BALANCE-EXTEND: An Open-label Extension Study Evaluating the Safety and Efficacy of Upadacitinib (ABT-494) in Adults With Rheumatoid Arthritis

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02049138
• Collaborator: (none)
• Enrollment: 493
• Locations: 124
• Arm: 1
• Actual Duration (Months): 90.1
• Patients Per Site: 4
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The primary objective of the study is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in adults with rheumatoid arthritis (RA) who have completed a preceding randomized controlled trial with upadacitinib.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Upadacitinib; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13)	Phase 2

Detailed Description

This is an open-label extension study to assess the long-term safety, tolerability, and efficacy of upadacitinib in adults with RA who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) Phase 2 randomized controlled trial (RCT) with upadacitinib.

All participants received treatment with 6 mg upadacitinib twice a day at the start of the study. Participants may have been up-titrated to 12 mg BID based on protocol-specified criteria. In Protocol Amendment 2 (January 2016) the study treatment was changed to a once daily (QD) formulation. Participants receiving 6 mg BID were transitioned to 15 mg QD and participants receiving 12 mg BID were transitioned to 30 mg QD dosing.

An optional 12-week vaccine sub-study was added in Protocol Amendment 3 (November 2017) to assess the impact of upadacitinib treatment (15 mg QD and 30 mg QD) with background methotrexate on immunological responses to pneumococcal 13-valent conjugate vaccine (PCV-13; Prevnar 13®) in RA patients. The vaccine substudy included 111 participants who were enrolled in the main study, the first participant was enrolled on 13 February 2018 and the the last participant completed the sub-study on 9 April 2020.

In Protocol Amendment 5 (December 2019), the protocol was revised to allow a decrease in upadacitinib dosing from 30 mg QD to 15 mg QD, as appropriate, based on investigator's medical decision or for safety/tolerability concerns.

Study Design

• Study Type: Interventional
• Actual Enrollment: 493 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study, Multicenter, Open-Label Extension (OLE) Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial (RCT) With Upadacitinib (ABT-494)
• Actual Study Start Date: Jan 24, 2014
• Actual Primary Completion Date: Jul 29, 2021
• Actual Study Completion Date: Jul 29, 2021

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Upadacitinib Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). Participants who did not achieve a 20% improvement from RCT Baseline in both Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 6 or Week 12 were up-titrated to 12 mg BID. From January 2017 participants were transitioned to a once-daily (QD) regimen of upadacitinib, either 15 mg QD (participants who were taking 6 mg BID) or 30 mg QD (participants taking 12 mg BID). Starting with Protocol Amendment 5 participants receiving 30 mg QD upadacitinib had the option to decrease the dose to 15 mg QD at the investigator's discretion. A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).

Drug: Upadacitinib; Tablet taken orally; Other Names: ABT-494 RINVOQ® ; Biological: Pneumococcal 13-valent conjugate vaccine (PCV-13); Administered by intramuscular injection; Other Names: Prevnar 13®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   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 With an American College of Rheumatology 50% (ACR50) Response Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   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).

3. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   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).

4. Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination [Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 weeks after vaccination]

   Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).

Secondary Outcome Measures

1. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The 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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. LDA is defined as a DAS28(CRP) score ≤ 3.2.

2. Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The 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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission is defined as a DAS28(CRP) score < 2.6.

3. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. LDA is defined as a CDAI score ≤ 10.

4. Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. Clinical remission is defined as a CDAI score ≤ 2.8.

5. Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. LDA is defined as a SDAI score ≤ 11.0.

6. Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time [Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. Clinical remission is defined as a SDAI score ≤ 3.3.

7. Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores 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.

8. Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. A negative change from Baseline indicates improvement in disease activity.

9. Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

   The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.

10. Change From Baseline in Tender Joint Count (TJC68) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    Sixty-eight joints were assessed by an evaluator for tenderness or pain. The presence of tenderness was scored as a "1" and absence of tenderness as a "0". The total tender joint count is the sum of the scores, and ranges from 0 to 68 (worst).

11. Change From Baseline in Swollen Joint Count (SJC66) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    Sixty-six joints were assessed by an evaluator for swelling. The presence of swelling was scored as a "1" and absence of swelling as a "0". The total swollen joint count is the sum of the scores, and ranges from 0 to 66 (worst).

12. Change From Baseline in Physician's Global Assessment of Disease Activity Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a visual analog scale (VAS) from 0 to 100 mm, where 0 mm indicates no disease activity and 100 mm indicates severe disease activity

13. Change From Baseline in Patient's Global Assessment of Disease Activity Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.

14. Change From Baseline in Patient's Assessment of Pain Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."

15. Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    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.

16. Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

17. Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    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 (4 = not at all fatigued to 0 = very much fatigued). The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.

18. Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    RA-WIS is a tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score < 10 means low risk, scores between 10 and 17 indicate medium risk, and scores > 17 indicate high risk of work instability. A negative change from Baseline indicates improvement in work instability.

19. Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    The EQ-5D-5L is a generic measure of health status consisting of two parts. The first part (the descriptive system) assesses health in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which is rated on 5 levels of severity (1: no problem, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems). A health state index score was calculated from individual health profiles using a UK scoring algorithm. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The higher the score the better the health status. A positive change from baseline indicates improvement in health status.

20. Change From Baseline in EuroQoL-5D VAS Score Over Time [Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312]

    The EQ-5D-5L is a generic measure of health status consisting of two parts. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). A positive change from baseline indicates improvement.

21. Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination [Vaccination Baseline and 12 weeks after vaccination]

    Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).

22. Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination [Vaccination Baseline and 4 and 12 weeks after vaccination]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subjects who have completed Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) with upadacitinib (ABT-494) and did not develop any discontinuation criteria.

2. If the subject has evidence of new latent tuberculosis (TB) infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis before continuing to receive study drug.

3. If female, subject must be postmenopausal, OR permanently surgically sterile, OR for women of childbearing potential practicing at least one protocol-specified method of birth control, that is effective from Study Day 1 through at least 30 days after the last dose of study drug.

4. Subjects must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study specific procedures.

Substudy:

1. Must currently be enrolled in the main study.

2. Must have been receiving a stable dose of upadacitinib (either 15 mg QD or 30 mg QD) for a minimum of 4 weeks prior to the Vaccination visit.

3. Must have been on a stable dose of background methotrexate (no change in dose or frequency) for a minimum of 4 weeks prior to the Vaccination visit.

4. If subject is on corticosteroids, must remain on a stable dose of ≤ 10 mg/day of prednisone or equivalent corticosteroid therapy for at least 4 weeks after the vaccination visit.

5. Must meet the prescribing specifications as per local label requirements to receive Prevnar 13® vaccine.

6. Willing to receive Prevnar13® vaccine.

Exclusion Criteria:

1. Pregnant or breastfeeding female.

2. Ongoing infections at Week 0 that have not been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled but not dosed until the infection has been successfully treated.

3. Anticipated requirement or receipt of any live vaccine during study participation including up to 30 days after the last dose of study drug.

4. Laboratory values from the visit immediately prior to Baseline Visit (local requirements may apply) meeting the following criteria:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 3.0 × upper limit of normal (ULN)

• Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73m^2

• Total white blood cell count (WBC) < 2,000/μL

• Absolute neutrophil count (ANC) < 1,000/μL

• Platelet count < 50,000/μL

• Absolute lymphocytes count < 500/μL

• Hemoglobin < 8 g/dL

1. Enrollment in another interventional clinical study while participating in this study.

2. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive study drug.

Substudy:

1. Receiving any conventional synthetic disease modifying antirheumatic drugs (csDMARDs) other than methotrexate

2. Receiving > 10 mg/day of prednisone or equivalent corticosteroid therapy.

3. Receipt of any steroid injection within 4 weeks prior to Vaccination visit.

4. History of severe allergic reaction (e.g., anaphylaxis) to any component of Prevnar 13®.

5. History of any documented pneumococcal infection within the last 6 months prior to the vaccination visit.

6. Receipt of any vaccine 4 weeks prior to the vaccination visit and/or anticipation of any vaccination for 4 weeks after the vaccination visit.

