# 141428 Austin Texas United States 78745
    46 Trinity Universal Res Assoc /ID# 149271 Carrollton Texas United States 75007
    47 Arth and Osteo Clin Brazo Valley /ID# 147809 College Station Texas United States 77845
    48 Metroplex Clinical Research /ID# 138698 Dallas Texas United States 75231
    49 Baylor College of Medicine /ID# 138682 Houston Texas United States 77030-3411
    50 Houston Institute for Clin Res /ID# 138716 Houston Texas United States 77074
    51 Arthritis Consultants, P.A. /ID# 141138 Killeen Texas United States 76549
    52 Trinity Universal Research Association /ID# 148649 Plano Texas United States 75024-5283
    53 Accurate Clinical Management /ID# 139338 San Antonio Texas United States 78229
    54 Arthritis & Osteoporosis Clinic /ID# 138703 Waco Texas United States 76710
    55 Western Washington Arthritis C /ID# 138728 Bothell Washington United States 98021
    56 Arthritis Northwest, PLLC /ID# 138539 Spokane Washington United States 99204
    57 Aurora Rheumatology and Immunotherapy Center /ID# 139306 Franklin Wisconsin United States 53132
    58 Mautalen Salud e Investigacion /ID# 141419 Buenos Aires Argentina 1128
    59 Inst. Rheumatologic Strusberg /ID# 145648 Cordoba Argentina 5000
    60 Coffs Clinical Trials /ID# 138747 Coffs Harbour New South Wales Australia 2450
    61 Optimus Clinical Research Pty. /ID# 138769 Kogarah New South Wales Australia 2217
    62 Emeritus Research /ID# 138773 Camberwell Victoria Australia 3124
    63 Barwon Rheumatology /ID# 138772 Geelong Victoria Australia 3220
    64 Rheuma Zentrum Favoriten GmbH /ID# 138787 Vienna Austria 1100
    65 Wilhelminenspital der Stadt Wien /ID# 138788 Wien Austria 1160
    66 Rhumaconsult SPRL /ID# 138813 Charleroi Hainaut Belgium 6000
    67 UZ Gent /ID# 138806 Gent Oost-Vlaanderen Belgium 9000
    68 AZ Sint Lucas /ID# 141338 Brugge Belgium 8310
    69 University Clinical Centre of the Republic of Srpska /ID# 138819 Banja Luka Republika Srpska Bosnia and Herzegovina 78000
    70 University Clinical Centre of the Republic of Srpska /ID# 140372 Banja Luka Republika Srpska Bosnia and Herzegovina 78000
    71 Diag Consult Ctr 17 Sofia EOOD /ID# 141006 Sofia Bulgaria 1505
    72 Diagnostic Consultative Center /ID# 138882 Sofia Bulgaria 1612
    73 Manitoba Clinic /ID# 139086 Winnipeg Manitoba Canada R3A IM3
    74 Eastern Health /ID# 140431 St. John's Newfoundland and Labrador Canada A1B 3V6
    75 Groupe de Recherche en Maladies Osseuses /ID# 138906 Sainte-foy Quebec Canada G1V 3M7
    76 Dr. Latha Naik /ID# 139089 Saskatoon Saskatchewan Canada S7K 3H3
    77 Klinicki bolnicki centar Rijeka /ID# 138649 Rijeka Primorsko-goranska Zupanija Croatia 51000
    78 Klinicka bolnica Sveti Duh /ID# 152812 Zagreb Croatia 10000
    79 Medical Center Kuna-Peric /ID# 140365 Zagreb Croatia 10000
    80 Poliklinika Bonifarm /ID# 141415 Zagreb Croatia 10000
    81 L.K.N. Arthrocentrum, s.r.o /ID# 141340 Hlučín Moravskoslezsky Kraj Czechia 748 01
    82 Revmatologie, s.r.o. /ID# 138899 Brno Czechia 638 00
    83 Artroscan s.r.o. /ID# 138833 Ostrava Czechia 722 00
    84 Nemocnice Slany /ID# 141112 Slany Czechia 274 01
    85 PV-MEDICAL s.r.o. /ID# 138913 Zlin Czechia 760 01
    86 Center of Clinical and Basic Research /ID# 141116 Tallinn Harjumaa Estonia 10128