7. Receipt of any pneumococcal vaccine.

8. Subject is not suitable for the sub-study as per the Investigator's judgment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rheum Assoc of North Alabama /ID# 135926	Huntsville	Alabama	United States	35801
2	AZ Arthritis and Rheumotology Research, PLLC /ID# 135902	Phoenix	Arizona	United States	85032-9306
3	AZ Arthritis and Rheumotology Research, PLLC /ID# 135931	Phoenix	Arizona	United States	85032-9306
4	C.V. Mehta MD, Med Corporation /ID# 124092	Hemet	California	United States	92543
5	Moores Cancer Center at UC San Diego /ID# 128747	La Jolla	California	United States	92093
6	Desert Medical Advances - Palm Desert /ID# 135911	Palm Desert	California	United States	92260
7	Orrin Troum, M.D. and Medical /ID# 135933	Santa Monica	California	United States	90404
8	Duplicate_Robin K. Dore MD, Inc /ID# 135906	Tustin	California	United States	92780
9	Inland Rheum Clin Trials Inc. /ID# 136716	Upland	California	United States	91786
10	Duplicate_Desert Valley Medical Group /ID# 135932	Victorville	California	United States	92395
11	Denver Arthritis Clinic /ID# 135901	Denver	Colorado	United States	80230
12	New England Research Associates, LLC /ID# 124085	Bridgeport	Connecticut	United States	06606-1827
13	Arthritis & Rheumatic Disease Specialties /ID# 135910	Aventura	Florida	United States	33180
14	Rheumatology Associates of South Florida (RASF) - Clinical Research /ID# 124082	Boca Raton	Florida	United States	33486
15	Omega Research Maitland, LLC /ID# 124094	DeBary	Florida	United States	32713-2260
16	University of Florida /ID# 124087	Jacksonville	Florida	United States	32209
17	Suncoast Research Group /ID# 137774	Miami	Florida	United States	33135
18	Omega Research Maitland, LLC /ID# 137398	Orlando	Florida	United States	32808
19	Millennium Research /ID# 135917	Ormond Beach	Florida	United States	32174
20	Arthritis Center, Inc. /ID# 124090	Palm Harbor	Florida	United States	34684
21	IRIS Research and Development, LLC /ID# 140362	Plantation	Florida	United States	33324
22	Lovelace Scientific Resources /ID# 128745	Venice	Florida	United States	34292
23	North Georgia Rheumatology Group /ID# 128746	Lawrenceville	Georgia	United States	30045
24	Kansas City Internal Medicine /ID# 135916	Overland Park	Kansas	United States	66209
25	PRN Professional Research Network of Kansas, LLC /ID# 124091	Wichita	Kansas	United States	67205
26	Klein and Associates MD - Hagerstown /ID# 124086	Hagerstown	Maryland	United States	21742
27	The Center for Rheumatology and Bone Research /ID# 124077	Wheaton	Maryland	United States	20902
28	Clinical Pharmacology Study Group /ID# 124079	Worcester	Massachusetts	United States	01605
29	June DO, PC /ID# 124081	Lansing	Michigan	United States	48910
30	Summit Medical Group /ID# 124076	Clifton	New Jersey	United States	07012-1647
31	Arthritis and Osteoporosis Associates /ID# 135907	Freehold	New Jersey	United States	07728-8307
32	Arthritis Rheumatic and Back Disease Associates. P.A. /ID# 135913	Voorhees	New Jersey	United States	08043
33	Arthritis and Osteo Assoc /ID# 132280	Las Cruces	New Mexico	United States	88011
34	DJL Clinical Research, PLLC /ID# 131936	Charlotte	North Carolina	United States	28210-8508
35	Cincinnati Rheumatic Disease Study Group, Inc. /ID# 135921	Cincinnati	Ohio	United States	45242-4468
36	STAT Research, Inc. /ID# 134906	Vandalia	Ohio	United States	45377-9464
37	Health Research of Oklahoma /ID# 135904	Oklahoma City	Oklahoma	United States	73103-2400
38	Duplicate_East Penn Rheumatology Assoc /ID# 135920	Bethlehem	Pennsylvania	United States	18015
39	Altoona Ctr Clinical Res /ID# 124089	Duncansville	Pennsylvania	United States	16635
40	Emkey Arthritis and Osteoporosis Clinic /ID# 135908	Wyomissing	Pennsylvania	United States	19610
41	Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 124080	Summerville	South Carolina	United States	29486-7887
42	Dr. Ramesh Gupta /ID# 128744	Memphis	Tennessee	United States	38119
43	Austin Rheumatology Research /ID# 124083	Austin	Texas	United States	78705
44	Accurate Clinical Management /ID# 128751	Baytown	Texas	United States	77521
45	Accurate Clinical Management /ID# 128752	Houston	Texas	United States	77004
46	Baylor College of Medicine - Baylor Medical Center /ID# 135905	Houston	Texas	United States	77030-3411
47	Houston Institute for Clin Res /ID# 135912	Houston	Texas	United States	77074
48	Accurate Clinical Research /ID# 128753	Houston	Texas	United States	77089
49	Accurate Clinical Research /ID# 128754	Houston	Texas	United States	77089
50	SW Rheumatology Res. LLC /ID# 135927	Mesquite	Texas	United States	75150
51	Mountain State Clinical Research /ID# 124088	Clarksburg	West Virginia	United States	26301
52	Aurora Rheumatology and Immunotherapy Center /ID# 135922	Franklin	Wisconsin	United States	53132
53	UCL Saint-Luc /ID# 139348	Woluwe-Saint-Lambert	Bruxelles-Capitale	Belgium	1200
54	ReumaClinic Genk-Hasselt /ID# 137775	Genk		Belgium	3600
55	MHAT Trimontsium /ID# 135328	Plovdiv		Bulgaria	4000
56	Duplicate_MHAT Kaspela /ID# 136212	Plovdiv		Bulgaria	4001
57	UHMAT Palmed Plovdiv /ID# 135355	Plovdiv		Bulgaria	4002
58	UMHAT Sveti Ivan Rilski /ID# 135678	Sofia		Bulgaria	1431
59	UMHAT Sveti Ivan Rilski /ID# 136210	Sofia		Bulgaria	1431
60	Diagnostic Consultative Center /ID# 136736	Sofia		Bulgaria	1612
61	Diagnostic consultative center Equita /ID# 136209	Varna		Bulgaria	9000
62	Corporacion de Beneficiencia Osorno /ID# 136189	Osorno	Los Lagos	Chile	1710216
63	Quantum Research /ID# 136188	Puerto Varas	Los Lagos	Chile	5550170
64	Duplicate_Artroscan s.r.o. /ID# 139347	Ostrava		Czechia	722 00
65	L.K.N. Arthrocentrum, s.r.o /ID# 128782	Petrkovice		Czechia	725 29
66	Revmatologicky ustav v Praze /ID# 137937	Praha		Czechia	128 00
67	Revmatologicka ambulance - MUDr. Zuzana Urbanova /ID# 137776	Praha		Czechia	140 00
68	Revmatologie Bruntal, s.r.o /ID# 137782	Prostejov		Czechia	796 01
69	Qualiclinic Kft. /ID# 134170	Budapest	Pest	Hungary	1036
70	Orszagos Reumatologiai es Fizioterapias Intezet /ID# 128785	Budapest		Hungary	1023
71	Szent Margit Szakrendelo /ID# 136676	Budapest		Hungary	1032
72	MAV Korhaz ess Rendelointezet /ID# 139971	Szolnok		Hungary	5000
73	Veszprem Megyei Csolnoky Ferenc Korhaz /ID# 128784	Veszprem		Hungary	8200
74	The Chaim Sheba Medical Center /ID# 139295	Ramat Gan	Tel-Aviv	Israel	5265601
75	Barzilai Medical Center /ID# 140199	Ashkelon		Israel	7830604
76	M & M Centrs LTD /ID# 132439	Adazi		Latvia	LV-2164
77	Arija's Ancane's Family Doctor Practice /ID# 132437	Baldone		Latvia	LV-2125
78	Clinic ORTO /ID# 132438	Riga		Latvia	LV-1005
79	Clinstile, S.A. de C.V. /ID# 137075	Cuauhtemoc	Ciudad De Mexico	Mexico	20313
80	Unidad de Investigacion de las Enfermedades Reumatologicas SA de CV /ID# 137307	Mexico City		Mexico	06090
81	Cliditer SA de CV /ID# 136876	Mexico City		Mexico	06700
82	Timaru Medical Specialists Ltd /ID# 131909	Timaru	Canterbury	New Zealand	7910
83	Waikato Hospital /ID# 131908	Hamilton	Waikato	New Zealand	3240
84	Porter Rheumatology Ltd /ID# 133983	Nelson		New Zealand	7010
85	Reum-Medica S.C. /ID# 128841	Wroclaw	Dolnoslaskie	Poland	50-244
86	Twoja Przychodnia Centrum Medyczne /ID# 128840	Nowa Sol	Lubuskie	Poland	67-100
87	Pratia MCM Krakow /ID# 134749	Krakow	Malopolskie	Poland	30-510
88	NZOZ Lecznica MAK-MED s.c. /ID# 128838	Nadarzyn	Mazowieckie	Poland	05-830
89	Medicome sp. z o.o. /ID# 137397	Oswiecim	Mazowieckie	Poland	32-600
90	Centrum Medyczne Amed Warszawa Zoliborz /ID# 128835	Warsaw	Mazowieckie	Poland	01-518
91	Centrum Medyczne Pratia Warszawa /ID# 136650	Warsaw	Mazowieckie	Poland	01-868
92	Centrum Medyczne Reuma Park w Warszawie /ID# 140198	Warsaw	Mazowieckie	Poland	02-691
93	NBR Polska /ID# 136208	Warszawa	Mazowieckie	Poland	00-465
94	Gabinet Internistyczno-Reumatologiczny /ID# 135876	Bialystok	Podlaskie	Poland	15-077
95	Centrum Medyczne Pratia Gdynia /ID# 137362	Gdynia	Pomorskie	Poland	81-338
96	Ambulatorium Sp. z o.o /ID# 138074	Elblag	Warminsko-mazurskie	Poland	82-300
97	Prywatna Praktyka Lekarska /ID# 128837	Poznan	Wielkopolskie	Poland	61-397
98	Duplicate_REUMED Filia nr 2 /ID# 128839	Lublin		Poland	20-582
99	Dr. Ramon L. Ortega-Colon, MD /ID# 128760	Carolina		Puerto Rico	00983
100	GCM Medical Group PSC - Hato Rey /ID# 128759	San Juan		Puerto Rico	00917-3104
101	Mindful Medical Research /ID# 136211	San Juan		Puerto Rico	00918-3756
102	Kazan State Medical University /ID# 136734	Kazan	Tatarstan, Respublika	Russian Federation	420012
103	Tver Regional Clinical Hospital /ID# 137576	Tver	Tverskaya Oblast	Russian Federation	170036
104	St. Petersburg Research Institute of Emergency Medicine n.а. I. I. Dzhanelidze /ID# 136652	Sankt-Peterburg		Russian Federation	192242
105	MEDMAN s.r.o. /ID# 136649	Martin		Slovakia	036 01
106	Poliklinika Senica n.o. /ID# 134728	Senica		Slovakia	905 01
107	Dr MJ Prins /ID# 138540	Cape Town	Western Cape	South Africa	7500
108	Winelands Medical Research Centre /ID# 134669	Stellenbosch	Western Cape	South Africa	7600
109	Clinica Gaias /ID# 133868	Santiago de Compostela	A Coruna	Spain	15702
110	Hospital General Universitario de Elche /ID# 128851	Elche	Alicante	Spain	03203
111	Hospital Infanta Sofia /ID# 136653	San Sebastián de Los Reyes	Madrid	Spain	28702
112	Hospital Regional de Malaga /ID# 128847	Málaga	Malaga	Spain	29010
113	Hospital Universitario A Coruna - CHUAC /ID# 128846	A Coruna		Spain	15006
114	Hospital CIMA Sanitas /ID# 128849	Barcelona		Spain	08034
115	Hospital Clinico Universitario San Carlos /ID# 128852	Madrid		Spain	28040
116	Hospital Universitario Virgen Macarena /ID# 128853	Sevilla		Spain	41009
117	Hospital QuironSalud Infanta Luisa /ID# 135689	Sevilla		Spain	41010
118	Hospital Universitario Virgen de Valme /ID# 134668	Sevilla		Spain	41014
119	NSC Strazhesko Ist Cardiology /ID# 137330	Kiev		Ukraine	03680
120	Municipal Non-profit Institution Kyiv City Clinical Hospital No. 3 of the Exec /ID# 137334	Kyiv		Ukraine	02125
121	Warrington and Halton Hospitals NHS Foundation Trust /ID# 137514	Warrington	Cheshire West And Chester	United Kingdom	WA5 1QG
122	Barts Health NHS Trust /ID# 135683	London	London, City Of	United Kingdom	E1 2ES
123	West Suffolk Hospital /ID# 128858	Bury St Edmunds	Suffolk	United Kingdom	IP33 2QZ
124	Duplicate_Leeds Teaching Hospitals NHS Trust /ID# 141308	Leeds		United Kingdom	LS9 7TF

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: ABBVIE INC., AbbVie

Study Documents (Full-Text)

• Study Protocol - Dec 1, 2020
• Statistical Analysis Plan - May 3, 2021

More Information

Additional Information:

• Related Info.

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02049138
• Other Study ID Numbers: M13-538; 2013-003530-33
• First Posted: Jan 30, 2014
• Last Update Posted: Jul 12, 2022
• Last Verified: Jun 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 Diseases; Anti-inflammatory Agents; Antirheumatic agents
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Upadacitinib

Study Results

Participant Flow

Recruitment Details

Participants must have completed a preceding rheumatoid arthritis (RA) upadacitinib randomized controlled trial (RCT), Study M13-550 (NCT01960855) or Study M13-537 (NCT02066389) to be enrolled in this long-term extension study. Participants were enrolled at 113 study sites located in 17 countries (Belgium, Bulgaria, Chile, Czechia, Hungary, Israel, Latvia, Mexico, New Zealand, Poland, Russian Federation, Slovakia, South Africa, Spain, United Kingdom, Ukraine, and United States/Puerto Rico).