    87 Paernu Hospital /ID# 138961 Pärnu Estonia 80010
    88 East Tallinn Central Hospital /ID# 140618 Tallinn Estonia 10138
    89 Helsinki Univ Central Hospital /ID# 140381 Helsinki Finland 00290
    90 Kiljava Medical Research /ID# 139260 Hyvinkaa Finland 05800
    91 South Karelia Central Hospital /ID# 139973 Lappeenranta Finland 53130
    92 Hopital Saint Joseph /ID# 149188 Marseille CEDEX 08 Bouches-du-Rhone France 13285
    93 CHRU Tours - Hopital Trousseau /ID# 138969 Chambray Les Tours France 37170
    94 Uniklinik Koln /ID# 139084 Köln Nordrhein-Westfalen Germany 50937
    95 Charité Universitätsmedizin Campus Mitte /ID# 139052 Berlin Germany 10117
    96 Immanuel-Krankenhaus /ID# 139059 Berlin Germany 13125
    97 Asklepios Klinik Altona /ID# 140466 Hamburg Germany 22763
    98 Welcker, Planegg, DE /ID# 140467 Planegg Germany 82152
    99 University General Hospital of Heraklion "PA.G.N.I" /ID# 139115 Heraklion Greece 71110
    100 Prince of Wales Hospital /ID# 139314 Sha Tin Hong Kong
    101 Revita Reumatologiai Rendelo /ID# 140761 Budapest Hungary 1027
    102 Fejer Megyei Szent Gyorgy Korh /ID# 138554 Szekesfehervar Hungary 8000
    103 St Vincent's University Hosp /ID# 138562 Dublin Ireland D04 T6F4
    104 Universita di Catanzaro Magna Graecia /ID# 139316 Catanzaro Calabria Italy 88100
    105 JSC Nat Scientific Med Res Ctr /ID# 140575 Astana Kazakhstan 010009
    106 Inha University Hospital /ID# 149310 Incheon Gwang Yeogsi Korea, Republic of 22332
    107 Ajou University Hospital /ID# 149311 Suwon-si Gyeonggido Korea, Republic of 16499
    108 Chonnam National University Hospital /ID# 138651 Gwangju Jeonranamdo Korea, Republic of 61469
    109 Hanyang University Seoul Hospi /ID# 138655 Seoul Seongdong-gu Korea, Republic of 04763
    110 Cath Univ Seoul St Mary's Hosp /ID# 138652 Seoul Seoul Teugbyeolsi Korea, Republic of 06591
    111 Daegu Catholic University Med /ID# 139249 Daegu Korea, Republic of 705-718
    112 Chungnam National University Hospital /ID# 138653 Daejeon Korea, Republic of 35015
    113 Seoul National University Hospital /ID# 138659 Seoul Korea, Republic of 03080
    114 Asan Medical Center /ID# 140579 Seoul Korea, Republic of 05505
    115 LTD M+M Centers /ID# 138818 Adazi Latvia 2164
    116 Klaipeda University Hospital /ID# 141416 Klaipeda Lithuania 92288
    117 Vilnius University Hospital /ID# 141348 Vilnius Lithuania LT-08661
    118 Centro Peninsular de Investigación Clínica SCP /ID# 148160 Colonia Centro Yucatan Mexico 97000
    119 Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 138841 Mexico City Mexico 06090
    120 Porter Rheumatology Ltd /ID# 138347 Nelson New Zealand 7010
    121 NZOZ Nasz Lekarz /ID# 138374 Toruń Kujawsko-pomorskie Poland 87-100
    122 McBk Sc /Id# 138360 Grodzisk Mazowiecki Mazowieckie Poland 05-825
    123 Osteo-Medic spolka cywilna /ID# 138371 Białystok Podlaskie Poland 15-351
    124 NZOZ Centrum Reumatologiczne /ID# 138353 Elblag Warminsko-mazurskie Poland 82-300
    125 Rheuma Medicus /ID# 138372 Warsaw Poland 02-118
    126 Instituto Portugues De Reumatologia /ID# 148315 Lisbon Lisboa Portugal 1050-034
    127 Centro Hospitalar Lisboa Ocidental, EPE /ID# 140594 Lisbon Lisboa Portugal 1349-019