Pre-assignment Detail

Participants were assigned to upadacitinib 6 mg twice-daily up to 30 days following the Last Visit (Week 12) of the preceding RCT. Participants may have been up-titrated to 12 mg BID and subsequently down-titrated per protocol-specified criteria. Efficacy results are reported by treatment sequence for each participant. Adverse event data are reported according to treatment received at the time of the event. Participants may have enrolled in a vaccine substudy during the main study.

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to a once-daily (QD) dose of 15 mg upadacitinib and remained on this dose throughout the study. A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to a once-daily dose of 30 mg upadacitinib and remained on this dose throughout the study. A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns. A subset of participants who opted-in to the vaccine substudy received a single-dose of 0.5 mL intramuscular injection of pneumococcal 13-valent conjugate vaccine (PCV-13).
Period Title: Overall Study
STARTED	306	149	38
Enrolled in Vaccine Sub-study	76	24	11
COMPLETED	142	51	30
NOT COMPLETED	164	98	8

Baseline Characteristics

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down	Total
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.	Total of all reporting groups
Overall Participants	306	149	38	493
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.8 (12.62)	56.0 (12.56)	53.7 (8.54)	55.7 (12.33)
Age, Customized (Count of Participants)
< 45 years	56 18.3%	30 20.1%	5 13.2%	91 18.5%
45 - < 65 years	174 56.9%	76 51%	28 73.7%	278 56.4%
≥ 65 years	76 24.8%	43 28.9%	5 13.2%	124 25.2%
Sex: Female, Male (Count of Participants)
Female	246 80.4%	117 78.5%	29 76.3%	392 79.5%
Male	60 19.6%	32 21.5%	9 23.7%	101 20.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	76 24.8%	40 26.8%	7 18.4%	123 24.9%
Not Hispanic or Latino	230 75.2%	109 73.2%	31 81.6%	370 75.1%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	293 95.8%	132 88.6%	37 97.4%	462 93.7%
Black or African American	9 2.9%	12 8.1%	1 2.6%	22 4.5%
Asian	1 0.3%	2 1.3%	0 0%	3 0.6%
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	1 0.3%	0 0%	0 0%	1 0.2%
Multiple	2 0.7%	3 2%	0 0%	5 1%
Region (Count of Participants)
Western Europe	27 8.8%	13 8.7%	5 13.2%	45 9.1%
Eastern Europe	144 47.1%	46 30.9%	19 50%	209 42.4%
North America	90 29.4%	78 52.3%	10 26.3%	178 36.1%
South/Central America	42 13.7%	5 3.4%	3 7.9%	50 10.1%
Other	3 1%	7 4.7%	1 2.6%	11 2.2%
Duration of RA (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.34 (8.73)	9.61 (8.36)	7.66 (6.54)	9.29 (8.47)
Tender Joint Count (joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joints]	25.8 (14.49)	30.4 (15.90)	31.3 (15.67)	27.6 (15.17)
Swollen Joint Count (joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joints]	16.7 (10.45)	18.8 (12.03)	19.3 (9.53)	17.5 (10.92)
Physician's Global Assessment of Disease Activity (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	64.4 (15.82)	65.6 (15.41)	65.0 (15.41)	64.8 (15.64)
Patient's Global Assessment of Disease Activity (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	62.4 (20.78)	67.4 (20.52)	66.5 (16.48)	64.2 (20.51)
Patient's Global Assessment of Pain (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	63.8 (19.73)	67.2 (19.64)	66.5 (13.13)	65.0 (19.32)
Health Assessment Questionnaire - Disability Index (HAQ-DI) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]	1.4811 (0.6848)	1.6036 (0.6215)	1.5304 (0.4969)	1.5216 (0.6550)
High-sensitivity reactive Protein (hsCRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	12.8968 (17.8329)	14.9212 (20.1890)	17.1232 (28.1184)	13.8344 (19.5179)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response Over Time
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 (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	87.7 28.7%	73.4 49.3%	77.8 204.7%
Week 12	89.0 29.1%	73.8 49.5%	75.7 199.2%
Week 24	91.8 30%	73.3 49.2%	88.6 233.2%
Week 36	90.2 29.5%	83.2 55.8%	82.9 218.2%
Week 48	90.0 29.4%	82.1 55.1%	88.2 232.1%
Week 60	95.4 31.2%	83.8 56.2%	85.7 225.5%
Week 72	93.0 30.4%	84.2 56.5%	90.6 238.4%
Week 84	94.6 30.9%	76.3 51.2%	96.9 255%
Week 96	92.2 30.1%	86.0 57.7%	90.9 239.2%
Week 108	94.8 31%	85.7 57.5%	87.9 231.3%
Week 120	96.2 31.4%	89.5 60.1%	96.6 254.2%
Week 132	93.9 30.7%	87.5 58.7%	96.7 254.5%
Week 144	94.9 31%	88.0 59.1%	88.9 233.9%
Week 156	92.0 30.1%	87.7 58.9%	92.6 243.7%
Week 168	91.9 30%	88.7 59.5%	82.8 217.9%
Week 180	93.9 30.7%	79.1 53.1%	86.2 226.8%
Week 192	93.5 30.6%	87.1 58.5%	92.9 244.5%
Week 204	94.0 30.7%	81.2 54.5%	86.2 226.8%
Week 216	92.5 30.2%	85.9 57.7%	85.2 224.2%
Week 228	96.0 31.4%	83.6 56.1%	92.9 244.5%
Week 240	92.8 30.3%	85.2 57.2%	89.3 235%
Week 252	94.0 30.7%	87.9 59%	86.7 228.2%
Week 264	93.3 30.5%	81.5 54.7%	89.3 235%
Week 276	93.8 30.7%	84.6 56.8%	81.5 214.5%
Week 288	94.7 30.9%	88.0 59.1%	88.9 233.9%
Week 300	94.4 30.8%	82.0 55%	87.0 228.9%
Week 312	92.2 30.1%	87.8 58.9%	88.5 232.9%

2. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response Over Time
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 (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	63.6 20.8%	37.5 25.2%	48.6 127.9%
Week 12	73.5 24%	41.8 28.1%	45.7 120.3%
Week 24	75.7 24.7%	49.6 33.3%	60.0 157.9%
Week 36	73.5 24%	51.6 34.6%	55.9 147.1%
Week 48	74.2 24.2%	50.0 33.6%	55.6 146.3%
Week 60	79.8 26.1%	52.8 35.4%	65.7 172.9%
Week 72	77.1 25.2%	49.0 32.9%	63.6 167.4%
Week 84	78.8 25.8%	55.8 37.4%	75.8 199.5%
Week 96	74.8 24.4%	53.8 36.1%	63.6 167.4%
Week 108	79.4 25.9%	54.8 36.8%	58.8 154.7%
Week 120	80.7 26.4%	58.0 38.9%	72.4 190.5%
Week 132	79.2 25.9%	56.3 37.8%	69.0 181.6%
Week 144	76.4 25%	65.8 44.2%	60.7 159.7%
Week 156	79.5 26%	63.4 42.6%	76.9 202.4%
Week 168	79.2 25.9%	61.1 41%	75.9 199.7%
Week 180	80.9 26.4%	64.3 43.2%	65.5 172.4%
Week 192	80.7 26.4%	59.4 39.9%	76.9 202.4%
Week 204	82.2 26.9%	59.4 39.9%	79.3 208.7%
Week 216	76.6 25%	55.6 37.3%	66.7 175.5%
Week 228	79.2 25.9%	58.2 39.1%	67.9 178.7%
Week 240	79.6 26%	63.9 42.9%	71.4 187.9%
Week 252	83.8 27.4%	55.2 37%	76.7 201.8%
Week 264	79.7 26%	60.0 40.3%	75.0 197.4%
Week 276	84.5 27.6%	52.9 35.5%	66.7 175.5%
Week 288	82.2 26.9%	58.8 39.5%	61.5 161.8%
Week 300	75.6 24.7%	61.2 41.1%	56.5 148.7%
Week 312	84.3 27.5%	69.4 46.6%	69.2 182.1%

3. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response Over Time
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 (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	38.8 12.7%	15.1 10.1%	21.6 56.8%
Week 12	47.1 15.4%	18.1 12.1%	24.3 63.9%
Week 24	45.5 14.9%	27.6 18.5%	37.1 97.6%
Week 36	49.0 16%	28.3 19%	34.3 90.3%
Week 48	57.1 18.7%	26.7 17.9%	25.0 65.8%
Week 60	60.2 19.7%	30.0 20.1%	42.9 112.9%
Week 72	56.4 18.4%	29.1 19.5%	36.4 95.8%
Week 84	60.3 19.7%	29.5 19.8%	54.5 143.4%
Week 96	57.3 18.7%	34.0 22.8%	42.4 111.6%
Week 108	59.9 19.6%	31.9 21.4%	47.1 123.9%
Week 120	59.4 19.4%	30.7 20.6%	62.1 163.4%
Week 132	61.8 20.2%	33.8 22.7%	48.3 127.1%
Week 144	57.6 18.8%	34.2 23%	39.3 103.4%
Week 156	64.7 21.1%	38.9 26.1%	55.6 146.3%
Week 168	62.9 20.6%	42.3 28.4%	58.6 154.2%
Week 180	59.1 19.3%	29.6 19.9%	48.3 127.1%
Week 192	62.0 20.3%	31.9 21.4%	48.1 126.6%
Week 204	65.0 21.2%	42.6 28.6%	58.6 154.2%
Week 216	59.1 19.3%	41.9 28.1%	46.4 122.1%
Week 228	60.0 19.6%	39.3 26.4%	60.7 159.7%
Week 240	66.2 21.6%	38.7 26%	46.4 122.1%
Week 252	62.9 20.6%	29.3 19.7%	50.0 131.6%
Week 264	58.5 19.1%	37.0 24.8%	57.1 150.3%
Week 276	66.1 21.6%	34.6 23.2%	48.0 126.3%
Week 288	65.9 21.5%	44.2 29.7%	44.4 116.8%
Week 300	60.8 19.9%	41.2 27.7%	43.5 114.5%
Week 312	63.1 20.6%	39.6 26.6%	55.6 146.3%

4. Primary Outcome

Title	Percentage of Participants With Satisfactory Humoral Response to PCV-13 Four Weeks After Vaccination
Description	Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).
Time Frame	Vaccination Baseline (defined as the last non-missing observation on or before the date of receiving PCV-13 vaccination) and 4 weeks after vaccination

Outcome Measure Data

Analysis Population Description

The sub-study full analysis set (FAS) included all participants enrolled in the sub-study who received PCV-13 vaccination and at least 1 dose of upadacitinib 15 mg or 30 mg after vaccination during the sub-study. Analysis includes participants with available data at the Week 4 visit of the sub-study.