    128 School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 139328 San Juan Puerto Rico 00935
    129 Spitalul Clinic Judetean de Urgenta /ID# 138407 Cluj Romania 400006
    130 Spitalul Municipal Ploiesti /ID# 138405 Ploiesti Romania 100337
    131 Spitalul Clinic Judetean de Ur /ID# 138393 Sibiu Romania 550245
    132 LLC Novaya Klinika /ID# 139269 Pyatigorsk Stavropol Skiy Kray Russian Federation 357500
    133 Kazan State Medical University /ID# 138413 Kazan Tatarstan, Respublika Russian Federation 420012
    134 Republican Clin Hos n.a. Baran /ID# 139273 Petrozavodsk Russian Federation 185019
    135 Samara Regional Clinical Hosp /ID# 148642 Samara Russian Federation 443095
    136 Ulyanovsk Regional Clin Hosp /ID# 139279 Ulyanovsk Russian Federation 432018
    137 Voronezh State Medical Univers /ID# 148431 Voronezh Russian Federation 394036
    138 Yaroslavi State Medical Univer /ID# 139908 Yaroslavl Russian Federation 150000
    139 ARTROMAC n.o. /ID# 138428 Kosice Slovakia 040 11
    140 Nemocnica Kosice Saca, a.s. /ID# 138918 Kosice Slovakia 040 15
    141 Slovak research center Team Member, Thermium s.r.o. /ID# 139924 Pieštany Slovakia 921 01
    142 Narodny ustav reumatickych chorob Piestany /ID# 138427 Pieštany Slovakia 921 12
    143 REUMA-GLOBAL, s.r.o. /ID# 139912 Trnava Slovakia 91701
    144 St. Augustine's Medical Centre /ID# 141352 Berea Kwazulu-Natal South Africa NL 4001
    145 Arthritis Clinical Research Tr /ID# 138945 Cape Town Western Cape South Africa 7405
    146 Winelands Medical Research Ctr /ID# 138944 Stellenbosch Western Cape South Africa 7600
    147 Hospital Regional de Malaga /ID# 138975 Málaga Malaga Spain 29009
    148 Hospital General Univ de Elche /ID# 138991 Elche Spain 03202
    149 Hospital Clin Univ San Carlos /ID# 138993 Madrid Spain 28040
    150 Hosp Nuestra Senora Esperanza /ID# 138997 Santiago de Compostela Spain 15705
    151 HFR Fribourg - Hopital Canton /ID# 139155 Fribourg Switzerland 1708
    152 China Medical University Hosp /ID# 139232 Taichung City Taichung Taiwan 40447
    153 National Cheng Kung University Hospital /ID# 140868 Tainan City Tainan Taiwan 70403
    154 National Taiwan Univ Hosp /ID# 141443 Taipei City Taipei Taiwan 10002
    155 Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 140869 Kaohsiung Taiwan 80708
    156 Far Eastern Memorial Hospital /ID# 140871 New Taipei City Taiwan 22060
    157 Taipei Veterans General Hosp /ID# 139234 Taipei City Taiwan 11217
    158 Ankara Numune Training and Res /ID# 139237 Ankara Turkey 06100
    159 LLC Revmocentr /ID# 139872 Kyiv Ukraine 04070
    160 MNCE "Lviv City Clinical Hospital #4" /ID# 139873 Lviv Ukraine 79007
    161 Odessa National Medical Univ /ID# 139179 Odesa Ukraine 65026
    162 Leicester Royal Infirmary /ID# 139184 Leicester England United Kingdom LE1 5WW
    163 Whipps Cross Univ Hospital /ID# 139523 London London, City Of United Kingdom E11 1NR
    164 The Royal Free Hospital /ID# 139191 London London, City Of United Kingdom NW3 2QG
    165 Western General Hospital /ID# 139524 Edinburgh United Kingdom EH4 2XU
    166 Southampton General Hospital /ID# 139169 Southampton United Kingdom SO16 6YD
    167 Warrington + Halton Hosp NHS /ID# 139195 Warrington United Kingdom WA5 1LZ