Arm/Group Title	Upadacitinib 15 mg + PCV-13	Upadacitinib 30 mg + PCV-13
Arm/Group Description	Participants receiving 15 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).	Participants receiving 30 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).
Measure Participants	83	23
Number (95% Confidence Interval) [percentage of participants]	67.5 22.1%	56.5 37.9%

5. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
Description	The 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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. LDA is defined as a DAS28(CRP) score ≤ 3.2.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	70.3 23%	43.2 29%	43.2 113.7%
Week 12	77.9 25.5%	43.4 29.1%	43.2 113.7%
Week 24	82.4 26.9%	48.5 32.6%	52.8 138.9%
Week 36	80.5 26.3%	50.8 34.1%	55.6 146.3%
Week 48	86.8 28.4%	54.2 36.4%	56.8 149.5%
Week 60	86.2 28.2%	56.4 37.9%	66.7 175.5%
Week 72	84.7 27.7%	51.0 34.2%	69.7 183.4%
Week 84	88.9 29.1%	60.2 40.4%	85.3 224.5%
Week 96	82.4 26.9%	64.9 43.6%	79.4 208.9%
Week 108	88.2 28.8%	66.3 44.5%	70.6 185.8%
Week 120	85.9 28.1%	69.0 46.3%	77.4 203.7%
Week 132	88.6 29%	70.1 47%	87.1 229.2%
Week 144	85.2 27.8%	68.6 46%	82.1 216.1%
Week 156	86.1 28.1%	74.6 50.1%	86.2 226.8%
Week 168	90.0 29.4%	78.3 52.6%	80.0 210.5%
Week 180	90.4 29.5%	69.6 46.7%	80.0 210.5%
Week 192	89.3 29.2%	75.0 50.3%	96.3 253.4%
Week 204	88.6 29%	61.4 41.2%	83.3 219.2%
Week 216	89.9 29.4%	70.3 47.2%	82.1 216.1%
Week 228	89.4 29.2%	70.9 47.6%	86.2 226.8%
Week 240	89.5 29.2%	75.8 50.9%	86.2 226.8%
Week 252	91.7 30%	67.2 45.1%	83.9 220.8%
Week 264	86.2 28.2%	67.9 45.6%	82.1 216.1%
Week 276	91.7 30%	74.1 49.7%	72.0 189.5%
Week 288	90.6 29.6%	71.7 48.1%	76.0 200%
Week 300	94.1 30.8%	67.6 45.4%	80.0 210.5%
Week 312	84.5 27.6%	68.8 46.2%	70.4 185.3%

6. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score-28 (DAS28[CRP]) Over Time
Description	The 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 (measured on a VAS from 0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 (CRP) range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical remission is defined as a DAS28(CRP) score < 2.6.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	53.0 17.3%	21.2 14.2%	29.7 78.2%
Week 12	56.6 18.5%	25.5 17.1%	27.0 71.1%
Week 24	60.8 19.9%	31.3 21%	38.9 102.4%
Week 36	65.0 21.2%	35.2 23.6%	50.0 131.6%
Week 48	66.2 21.6%	36.4 24.4%	35.1 92.4%
Week 60	72.9 23.8%	38.2 25.6%	50.0 131.6%
Week 72	69.0 22.5%	35.6 23.9%	51.5 135.5%
Week 84	72.0 23.5%	36.7 24.6%	52.9 139.2%
Week 96	71.7 23.4%	45.4 30.5%	52.9 139.2%
Week 108	74.4 24.3%	42.4 28.5%	47.1 123.9%
Week 120	74.1 24.2%	49.4 33.2%	45.2 118.9%
Week 132	73.7 24.1%	40.3 27%	61.3 161.3%
Week 144	71.0 23.2%	44.3 29.7%	60.7 159.7%
Week 156	74.7 24.4%	50.7 34%	65.5 172.4%
Week 168	77.5 25.3%	49.3 33.1%	66.7 175.5%
Week 180	75.3 24.6%	44.9 30.1%	56.7 149.2%
Week 192	76.9 25.1%	47.2 31.7%	55.6 146.3%
Week 204	77.1 25.2%	47.1 31.6%	76.7 201.8%
Week 216	79.2 25.9%	56.3 37.8%	53.6 141.1%
Week 228	80.8 26.4%	49.1 33%	69.0 181.6%
Week 240	75.2 24.6%	50.0 33.6%	69.0 181.6%
Week 252	80.7 26.4%	44.8 30.1%	58.1 152.9%
Week 264	73.8 24.1%	39.6 26.6%	67.9 178.7%
Week 276	76.9 25.1%	50.0 33.6%	52.0 136.8%
Week 288	74.5 24.3%	47.8 32.1%	48.0 126.3%
Week 300	75.2 24.6%	43.2 29%	55.0 144.7%
Week 312	72.4 23.7%	45.8 30.7%	63.0 165.8%

7. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Over Time
Description	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. LDA is defined as a CDAI score ≤ 10.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	65.3 21.3%	35.2 23.6%	35.1 92.4%
Week 12	71.1 23.2%	39.7 26.6%	32.4 85.3%
Week 24	80.3 26.2%	46.6 31.3%	51.4 135.3%
Week 36	77.8 25.4%	44.4 29.8%	57.1 150.3%
Week 48	83.0 27.1%	50.8 34.1%	38.9 102.4%
Week 60	85.8 28%	58.9 39.5%	63.9 168.2%
Week 72	85.5 27.9%	46.2 31%	60.6 159.5%
Week 84	84.4 27.6%	52.6 35.3%	75.0 197.4%
Week 96	81.3 26.6%	63.5 42.6%	57.6 151.6%
Week 108	85.1 27.8%	67.4 45.2%	54.5 143.4%
Week 120	87.2 28.5%	67.0 45%	77.4 203.7%
Week 132	87.4 28.6%	72.5 48.7%	76.7 201.8%
Week 144	88.4 28.9%	68.0 45.6%	78.6 206.8%
Week 156	88.8 29%	73.2 49.1%	71.4 187.9%
Week 168	90.8 29.7%	82.2 55.2%	83.3 219.2%
Week 180	88.3 28.9%	73.9 49.6%	76.7 201.8%
Week 192	88.1 28.8%	70.0 47%	79.3 208.7%
Week 204	89.0 29.1%	71.4 47.9%	82.8 217.9%
Week 216	88.6 29%	70.3 47.2%	78.6 206.8%
Week 228	89.3 29.2%	67.9 45.6%	79.3 208.7%
Week 240	87.6 28.6%	72.6 48.7%	75.9 199.7%
Week 252	89.0 29.1%	73.7 49.5%	74.2 195.3%
Week 264	83.5 27.3%	63.0 42.3%	75.9 199.7%
Week 276	87.6 28.6%	67.9 45.6%	67.9 178.7%
Week 288	90.3 29.5%	74.5 50%	75.0 197.4%
Week 300	89.8 29.3%	72.0 48.3%	70.8 186.3%
Week 312	86.6 28.3%	70.2 47.1%	73.1 192.4%

8. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Over Time
Description	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. Clinical remission is defined as a CDAI score ≤ 2.8.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	23.4 7.6%	4.9 3.3%	10.8 28.4%
Week 12	26.4 8.6%	6.4 4.3%	8.8 23.2%
Week 24	28.3 9.2%	12.8 8.6%	14.3 37.6%
Week 36	32.5 10.6%	9.5 6.4%	17.1 45%
Week 48	34.8 11.4%	11.0 7.4%	11.1 29.2%
Week 60	43.1 14.1%	13.1 8.8%	22.2 58.4%
Week 72	43.5 14.2%	12.5 8.4%	9.1 23.9%
Week 84	43.4 14.2%	12.4 8.3%	18.8 49.5%
Week 96	40.4 13.2%	15.6 10.5%	21.2 55.8%
Week 108	44.8 14.6%	16.3 10.9%	18.2 47.9%
Week 120	43.6 14.2%	12.5 8.4%	22.6 59.5%
Week 132	46.7 15.3%	18.8 12.6%	33.3 87.6%
Week 144	38.1 12.5%	14.7 9.9%	28.6 75.3%
Week 156	47.2 15.4%	14.1 9.5%	32.1 84.5%
Week 168	48.6 15.9%	20.5 13.8%	33.3 87.6%
Week 180	48.0 15.7%	15.9 10.7%	20.0 52.6%
Week 192	46.4 15.2%	18.6 12.5%	24.1 63.4%
Week 204	51.2 16.7%	20.0 13.4%	34.5 90.8%
Week 216	46.2 15.1%	21.9 14.7%	28.6 75.3%
Week 228	44.3 14.5%	25.0 16.8%	31.0 81.6%
Week 240	51.6 16.9%	24.2 16.2%	31.0 81.6%
Week 252	52.7 17.2%	19.3 13%	22.6 59.5%
Week 264	48.1 15.7%	20.4 13.7%	17.2 45.3%
Week 276	53.5 17.5%	24.5 16.4%	28.6 75.3%
Week 288	51.5 16.8%	25.5 17.1%	28.6 75.3%
Week 300	51.2 16.7%	22.0 14.8%	29.2 76.8%
Week 312	50.4 16.5%	27.7 18.6%	34.6 91.1%

9. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Simplified Disease Activity Index (SDAI) Over Time
Description	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. LDA is defined as a SDAI score ≤ 11.0.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	54.2 17.7%	25.4 17%	32.4 85.3%
Week 12	61.1 20%	33.3 22.3%	23.5 61.8%
Week 24	66.8 21.8%	33.1 22.2%	48.6 127.9%
Week 36	67.8 22.2%	34.9 23.4%	48.6 127.9%
Week 48	73.7 24.1%	38.1 25.6%	41.7 109.7%
Week 60	72.9 23.8%	41.1 27.6%	61.1 160.8%
Week 72	71.5 23.4%	36.5 24.5%	51.5 135.5%
Week 84	74.6 24.4%	40.2 27%	62.5 164.5%
Week 96	71.2 23.3%	45.8 30.7%	51.5 135.5%
Week 108	75.8 24.8%	51.2 34.4%	54.5 143.4%
Week 120	74.6 24.4%	55.2 37%	64.5 169.7%
Week 132	77.7 25.4%	43.4 29.1%	66.7 175.5%
Week 144	70.7 23.1%	44.3 29.7%	67.9 178.7%
Week 156	75.0 24.5%	58.5 39.3%	64.3 169.2%
Week 168	75.8 24.8%	59.4 39.9%	66.7 175.5%
Week 180	78.7 25.7%	55.9 37.5%	53.3 140.3%
Week 192	76.2 24.9%	52.9 35.5%	66.7 175.5%
Week 204	71.3 23.3%	52.9 35.5%	79.3 208.7%
Week 216	79.0 25.8%	56.3 37.8%	57.1 150.3%
Week 228	77.2 25.2%	56.4 37.9%	69.0 181.6%
Week 240	74.5 24.3%	50.0 33.6%	69.0 181.6%
Week 252	79.0 25.8%	52.6 35.3%	61.3 161.3%
Week 264	71.1 23.2%	51.9 34.8%	67.9 178.7%
Week 276	78.5 25.7%	56.6 38%	56.0 147.4%
Week 288	74.5 24.3%	56.5 37.9%	68.0 178.9%
Week 300	78.2 25.6%	50.0 33.6%	63.2 166.3%
Week 312	72.1 23.6%	48.9 32.8%	65.4 172.1%

10. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission (CR) Based on Simplified Disease Activity Index (SDAI) Over Time
Description	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. Clinical remission is defined as a SDAI score ≤ 3.3.
Time Frame	Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	15.0 4.9%	4.2 2.8%	2.7 7.1%
Week 12	17.8 5.8%	2.8 1.9%	5.9 15.5%
Week 24	18.2 5.9%	6.0 4%	11.4 30%
Week 36	23.6 7.7%	4.0 2.7%	8.6 22.6%
Week 48	25.9 8.5%	7.6 5.1%	8.3 21.8%
Week 60	32.6 10.7%	12.1 8.1%	13.9 36.6%
Week 72	31.0 10.1%	9.6 6.4%	9.1 23.9%
Week 84	32.2 10.5%	8.2 5.5%	12.5 32.9%
Week 96	28.8 9.4%	13.5 9.1%	18.2 47.9%
Week 108	31.4 10.3%	10.5 7%	12.1 31.8%
Week 120	33.5 10.9%	8.0 5.4%	12.9 33.9%
Week 132	33.1 10.8%	10.5 7%	20.0 52.6%
Week 144	26.3 8.6%	5.7 3.8%	14.3 37.6%
Week 156	33.5 10.9%	7.7 5.2%	28.6 75.3%
Week 168	31.8 10.4%	11.6 7.8%	26.7 70.3%
Week 180	33.1 10.8%	10.3 6.9%	13.3 35%
Week 192	32.7 10.7%	12.9 8.7%	14.8 38.9%
Week 204	37.2 12.2%	11.4 7.7%	24.1 63.4%
Week 216	32.5 10.6%	10.9 7.3%	10.7 28.2%
Week 228	30.9 10.1%	16.4 11%	24.1 63.4%
Week 240	34.0 11.1%	14.5 9.7%	10.3 27.1%
Week 252	39.9 13%	12.3 8.3%	16.1 42.4%
Week 264	32.8 10.7%	11.5 7.7%	7.1 18.7%
Week 276	35.5 11.6%	17.0 11.4%	20.0 52.6%
Week 288	35.8 11.7%	19.6 13.2%	8.0 21.1%
Week 300	34.7 11.3%	16.7 11.2%	26.3 69.2%
Week 312	30.6 10%	15.6 10.5%	26.9 70.8%

11. Secondary Outcome

Title	Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) Over Time
Description	The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores 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 (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	305	146	37
Week 6	-2.9 (1.21)	-2.4 (1.28)	-2.5 (1.01)
Week 12	-3.1 (1.14)	-2.5 (1.27)	-2.5 (1.03)
Week 24	-3.2 (1.07)	-2.7 (1.36)	-2.7 (1.22)
Week 36	-3.2 (1.20)	-2.9 (1.11)	-3.0 (1.17)
Week 48	-3.4 (1.20)	-2.9 (1.20)	-2.8 (0.97)
Week 60	-3.5 (1.15)	-2.9 (1.07)	-3.1 (0.98)
Week 72	-3.5 (1.03)	-2.9 (1.24)	-3.1 (0.88)
Week 84	-3.5 (1.06)	-2.9 (1.28)	-3.3 (0.62)
Week 96	-3.4 (1.11)	-3.1 (1.21)	-3.2 (0.98)
Week 108	-3.5 (1.09)	-3.1 (1.24)	-3.1 (0.94)
Week 120	-3.5 (1.08)	-3.1 (1.29)	-3.2 (0.86)
Week 132	-3.5 (1.02)	-3.1 (1.23)	-3.3 (1.02)
Week 144	-3.4 (1.13)	-3.0 (1.18)	-3.4 (1.04)
Week 156	-3.5 (1.13)	-3.1 (1.11)	-3.6 (1.00)
Week 168	-3.6 (1.17)	-3.2 (1.23)	-3.6 (1.08)
Week 180	-3.6 (1.10)	-3.2 (1.24)	-3.5 (1.13)
Week 192	-3.6 (1.15)	-3.2 (1.31)	-3.6 (1.06)
Week 204	-3.6 (1.13)	-3.1 (1.32)	-3.7 (1.13)
Week 216	-3.6 (1.13)	-3.2 (1.15)	-3.5 (1.02)
Week 228	-3.6 (1.12)	-3.3 (1.37)	-3.7 (0.91)
Week 240	-3.7 (1.12)	-3.2 (1.30)	-3.5 (0.91)
Week 252	-3.7 (1.20)	-3.3 (1.18)	-3.3 (1.04)
Week 264	-3.5 (1.25)	-3.1 (1.24)	-3.4 (1.01)
Week 276	-3.7 (1.01)	-3.1 (1.22)	-3.5 (0.90)
Week 288	-3.7 (1.08)	-3.3 (1.44)	-3.2 (0.75)
Week 300	-3.7 (1.00)	-3.0 (1.38)	-3.4 (0.81)
Week 312	-3.5 (1.10)	-3.2 (1.25)	-3.2 (1.04)

12. Secondary Outcome

Title	Change From Baseline in Clinical Disease Activity Index (CDAI) Over Time
Description	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, and Physician's 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. A negative change from Baseline indicates improvement in disease activity.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	297	144	37
Week 6	-30.0 (12.49)	-27.5 (13.54)	-27.2 (11.42)
Week 12	-31.6 (11.82)	-28.4 (13.87)	-27.9 (11.12)
Week 24	-32.6 (11.81)	-30.6 (13.59)	-29.6 (11.45)
Week 36	-32.2 (12.43)	-31.4 (12.67)	-29.6 (11.63)
Week 48	-34.0 (12.84)	-31.8 (13.35)	-29.1 (10.82)
Week 60	-34.7 (12.52)	-32.4 (12.18)	-32.2 (12.09)
Week 72	-34.3 (11.71)	-32.3 (13.33)	-31.8 (10.88)
Week 84	-34.9 (12.08)	-31.0 (13.36)	-33.5 (9.66)
Week 96	-33.4 (11.71)	-32.1 (12.37)	-31.3 (10.86)
Week 108	-34.5 (11.83)	-32.4 (12.79)	-32.3 (10.81)
Week 120	-34.8 (11.87)	-32.3 (12.94)	-34.0 (10.75)
Week 132	-35.0 (12.24)	-32.7 (12.39)	-34.5 (12.14)
Week 144	-35.0 (12.21)	-33.1 (12.67)	-36.2 (12.03)
Week 156	-35.6 (12.24)	-33.6 (12.25)	-36.1 (11.80)
Week 168	-36.2 (13.01)	-33.8 (12.97)	-37.6 (13.08)
Week 180	-35.5 (12.60)	-34.0 (12.13)	-36.9 (12.07)
Week 192	-35.6 (12.25)	-34.0 (12.89)	-38.6 (11.76)
Week 204	-36.0 (12.36)	-33.8 (13.69)	-37.9 (12.59)
Week 216	-35.8 (13.19)	-33.9 (11.87)	-37.3 (11.62)
Week 228	-35.6 (12.68)	-35.5 (13.31)	-37.9 (11.55)
Week 240	-36.4 (12.95)	-34.7 (13.02)	-35.8 (11.07)
Week 252	-35.9 (13.41)	-35.3 (12.58)	-34.3 (11.71)
Week 264	-35.5 (13.66)	-33.2 (12.38)	-33.5 (12.49)
Week 276	-36.5 (12.59)	-33.6 (12.16)	-34.7 (11.92)
Week 288	-36.9 (13.22)	-35.3 (14.34)	-33.5 (10.25)
Week 300	-36.0 (12.17)	-32.9 (11.86)	-34.6 (11.27)
Week 312	-35.9 (12.43)	-34.4 (12.63)	-34.0 (11.62)

13. Secondary Outcome

Title	Change From Baseline in SimplifiedDisease Activity Index (SDAI) Over Time
Description	The simplified disease activity index (SDAI) is a composite index for assessing disease activity based on the summation of the counts of tender joint count (out of 28 evaluated joints) and swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm, Physician's Global Assessment of Disease Activity measured on a VAS from 0 to 10 cm and hsCRP (mg/dL). The total SDAI score ranges from 0 to 86 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	297	144	37
Week 6	-38.8 (25.57)	-37.2 (27.36)	-40.8 (29.76)
Week 12	-40.6 (24.84)	-38.6 (26.09)	-41.7 (30.24)
Week 24	-42.0 (23.35)	-36.7 (43.09)	-38.2 (33.62)
Week 36	-41.8 (25.10)	-41.6 (25.59)	-44.5 (31.98)
Week 48	-42.9 (23.24)	-41.6 (25.26)	-44.6 (29.09)
Week 60	-44.3 (24.21)	-42.5 (24.51)	-41.4 (22.38)
Week 72	-43.4 (24.62)	-41.9 (27.31)	-41.8 (21.19)
Week 84	-42.7 (28.14)	-39.0 (31.94)	-44.7 (20.79)
Week 96	-42.0 (18.50)	-42.4 (27.17)	-43.2 (22.39)
Week 108	-43.6 (27.35)	-42.9 (24.31)	-44.0 (21.38)
Week 120	-42.7 (22.25)	-43.7 (25.88)	-43.4 (23.39)
Week 132	-43.4 (19.92)	-41.4 (27.64)	-44.2 (23.86)
Week 144	-41.7 (22.60)	-43.0 (29.91)	-46.0 (25.20)
Week 156	-42.8 (21.64)	-43.6 (29.88)	-48.0 (23.98)
Week 168	-43.7 (23.75)	-43.2 (28.55)	-46.4 (23.28)
Week 180	-45.6 (26.65)	-45.0 (27.57)	-47.2 (24.08)
Week 192	-44.7 (30.13)	-44.4 (27.94)	-48.5 (25.36)
Week 204	-44.1 (35.23)	-43.5 (28.81)	-47.6 (24.55)
Week 216	-47.3 (27.43)	-44.2 (26.69)	-47.4 (23.26)
Week 228	-46.0 (27.33)	-47.9 (28.86)	-48.6 (21.47)
Week 240	-46.8 (31.40)	-44.2 (29.63)	-45.0 (21.97)
Week 252	-45.9 (25.86)	-45.7 (29.98)	-44.3 (23.50)
Week 264	-44.9 (24.26)	-43.5 (30.06)	-44.4 (21.96)
Week 276	-46.3 (20.01)	-44.2 (26.93)	-47.4 (20.53)
Week 288	-47.1 (22.36)	-48.3 (30.14)	-41.6 (17.15)
Week 300	-47.4 (20.47)	-41.6 (26.38)	-42.7 (19.05)
Week 312	-45.8 (28.64)	-45.8 (28.89)	-41.2 (17.55)