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., AbbVie

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02675426
    Other Study ID Numbers:
    • M13-549
    • 2015-003332-13
    First Posted:
    Feb 5, 2016
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022
    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
    Musculoskeletal Disease
    Arthritis
    Joint Disease
    Anti-inflammatory agents
    Antirheumatic agents
    Upadacitinib
    ABT-494
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Upadacitinib

    Study Results

    Participant Flow

    Recruitment Details Participants were randomized at 150 centers in 35 countries in North America, eastern and western Europe, Asia, South America, Australia, New Zealand, and South Africa. The study had a 12-week placebo-controlled, double-blind period (Period 1), and an ongoing 5-year double-blind extension (Period 2). Results for Period 1 are reported.
    Pre-assignment Detail Participants were randomly assigned in a 1:1:1 ratio to 15 or 30 mg upadacitinib or placebo. Randomization was stratified by prior exposure to biologic disease-modifying anti-rheumatic drug (bDMARD) and geographical region. Participants assigned to placebo were switched to 15 or 30 mg upadacitinib at week 12 according to randomization assignment.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Period Title: Overall Study
    STARTED 221 221 219
    Treated 221 221 219
    COMPLETED 208 213 201
    NOT COMPLETED 13 8 18

    Baseline Characteristics

    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg Total
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1. Total of all reporting groups
    Overall Participants 221 221 219 661
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    56.0
    (12.22)
    55.3
    (11.47)
    55.8
    (11.29)
    55.7
    (11.65)
    Age, Customized (Count of Participants)
    < 40 years
    21
    9.5%
    23
    10.4%
    22
    10%
    66
    10%
    40 to 64 years
    145
    65.6%
    153
    69.2%
    145
    66.2%
    443
    67%
    ≥ 65 years
    55
    24.9%
    45
    20.4%
    52
    23.7%
    152
    23%
    Sex: Female, Male (Count of Participants)
    Female
    166
    75.1%
    182
    82.4%
    172
    78.5%
    520
    78.7%
    Male
    55
    24.9%
    39
    17.6%
    47
    21.5%
    141
    21.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    27
    12.2%
    23
    10.4%
    30
    13.7%
    80
    12.1%
    Not Hispanic or Latino
    194
    87.8%
    198
    89.6%
    189
    86.3%
    581
    87.9%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race/Ethnicity, Customized (Count of Participants)
    White
    187
    84.6%
    188
    85.1%
    186
    84.9%
    561
    84.9%
    Black or African American
    10
    4.5%
    13
    5.9%
    8
    3.7%
    31
    4.7%
    American Indian / Alaskan Native
    1
    0.5%
    0
    0%
    1
    0.5%
    2
    0.3%
    Asian
    19
    8.6%
    19
    8.6%
    21
    9.6%
    59
    8.9%
    Multiple
    4
    1.8%
    1
    0.5%
    3
    1.4%
    8
    1.2%
    Geographical Region (Count of Participants)
    North America
    90
    40.7%
    88
    39.8%
    89
    40.6%
    267
    40.4%
    South/Central America
    8
    3.6%
    10
    4.5%
    11
    5%
    29
    4.4%
    Western Europe
    24
    10.9%
    22
    10%
    23
    10.5%
    69
    10.4%
    Eastern Europe
    74
    33.5%
    76
    34.4%
    73
    33.3%
    223
    33.7%
    Asia
    16
    7.2%
    17
    7.7%
    15
    6.8%
    48
    7.3%
    Other
    9
    4.1%
    8
    3.6%
    8
    3.7%
    25
    3.8%
    Prior Biological DMARD Use (Count of Participants)
    Yes
    29
    13.1%
    27
    12.2%
    28
    12.8%
    84
    12.7%
    No
    192
    86.9%
    194
    87.8%
    191
    87.2%
    577
    87.3%
    Duration of Rheumatoid Arthritis (RA) Diagnosis (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    7.2
    (7.45)
    7.3
    (7.89)
    7.3
    (7.86)
    7.3
    (7.72)
    Conventional Synthetic DMARD (csDMARD) Use at Baseline (Count of Participants)
    Methotrexate alone
    141
    63.8%
    122
    55.2%
    136
    62.1%
    399
    60.4%
    Methotrexate and other csDMARD
    49
    22.2%
    47
    21.3%
    39
    17.8%
    135
    20.4%
    csDMARD other than methotrexate
    30
    13.6%
    51
    23.1%
    44
    20.1%
    125
    18.9%
    Missing
    1
    0.5%
    1
    0.5%
    0
    0%
    2
    0.3%
    Tender Joint Count (tender joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [tender joints]
    24.7
    (14.96)
    25.2
    (13.80)
    26.2
    (14.26)
    25.4
    (14.34)
    Swollen Joint Count (swollen joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [swollen joints]
    15.4
    (9.24)
    16.0
    (10.04)
    16.2
    (10.55)
    15.8
    (9.95)
    Patient's Assessment of Pain (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    61.5
    (20.80)
    64.1
    (19.45)
    64.0
    (19.77)
    63.2
    (20.02)
    Patient's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    60.3
    (20.50)
    63.1
    (21.86)
    62.8
    (20.32)
    62.1
    (20.91)
    Physician's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    64.4
    (17.67)
    64.3
    (16.22)
    63.0
    (17.99)
    63.9
    (17.30)
    Health Assessment Questionnaire - Disability Index (HAQ-DI) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    1.4
    (0.63)
    1.5
    (0.61)
    1.5
    (0.61)
    1.5
    (0.62)
    High-sensitivity C-reactive Protein (hsCRP) (mg/L) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/L]
    12.6
    (13.96)
    16.6
    (19.17)
    14.8
    (16.86)
    14.7
    (16.86)
    Disease Activity Score Based on CRP (DAS28 [CRP]) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    5.6
    (0.84)
    5.7
    (0.97)
    5.7
    (0.90)
    5.6
    (0.91)

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
    Description The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at 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).
    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 Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    35.7
    16.2%
    63.8
    28.9%
    66.2
    30.2%
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 28.1
    Confidence Interval (2-Sided) 95%
    19.1 to 37.0
    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 Superiority
    Comments The overall type I error rate of the primary and ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 30.5
    Confidence Interval (2-Sided) 95%
    21.6 to 39.4
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    2. Primary Outcome
    Title Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
    Description The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.
    Time Frame 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 DAS28 data were missing at week 12 were considered non-responders.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    17.2
    7.8%
    48.4
    21.9%
    47.9
    21.9%
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 31.2
    Confidence Interval (2-Sided) 95%
    23.0 to 39.5
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 30.8
    Confidence Interval (2-Sided) 95%
    22.5 to 39.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    3. Secondary Outcome
    Title Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12
    Description The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.
    Time Frame Baseline and week 12

    Outcome Measure Data

    Analysis Population Description
    Full analysis set participants with available data at baseline; multiple imputation was used for missing data.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 220 217 219
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    -1.02
    -2.20
    -2.34
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method ANCOVA
    Comments ANCOVA model with treatment, prior bDMARD use and baseline value as covariates.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.18
    Confidence Interval (2-Sided) 95%
    -1.42 to -0.94
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method ANCOVA
    Comments ANCOVA model with treatment, prior bDMARD use and baseline value as covariates.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -1.32
    Confidence Interval (2-Sided) 95%
    -1.56 to -1.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Difference = Upadacitinib - Placebo
    4. Secondary Outcome
    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 at baseline; multiple imputation was used for missing data.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 220 216 219
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    -0.25
    -0.59
    -0.54
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method ANCOVA
    Comments ANCOVA model with treatment, prior bDMARD use and baseline value as covariates.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.33
    Confidence Interval (2-Sided) 95%
    -0.43 to -0.24
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method ANCOVA
    Comments ANCOVA model with treatment, prior bDMARD use and baseline value as covariates.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -0.28
    Confidence Interval (2-Sided) 95%
    -0.38 to -0.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Difference = Upadacitinib - Placebo
    5. Secondary Outcome
    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 data from observed cases to week 12 was used.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 207 209 197
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    3.03
    7.58
    8.01
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.55
    Confidence Interval (2-Sided) 95%
    3.13 to 5.98
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.98
    Confidence Interval (2-Sided) 95%
    3.54 to 6.42
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Difference = Upadacitinib - Placebo
    6. Secondary Outcome
    Title Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12
    Description Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6. DAS28 (CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
    Time Frame 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 DAS28 (CRP) data were missing at week 12 were considered non-responders.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    10.0
    4.5%
    30.8
    13.9%
    28.3
    12.9%
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 20.8
    Confidence Interval (2-Sided) 95%
    13.6 to 28.1
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 18.4
    Confidence Interval (2-Sided) 95%
    11.2 to 25.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    7. Secondary Outcome
    Title Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
    Description Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