14. Secondary Outcome

Title	Change From Baseline in Tender Joint Count (TJC68) Over Time
Description	Sixty-eight joints were assessed by an evaluator for tenderness or pain. The presence of tenderness was scored as a "1" and absence of tenderness as a "0". The total tender joint count is the sum of the scores, and ranges from 0 to 68 (worst).
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	-20.6 (12.81)	-21.3 (14.53)	-22.1 (12.90)
Week 12	-21.3 (12.47)	-22.5 (14.65)	-20.5 (11.18)
Week 24	-22.0 (12.96)	-23.9 (14.60)	-22.9 (12.17)
Week 36	-21.7 (12.58)	-24.2 (14.45)	-23.4 (13.56)
Week 48	-23.1 (13.61)	-24.1 (14.43)	-24.0 (13.13)
Week 60	-23.6 (13.56)	-25.0 (14.42)	-25.6 (13.54)
Week 72	-23.3 (13.06)	-24.3 (14.48)	-26.1 (13.12)
Week 84	-23.2 (12.71)	-23.4 (14.23)	-27.4 (13.32)
Week 96	-23.1 (12.90)	-23.9 (14.58)	-24.6 (11.94)
Week 108	-23.3 (12.62)	-23.7 (14.22)	-25.2 (12.31)
Week 120	-23.1 (13.13)	-23.9 (14.17)	-26.9 (12.72)
Week 132	-23.1 (12.79)	-23.7 (13.95)	-26.8 (13.74)
Week 144	-23.5 (13.28)	-23.8 (13.50)	-29.3 (13.19)
Week 156	-23.7 (13.21)	-23.9 (13.00)	-28.1 (13.63)
Week 168	-24.1 (13.82)	-24.4 (13.86)	-31.0 (14.12)
Week 180	-23.7 (13.60)	-24.9 (14.12)	-29.5 (12.96)
Week 192	-24.0 (13.75)	-24.4 (14.15)	-31.3 (13.80)
Week 204	-24.2 (13.77)	-23.6 (14.35)	-30.4 (14.53)
Week 216	-24.2 (13.82)	-24.1 (13.87)	-31.6 (13.80)
Week 228	-23.9 (13.57)	-26.6 (14.65)	-30.5 (13.69)
Week 240	-24.7 (14.09)	-25.6 (14.47)	-29.4 (14.28)
Week 252	-24.2 (13.78)	-25.6 (14.14)	-27.5 (13.26)
Week 264	-23.7 (13.56)	-23.7 (13.28)	-27.0 (13.76)
Week 276	-23.6 (13.55)	-23.9 (13.76)	-28.0 (14.41)
Week 288	-24.9 (14.42)	-25.7 (14.87)	-26.6 (14.42)
Week 300	-24.3 (14.04)	-24.5 (15.18)	-28.2 (14.10)
Week 312	-24.1 (13.82)	-23.2 (14.08)	-26.8 (14.48)

15. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count (SJC66) Over Time
Description	Sixty-six joints were assessed by an evaluator for swelling. The presence of swelling was scored as a "1" and absence of swelling as a "0". The total swollen joint count is the sum of the scores, and ranges from 0 to 66 (worst).
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	-12.8 (7.76)	-13.5 (10.89)	-14.5 (8.70)
Week 12	-13.7 (7.95)	-13.9 (11.26)	-13.5 (6.72)
Week 24	-14.2 (8.31)	-14.7 (10.87)	-15.7 (5.67)
Week 36	-14.1 (8.26)	-15.1 (10.39)	-15.6 (5.94)
Week 48	-15.3 (9.47)	-15.4 (11.19)	-16.0 (6.10)
Week 60	-15.6 (9.52)	-15.9 (11.83)	-17.4 (9.36)
Week 72	-15.1 (8.50)	-15.5 (10.47)	-17.0 (6.31)
Week 84	-15.6 (9.18)	-14.7 (9.96)	-17.0 (6.68)
Week 96	-15.3 (9.27)	-14.7 (9.48)	-16.6 (6.79)
Week 108	-15.2 (8.72)	-15.2 (10.17)	-16.6 (6.96)
Week 120	-15.6 (8.77)	-14.8 (9.06)	-17.5 (7.15)
Week 132	-15.7 (9.23)	-14.6 (9.79)	-17.3 (7.11)
Week 144	-15.9 (9.03)	-15.3 (9.81)	-18.6 (7.17)
Week 156	-16.1 (9.74)	-15.5 (9.53)	-17.5 (7.89)
Week 168	-16.9 (11.11)	-15.8 (10.51)	-20.0 (9.94)
Week 180	-16.6 (10.67)	-16.2 (10.61)	-20.0 (9.91)
Week 192	-16.4 (9.87)	-15.8 (9.23)	-20.7 (10.08)
Week 204	-16.7 (10.60)	-15.9 (9.53)	-19.6 (10.22)
Week 216	-16.6 (10.29)	-16.1 (8.86)	-20.4 (10.12)
Week 228	-16.2 (9.51)	-17.3 (10.79)	-19.8 (10.16)
Week 240	-16.8 (10.41)	-17.0 (10.43)	-18.8 (7.86)
Week 252	-16.8 (10.63)	-16.9 (9.37)	-18.1 (7.78)
Week 264	-17.7 (11.38)	-16.1 (8.72)	-18.3 (7.55)
Week 276	-17.8 (11.35)	-17.0 (10.60)	-18.9 (7.74)
Week 288	-17.4 (11.28)	-17.8 (11.76)	-18.7 (7.67)
Week 300	-16.7 (10.21)	-17.1 (10.31)	-19.3 (7.72)
Week 312	-16.7 (9.71)	-17.4 (10.41)	-18.6 (7.51)

16. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessment of Disease Activity Over Time
Description	The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a visual analog scale (VAS) from 0 to 100 mm, where 0 mm indicates no disease activity and 100 mm indicates severe disease activity
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	298	147	38
Week 6	-46.8 (20.58)	-35.5 (21.53)	-38.4 (24.08)
Week 12	-48.9 (20.45)	-39.1 (22.99)	-37.5 (21.78)
Week 24	-51.2 (18.71)	-42.5 (21.24)	-40.9 (22.79)
Week 36	-51.6 (19.08)	-42.7 (20.96)	-39.5 (24.20)
Week 48	-52.8 (19.12)	-45.6 (19.29)	-40.6 (20.97)
Week 60	-54.2 (16.44)	-47.1 (19.64)	-44.7 (24.33)
Week 72	-53.4 (17.46)	-45.9 (18.58)	-47.2 (18.47)
Week 84	-54.3 (16.44)	-43.4 (21.41)	-48.5 (17.25)
Week 96	-52.3 (17.69)	-45.7 (20.42)	-46.8 (20.97)
Week 108	-55.5 (16.72)	-45.9 (18.75)	-47.4 (21.09)
Week 120	-55.9 (16.38)	-48.6 (18.23)	-50.1 (21.51)
Week 132	-56.1 (16.60)	-50.1 (17.19)	-52.5 (20.62)
Week 144	-56.7 (15.79)	-48.2 (18.28)	-51.4 (19.66)
Week 156	-57.0 (16.90)	-48.9 (18.89)	-52.4 (19.49)
Week 168	-57.0 (15.94)	-51.9 (20.24)	-55.6 (21.25)
Week 180	-57.2 (17.11)	-53.0 (18.04)	-53.1 (19.34)
Week 192	-56.3 (17.25)	-52.1 (16.56)	-55.1 (20.69)
Week 204	-58.0 (16.73)	-52.9 (18.09)	-54.7 (19.50)
Week 216	-58.3 (16.50)	-50.8 (18.27)	-51.3 (20.42)
Week 228	-56.3 (19.63)	-53.2 (17.28)	-55.0 (19.69)
Week 240	-58.1 (17.63)	-52.8 (16.04)	-49.6 (18.67)
Week 252	-57.2 (17.56)	-53.9 (17.10)	-52.2 (18.12)
Week 264	-56.5 (16.68)	-50.4 (18.09)	-46.4 (18.60)
Week 276	-56.9 (16.79)	-53.5 (17.07)	-50.1 (17.96)
Week 288	-57.3 (18.97)	-56.3 (17.25)	-49.4 (16.31)
Week 300	-56.8 (17.93)	-52.9 (17.33)	-53.6 (17.36)
Week 312	-58.7 (16.12)	-55.2 (17.19)	-49.4 (17.96)

17. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Disease Activity Over Time
Description	The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	305	146	37
Week 6	-35.4 (29.83)	-27.2 (27.74)	-26.1 (27.46)
Week 12	-37.5 (29.00)	-29.2 (28.05)	-31.3 (23.13)
Week 24	-36.9 (28.97)	-30.4 (31.16)	-32.9 (25.63)
Week 36	-37.1 (30.36)	-32.6 (28.62)	-34.9 (26.00)
Week 48	-39.2 (30.36)	-30.7 (30.46)	-23.6 (26.58)
Week 60	-40.8 (28.95)	-34.4 (28.36)	-38.3 (24.46)
Week 72	-40.3 (27.36)	-32.1 (30.19)	-26.3 (30.70)
Week 84	-40.1 (30.37)	-32.0 (31.27)	-39.4 (21.35)
Week 96	-38.1 (30.34)	-33.5 (33.51)	-33.5 (22.08)
Week 108	-40.8 (29.75)	-35.0 (29.93)	-32.1 (20.65)
Week 120	-40.6 (29.76)	-32.4 (32.91)	-36.6 (28.02)
Week 132	-40.1 (29.99)	-37.0 (28.43)	-38.4 (27.02)
Week 144	-37.7 (30.73)	-36.8 (28.24)	-33.9 (29.68)
Week 156	-39.7 (32.65)	-36.9 (25.93)	-38.6 (21.61)
Week 168	-42.7 (29.04)	-37.9 (29.10)	-39.0 (32.84)
Week 180	-40.3 (29.52)	-30.7 (33.34)	-33.3 (34.03)
Week 192	-41.0 (28.73)	-33.4 (33.30)	-42.1 (23.97)
Week 204	-42.0 (29.28)	-33.2 (34.00)	-43.7 (25.60)
Week 216	-39.0 (32.18)	-32.5 (30.72)	-35.6 (27.03)
Week 228	-38.4 (32.29)	-28.5 (37.86)	-40.1 (24.11)
Week 240	-41.9 (30.43)	-37.6 (28.56)	-33.3 (29.03)
Week 252	-40.6 (32.12)	-33.8 (31.76)	-33.5 (35.96)
Week 264	-38.5 (31.53)	-31.6 (34.26)	-32.7 (34.87)
Week 276	-42.4 (27.53)	-36.8 (29.40)	-26.0 (33.79)
Week 288	-43.3 (27.99)	-38.5 (32.21)	-32.2 (28.16)
Week 300	-38.8 (29.04)	-33.4 (34.89)	-31.6 (25.93)
Week 312	-36.5 (32.10)	-39.4 (30.60)	-37.7 (29.67)