    Time Frame 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 CDAI data were missing at week 12 were considered non-responders.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    19.0
    8.6%
    40.3
    18.2%
    42.0
    19.2%
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 21.3
    Confidence Interval (2-Sided) 95%
    13.0 to 29.5
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 23.0
    Confidence Interval (2-Sided) 95%
    14.7 to 31.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    8. Secondary Outcome
    Title Change From Baseline in Duration of Morning Stiffness at Week 12
    Description Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days.
    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 data from observed cases to week 12 was used.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 202 207 197
    Least Squares Mean (95% Confidence Interval) [minutes]
    -34.27
    -85.28
    -85.13
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value -51.01
    Confidence Interval (2-Sided) 95%
    -78.14 to -23.87
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Treatment Difference
    Estimated Value -50.86
    Confidence Interval (2-Sided) 95%
    -78.19 to -23.53
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Difference = Upadacitinib - Placebo
    9. Secondary Outcome
    Title Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
    Description The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. 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 data from observed cases to week 12 was used.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 207 207 197
    Least Squares Mean (95% Confidence Interval) [units on a scale]
    2.96
    7.91
    7.74
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.95
    Confidence Interval (2-Sided) 95%
    3.31 to 6.60
    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 ranked key secondary endpoints for the two doses was controlled using a graphical multiple testing procedure.
    Statistical Test of Hypothesis p-Value <0.001
    Comments The adjusted p-value under multiplicity control is reported, with significance achieved if the adjusted p-value is less than 0.05.
    Method Mixed Effect Model Repeat Measurement
    Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and baseline value as covariate.
    Method of Estimation Estimation Parameter LS Mean Difference
    Estimated Value 4.78
    Confidence Interval (2-Sided) 95%
    3.12 to 6.44
    Parameter Dispersion Type:
    Value:
    Estimation Comments Treatment Difference = Upadacitinib - Placebo
    10. Secondary Outcome
    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 Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    14.9
    6.7%
    38.0
    17.2%
    43.4
    19.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 23.1
    Confidence Interval (2-Sided) 95%
    15.1 to 31.0
    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 Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 28.4
    Confidence Interval (2-Sided) 95%
    20.4 to 36.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    11. Secondary Outcome
    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 Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    5.9
    2.7%
    20.8
    9.4%
    26.5
    12.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 14.9
    Confidence Interval (2-Sided) 95%
    8.7 to 21.1
    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
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 20.6
    Confidence Interval (2-Sided) 95%
    14.0 to 27.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo
    12. Secondary Outcome
    Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
    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 1

    Outcome Measure Data

    Analysis Population Description
    Full analysis set; participants who prematurely discontinued from study drug prior to week 1 or for whom ACR data were missing at week 1 were considered non-responders.
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants randomized to receive placebo once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
    Measure Participants 221 221 219
    Number (95% Confidence Interval) [percentage of participants]
    8.6
    3.9%
    22.2
    10%
    28.3
    12.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib 15 mg
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use.
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 13.6
    Confidence Interval (2-Sided) 95%
    7.0 to 20.2
    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
    Statistical Test of Hypothesis p-Value <0.001
    Comments Unadjusted p-value
    Method Cochran-Mantel-Haenszel
    Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological disease-modifying anti-rheumatoid drug use
    Method of Estimation Estimation Parameter Response Rate Difference
    Estimated Value 19.7
    Confidence Interval (2-Sided) 95%
    12.7 to 26.7
    Parameter Dispersion Type:
    Value:
    Estimation Comments Response Rate Difference = Upadacitinib - Placebo