18. Secondary Outcome

Title	Change From Baseline in Patient's Assessment of Pain Over Time
Description	Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	305	146	37
Week 6	-38.5 (27.16)	-29.9 (24.46)	-30.0 (26.37)
Week 12	-41.3 (26.07)	-29.9 (26.20)	-31.9 (20.23)
Week 24	-42.2 (25.41)	-30.9 (28.77)	-36.0 (21.73)
Week 36	-40.6 (26.41)	-34.6 (26.56)	-34.8 (21.83)
Week 48	-42.4 (26.50)	-31.9 (28.73)	-32.6 (23.67)
Week 60	-41.9 (27.89)	-32.2 (26.50)	-38.6 (23.34)
Week 72	-42.5 (24.76)	-32.0 (25.38)	-31.4 (22.95)
Week 84	-42.1 (25.87)	-33.3 (26.52)	-43.0 (20.51)
Week 96	-40.5 (28.02)	-34.2 (26.14)	-37.6 (20.15)
Week 108	-43.6 (26.28)	-33.9 (27.60)	-36.3 (23.12)
Week 120	-43.0 (26.67)	-36.2 (27.69)	-41.9 (21.40)
Week 132	-42.2 (26.89)	-36.7 (26.71)	-34.4 (27.27)
Week 144	-41.7 (27.02)	-36.7 (27.14)	-33.8 (24.60)
Week 156	-43.5 (25.72)	-37.4 (25.27)	-34.6 (24.91)
Week 168	-43.6 (27.19)	-38.8 (27.67)	-41.6 (25.76)
Week 180	-42.7 (26.54)	-33.6 (30.24)	-36.5 (29.20)
Week 192	-41.6 (27.90)	-33.8 (29.13)	-39.9 (25.44)
Week 204	-44.4 (25.26)	-33.4 (33.05)	-41.9 (22.39)
Week 216	-42.2 (28.01)	-32.5 (32.06)	-33.6 (25.98)
Week 228	-45.1 (24.96)	-29.6 (35.17)	-39.8 (24.70)
Week 240	-43.4 (27.78)	-34.1 (31.98)	-36.1 (25.38)
Week 252	-44.4 (27.49)	-34.3 (28.12)	-38.3 (24.92)
Week 264	-44.0 (25.43)	-35.6 (31.33)	-38.2 (24.11)
Week 276	-46.3 (24.53)	-35.6 (27.39)	-34.1 (26.80)
Week 288	-46.2 (25.61)	-37.6 (28.74)	-33.3 (23.30)
Week 300	-43.0 (25.18)	-34.7 (32.36)	-29.9 (30.21)
Week 312	-44.1 (25.87)	-40.3 (27.37)	-33.4 (30.11)

19. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) Over Time
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.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	304	146	37
Week 6	-0.7 (0.62)	-0.6 (0.56)	-0.6 (0.47)
Week 12	-0.7 (0.64)	-0.6 (0.63)	-0.7 (0.55)
Week 24	-0.8 (0.60)	-0.6 (0.61)	-0.7 (0.58)
Week 36	-0.7 (0.66)	-0.6 (0.62)	-0.7 (0.66)
Week 48	-0.8 (0.63)	-0.7 (0.61)	-0.7 (0.58)
Week 60	-0.8 (0.67)	-0.7 (0.66)	-0.7 (0.52)
Week 72	-0.8 (0.65)	-0.7 (0.63)	-0.7 (0.54)
Week 84	-0.9 (0.62)	-0.7 (0.64)	-0.7 (0.57)
Week 96	-0.8 (0.64)	-0.8 (0.69)	-0.8 (0.52)
Week 108	-0.9 (0.67)	-0.7 (0.67)	-0.7 (0.58)
Week 120	-0.8 (0.64)	-0.7 (0.64)	-0.8 (0.62)
Week 132	-0.9 (0.66)	-0.7 (0.64)	-0.8 (0.51)
Week 144	-0.8 (0.72)	-0.8 (0.68)	-0.7 (0.61)
Week 156	-0.8 (0.69)	-0.7 (0.57)	-0.8 (0.61)
Week 168	-0.8 (0.68)	-0.7 (0.67)	-0.8 (0.60)
Week 180	-0.8 (0.70)	-0.7 (0.70)	-0.7 (0.64)
Week 192	-0.8 (0.68)	-0.7 (0.69)	-0.8 (0.57)
Week 204	-0.9 (0.68)	-0.7 (0.79)	-0.8 (0.51)
Week 216	-0.8 (0.69)	-0.7 (0.73)	-0.8 (0.61)
Week 228	-0.9 (0.72)	-0.7 (0.77)	-0.7 (0.61)
Week 240	-0.8 (0.69)	-0.7 (0.77)	-0.6 (0.61)
Week 252	-0.9 (0.69)	-0.7 (0.77)	-0.7 (0.59)
Week 264	-0.8 (0.68)	-0.7 (0.65)	-0.7 (0.59)
Week 276	-0.8 (0.69)	-0.6 (0.66)	-0.7 (0.61)
Week 288	-0.9 (0.70)	-0.7 (0.74)	-0.8 (0.61)
Week 300	-0.8 (0.76)	-0.7 (0.70)	-0.7 (0.68)
Week 312	-0.8 (0.71)	-0.8 (0.74)	-0.7 (0.69)

20. Secondary Outcome

Title	Change From Baseline in High-sensitivity C-reactive Protein (hsCRP) Over Time
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	306	149	38
Week 6	-7.9 (21.74)	-10.0 (21.95)	-13.0 (29.00)
Week 12	-9.0 (18.96)	-10.7 (20.94)	-12.8 (26.93)
Week 24	-9.4 (17.38)	-7.2 (36.97)	-9.1 (29.38)
Week 36	-9.5 (18.62)	-11.1 (22.03)	-13.5 (28.34)
Week 48	-8.8 (17.50)	-10.2 (22.28)	-13.3 (22.69)
Week 60	-9.6 (17.78)	-10.3 (22.10)	-11.0 (21.62)
Week 72	-9.2 (19.42)	-9.9 (22.95)	-11.2 (20.16)
Week 84	-8.3 (24.66)	-10.0 (28.56)	-10.2 (16.57)
Week 96	-10.1 (17.74)	-10.3 (22.36)	-11.1 (17.61)
Week 108	-9.8 (21.56)	-10.7 (19.36)	-10.8 (17.39)
Week 120	-8.4 (18.27)	-10.9 (19.63)	-9.2 (18.62)
Week 132	-8.9 (15.19)	-9.0 (21.32)	-9.3 (17.53)
Week 144	-7.3 (17.15)	-9.9 (23.45)	-5.9 (26.82)
Week 156	-8.6 (16.60)	-6.0 (52.17)	-10.9 (18.20)
Week 168	-7.7 (18.37)	-7.5 (28.96)	-8.8 (17.88)
Week 180	-10.0 (19.41)	-10.3 (21.44)	-9.2 (19.16)
Week 192	-9.4 (23.81)	-9.9 (21.04)	-9.3 (20.07)
Week 204	-8.4 (28.90)	-9.6 (21.29)	-9.0 (19.07)
Week 216	-11.5 (20.22)	-10.0 (22.42)	-8.4 (19.70)
Week 228	-11.0 (20.71)	-12.2 (20.89)	-10.0 (17.46)
Week 240	-10.6 (24.45)	-9.1 (22.38)	-9.2 (17.55)
Week 252	-10.4 (19.33)	-9.4 (24.28)	-9.9 (18.83)
Week 264	-11.2 (21.02)	-9.9 (23.99)	-11.1 (18.19)
Week 276	-10.5 (18.04)	-11.2 (20.20)	-10.9 (17.95)
Week 288	-10.6 (16.09)	-12.9 (21.85)	-7.5 (14.48)
Week 300	-11.1 (14.63)	-11.4 (21.67)	-11.0 (19.69)
Week 312	-10.3 (22.22)	-12.0 (21.14)	-8.7 (15.19)

21. Secondary Outcome

Title	Change From Baseline in in Functional Assessment of Chronic Illness Therapy (FACIT) - Fatigue Scale Over Time
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 (4 = not at all fatigued to 0 = very much fatigued). The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better quality of life. A positive change from Baseline indicates improvement.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	304	146	37
Week 6	9.5 (10.50)	9.0 (9.69)	8.8 (9.26)
Week 12	9.9 (10.49)	8.7 (10.87)	8.6 (10.43)
Week 24	10.7 (10.04)	10.6 (11.60)	8.3 (9.65)
Week 36	10.1 (10.59)	10.0 (11.58)	8.0 (11.50)
Week 48	10.4 (10.58)	10.8 (10.44)	8.4 (10.83)
Week 72	10.8 (9.55)	10.9 (10.64)	9.2 (11.44)
Week 96	10.3 (10.45)	11.7 (12.72)	9.5 (11.27)
Week 108	10.5 (10.49)	11.9 (12.08)	7.9 (10.62)
Week 120	11.0 (10.76)	11.6 (11.95)	10.7 (11.30)
Week 132	11.4 (10.13)	10.7 (11.47)	10.7 (10.36)
Week 144	9.9 (11.36)	11.2 (12.09)	9.8 (11.67)
Week 156	10.6 (10.94)	11.2 (11.48)	8.6 (12.32)
Week 168	10.8 (12.27)	10.6 (12.46)	11.4 (13.18)
Week 180	11.0 (11.59)	9.6 (13.56)	11.4 (12.45)
Week 192	10.8 (10.50)	10.9 (11.82)	11.5 (13.27)
Week 204	11.3 (10.56)	10.2 (13.01)	11.2 (12.70)
Week 216	11.4 (11.93)	10.4 (13.92)	10.1 (12.87)
Week 228	11.0 (11.25)	10.8 (14.00)	11.1 (13.18)
Week 240	11.9 (10.93)	11.4 (13.08)	9.2 (13.81)
Week 252	11.5 (10.83)	10.2 (13.68)	8.4 (13.48)
Week 264	11.6 (10.95)	10.7 (12.52)	7.8 (13.94)
Week 276	12.1 (10.98)	9.2 (13.02)	7.3 (13.02)
Week 288	11.6 (10.88)	12.3 (11.83)	9.0 (13.94)
Week 300	11.1 (11.14)	9.7 (13.12)	7.0 (13.46)
Week 312	10.7 (11.24)	11.6 (12.67)	8.6 (14.35)