    Adverse Events

    Time Frame From the first dose of study drug up to week 12 or up to 30 days after last dose for participants who discontinued study drug prior to week 12.
    Adverse Event Reporting Description
    Arm/Group Title Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Arm/Group Description Participants received placebo once daily for 12 weeks in Period 1. Participants received upadacitinib 15 mg once daily for 12 weeks in Period 1. Participants received upadacitinib 30 mg once daily for 12 weeks in Period 1.
    All Cause Mortality
    Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/221 (0%) 0/221 (0%) 0/219 (0%)
    Serious Adverse Events
    Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/221 (2.3%) 9/221 (4.1%) 6/219 (2.7%)
    Blood and lymphatic system disorders
    LYMPHADENITIS 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    Cardiac disorders
    ATRIAL FIBRILLATION 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    CORONARY ARTERY DISEASE 0/221 (0%) 0 1/221 (0.5%) 1 0/219 (0%) 0
    General disorders
    NON-CARDIAC CHEST PAIN 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    Infections and infestations
    ENTEROCOLITIS INFECTIOUS 0/221 (0%) 0 1/221 (0.5%) 1 0/219 (0%) 0
    PNEUMONIA 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    VARICELLA ZOSTER VIRUS INFECTION 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    VIRAL UPPER RESPIRATORY TRACT INFECTION 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    WOUND INFECTION STAPHYLOCOCCAL 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    Injury, poisoning and procedural complications
    SPINAL COMPRESSION FRACTURE 0/221 (0%) 0 1/221 (0.5%) 1 0/219 (0%) 0
    WRIST FRACTURE 0/221 (0%) 0 2/221 (0.9%) 2 0/219 (0%) 0
    Musculoskeletal and connective tissue disorders
    OSTEOARTHRITIS 0/221 (0%) 0 1/221 (0.5%) 1 1/219 (0.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-CELL SMALL LYMPHOCYTIC LYMPHOMA 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    CHRONIC LYMPHOCYTIC LEUKAEMIA 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    OVARIAN GERM CELL TERATOMA BENIGN 0/221 (0%) 0 1/221 (0.5%) 1 0/219 (0%) 0
    Nervous system disorders
    ISCHAEMIC STROKE 0/221 (0%) 0 0/221 (0%) 0 1/219 (0.5%) 1
    Psychiatric disorders
    SUICIDE ATTEMPT 0/221 (0%) 0 1/221 (0.5%) 1 0/219 (0%) 0
    Renal and urinary disorders
    NEPHROLITHIASIS 0/221 (0%) 0 1/221 (0.5%) 2 0/219 (0%) 0
    Reproductive system and breast disorders
    OVARIAN CYST 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    ORGANISING PNEUMONIA 1/221 (0.5%) 1 0/221 (0%) 0 0/219 (0%) 0
    Other (Not Including Serious) Adverse Events
    Placebo Upadacitinib 15 mg Upadacitinib 30 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 29/221 (13.1%) 41/221 (18.6%) 32/219 (14.6%)
    Gastrointestinal disorders
    NAUSEA 7/221 (3.2%) 8 16/221 (7.2%) 19 3/219 (1.4%) 3
    Infections and infestations
    NASOPHARYNGITIS 9/221 (4.1%) 10 12/221 (5.4%) 13 13/219 (5.9%) 14
    UPPER RESPIRATORY TRACT INFECTION 9/221 (4.1%) 10 12/221 (5.4%) 12 12/219 (5.5%) 13
    Nervous system disorders
    HEADACHE 12/221 (5.4%) 14 9/221 (4.1%) 9 8/219 (3.7%) 9

    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
    Email abbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02675426
    Other Study ID Numbers:
    • M13-549
    • 2015-003332-13
    First Posted:
    Feb 5, 2016
    Last Update Posted:
    Mar 31, 2022
    Last Verified:
    Mar 1, 2022