22. Secondary Outcome

Title	Change From Baseline in Work Instability Scale for RA (RA-WIS) Over Time
Description	RA-WIS is a tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score < 10 means low risk, scores between 10 and 17 indicate medium risk, and scores > 17 indicate high risk of work instability. A negative change from Baseline indicates improvement in work instability.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population who were currently working at Baseline and at each visit visit and with available data at each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	87	53	13
Week 6	-6.2 (5.55)	-3.3 (5.51)	-4.1 (3.00)
Week 12	-6.6 (6.16)	-4.0 (6.32)	-4.2 (3.35)
Week 24	-7.0 (6.51)	-4.6 (6.63)	-3.6 (3.53)
Week 36	-6.8 (6.29)	-4.6 (6.21)	-3.3 (6.18)
Week 48	-6.8 (5.94)	-5.0 (6.47)	-3.5 (4.98)
Week 72	-7.5 (6.83)	-4.8 (6.27)	-4.3 (4.10)
Week 96	-6.5 (6.72)	-6.3 (7.55)	-4.0 (4.18)
Week 108	-6.8 (6.80)	-6.5 (6.71)	-3.5 (4.80)
Week 120	-7.6 (6.66)	-5.1 (7.38)	-5.7 (4.44)
Week 132	-7.2 (6.04)	-5.6 (6.99)	-4.7 (3.47)
Week 144	-5.9 (6.51)	-5.6 (7.65)	-4.3 (3.41)
Week 156	-6.2 (7.13)	-4.3 (7.62)	-4.9 (3.72)
Week 168	-5.8 (6.01)	-4.3 (6.96)	-5.1 (6.69)
Week 180	-5.3 (6.61)	-3.5 (7.03)	-4.2 (3.19)
Week 192	-5.5 (6.42)	-3.5 (7.36)	-4.3 (2.93)
Week 204	-6.4 (7.06)	-3.7 (7.52)	-5.0 (3.78)
Week 216	-6.0 (7.55)	-3.4 (7.11)	-5.0 (2.92)
Week 228	-6.5 (7.16)	-1.9 (7.55)	-4.6 (4.24)
Week 240	-5.9 (7.05)	-3.1 (7.61)	-4.5 (4.09)
Week 252	-5.8 (6.43)	-2.0 (8.05)	-5.0 (3.70)
Week 264	-5.0 (6.53)	-3.4 (8.00)	-4.5 (3.89)
Week 276	-5.0 (6.74)	-2.7 (8.27)	-5.0 (2.52)
Week 288	-5.0 (7.05)	-4.8 (7.38)	-4.8 (3.45)
Week 300	-4.6 (7.23)	-4.3 (8.51)	-4.6 (4.07)
Week 312	-4.2 (7.00)	-3.9 (8.37)	-2.9 (4.45)

23. Secondary Outcome

Title	Change From Baseline in EuroQoL-5D (EQ-5D) Index Over Time
Description	The EQ-5D-5L is a generic measure of health status consisting of two parts. The first part (the descriptive system) assesses health in five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which is rated on 5 levels of severity (1: no problem, 2: slight problems, 3: moderate problems, 4: severe problems, 5: extreme problems). A health state index score was calculated from individual health profiles using a UK scoring algorithm. Health state index scores generally range from less than 0 (where 0 is the value of a health state equivalent to dead; negative values representing values as worse than dead) to 1 (the value of full health), with higher scores indicating higher health utility. The higher the score the better the health status. A positive change from baseline indicates improvement in health status.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	304	146	37
Week 6	0.2 (0.24)	0.2 (0.27)	0.2 (0.18)
Week 12	0.2 (0.23)	0.2 (0.29)	0.2 (0.14)
Week 24	0.2 (0.23)	0.2 (0.28)	0.2 (0.16)
Week 36	0.2 (0.24)	0.2 (0.27)	0.2 (0.16)
Week 48	0.2 (0.25)	0.2 (0.31)	0.1 (0.20)
Week 72	0.2 (0.24)	0.2 (0.28)	0.2 (0.16)
Week 96	0.2 (0.25)	0.2 (0.28)	0.2 (0.15)
Week 108	0.2 (0.26)	0.2 (0.28)	0.1 (0.16)
Week 120	0.2 (0.26)	0.2 (0.27)	0.2 (0.16)
Week 132	0.2 (0.25)	0.2 (0.26)	0.2 (0.15)
Week 144	0.2 (0.28)	0.2 (0.27)	0.2 (0.17)
Week 156	0.2 (0.27)	0.2 (0.26)	0.1 (0.18)
Week 168	0.2 (0.29)	0.2 (0.28)	0.2 (0.20)
Week 180	0.2 (0.27)	0.2 (0.33)	0.2 (0.20)
Week 192	0.2 (0.27)	0.2 (0.27)	0.2 (0.20)
Week 204	0.2 (0.27)	0.2 (0.31)	0.2 (0.21)
Week 216	0.2 (0.29)	0.2 (0.30)	0.2 (0.18)
Week 228	0.2 (0.26)	0.2 (0.31)	0.1 (0.22)
Week 240	0.3 (0.29)	0.2 (0.26)	0.1 (0.22)
Week 252	0.2 (0.26)	0.2 (0.28)	0.2 (0.22)
Week 264	0.3 (0.29)	0.2 (0.25)	0.1 (0.23)
Week 276	0.2 (0.30)	0.2 (0.26)	0.1 (0.22)
Week 288	0.3 (0.27)	0.2 (0.27)	0.1 (0.23)
Week 300	0.2 (0.28)	0.2 (0.27)	0.1 (0.19)
Week 312	0.2 (0.29)	0.2 (0.26)	0.1 (0.25)

24. Secondary Outcome

Title	Change From Baseline in EuroQoL-5D VAS Score Over Time
Description	The EQ-5D-5L is a generic measure of health status consisting of two parts. The second part of the questionnaire consists of a visual analog scale (VAS) on which the participant rates his/her perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). A positive change from baseline indicates improvement.
Time Frame	Baseline (of the preceding RCT study) and Weeks 6, 12, 24, 36, 48, 72, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, 216, 228, 240, 252, 264, 276, 288, 300, and 312

Outcome Measure Data

Analysis Population Description

Open-label treated population with available data at Baseline and each time point

Arm/Group Title	Upadacitinib Never Titrated	Upadacitinib Titrated Up and Not Down	Upadacitinib Titrated Up and Down
Arm/Group Description	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg twice a day (BID). From January 2017 participants were transitioned to once-daily (QD) dose of 15 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib.	Participants received treatment with upadacitinib for up to 312 weeks. The starting dose was 6 mg BID. Participants who did not achieve protocol-specified improvement criteria at Week 6 or at any visits thereafter were up-titrated to upadacitinib 12 mg BID. From January 2017 participants were transitioned to once-daily dose of 30 mg upadacitinib. The upadacitinib dose was decreased back to 6 mg BID (or 15 mg QD from January 2017) per Investigator's judgment or safety and/or tolerability concerns.
Measure Participants	304	146	37
Week 6	23.7 (25.21)	14.4 (24.94)	21.6 (20.49)
Week 12	26.0 (25.62)	15.9 (25.83)	19.4 (25.07)
Week 24	27.5 (25.24)	16.8 (27.31)	20.7 (20.67)
Week 36	27.0 (26.29)	18.6 (27.10)	18.6 (21.05)
Week 48	25.9 (26.87)	19.1 (28.61)	19.7 (21.07)
Week 72	28.0 (24.36)	21.9 (26.33)	26.7 (21.43)
Week 96	27.5 (26.86)	22.4 (27.73)	25.4 (19.25)
Week 108	28.8 (25.72)	23.2 (25.81)	20.5 (19.06)
Week 120	28.4 (27.22)	23.7 (25.36)	27.2 (23.54)
Week 132	26.3 (28.75)	23.5 (26.23)	28.1 (19.62)
Week 144	28.6 (26.71)	23.5 (24.29)	24.7 (25.32)
Week 156	29.9 (25.48)	22.5 (24.62)	22.1 (23.52)
Week 168	30.3 (25.29)	22.6 (23.74)	28.1 (24.06)
Week 180	30.0 (24.30)	22.0 (27.24)	27.0 (21.68)
Week 192	29.7 (24.65)	23.6 (26.41)	30.8 (21.96)
Week 204	32.0 (24.41)	23.1 (27.13)	30.7 (22.99)
Week 216	30.0 (26.93)	24.0 (26.40)	28.0 (21.73)
Week 228	31.6 (24.92)	19.7 (26.70)	29.5 (23.85)
Week 240	31.3 (26.18)	21.9 (25.62)	28.4 (26.55)
Week 252	31.2 (24.46)	22.8 (26.74)	25.6 (23.74)
Week 264	30.8 (25.30)	22.2 (23.60)	21.9 (24.81)
Week 276	32.4 (23.37)	20.5 (25.68)	25.4 (20.62)
Week 288	32.3 (24.66)	24.6 (25.54)	25.3 (22.57)
Week 300	30.5 (24.39)	20.4 (27.31)	23.6 (17.27)
Week 312	31.2 (25.15)	25.8 (24.81)	24.1 (25.18)

25. Secondary Outcome

Title	Percentage of Participants With Satisfactory Humoral Response to PCV-13 12 Weeks After Vaccination
Description	Satisfactory humoral response is defined as greater than or equal to 2-fold increase in antibody concentration from the vaccination Baseline in at least 6 out of the 12 pneumococcal antigens 1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F).
Time Frame	Vaccination Baseline and 12 weeks after vaccination

Outcome Measure Data

Analysis Population Description

The sub-study full analysis set (FAS) included all participants enrolled in the sub-study who received PCV-13 vaccination and at least 1 dose of upadacitinib 15 mg or 30 mg after vaccination during the sub-study. Analysis includes participants with available data at the Week 12 visit of the sub-study.

Arm/Group Title	Upadacitinib 15 mg + PCV-13	Upadacitinib 30 mg + PCV-13
Arm/Group Description	Participants receiving 15 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).	Participants receiving 30 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).
Measure Participants	79	22
Number (95% Confidence Interval) [percentage of participants]	64.6 21.1%	54.5 36.6%

26. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of Anti-pneumococcal Antibody Levels to Each of the 12 Pneumococcal Antigens 4 and 12 Weeks After Vaccination
Time Frame	Vaccination Baseline and 4 and 12 weeks after vaccination

Outcome Measure Data

Analysis Population Description

Sub-study full analysis set with available data at each time point.

Arm/Group Title	Upadacitinib 15 mg + PCV-13	Upadacitinib 30 mg + PCV-13
Arm/Group Description	Participants receiving 15 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).	Participants receiving 30 mg upadacitinib QD were administered a single-dose of pneumococcal 13-valent conjugate vaccine (PCV-13).
Measure Participants	83	23
Antigen 1: Week 4	7.90	6.53
Antigen 1: Week 12	8.07	6.54
Antigen 3: Week 4	2.59	2.30
Antigen 3: Week 12	2.26	2.24
Antigen 4: Week 4	5.61	3.82
Antigen 4: Week 12	5.17	3.39
Antigen 5: Week 4	1.90	1.60
Antigen 5: Week 12	1.84	1.57
Antigen 6B: Week 4	4.50	3.10
Antigen 6B: Week 12	3.90	3.25
Antigen 7F: Week 4	3.58	2.83
Antigen 7F: Week 12	3.30	3.02
Antigen 9V: Week 4	5.69	2.76
Antigen 9V: Week 12	6.18	2.91
Antigen 14: Week 4	2.97	2.42
Antigen 14: Week 12	2.84	2.41
Antigen 18C: Week 4	4.52	3.23
Antigen 18C: Week 12	4.42	3.53
Antigen 19A: Week 4	1.47	1.12
Antigen 19A: Week 12	1.44	1.15
Antigen 19F: Week 4	2.27	2.32
Antigen 19F: Week 12	2.17	1.99
Antigen 23F: Week 4	4.32	3.11
Antigen 23F: Week 12	4.06	3.29

Adverse Events

Time Frame	From the first dose of open-label upadacitinib up to 30 days after the last dose, up to 316 weeks.
Arm/Group Title	Upadacitinib 6 mg BID/15 mg QD		Upadacitinib 12 mg BID/30 mg QD		Upadacitinib 6 mg BID/15 mg QD Post Down-titration
Arm/Group Description	Participants received upadacitinib 6 mg BID. From January 2017 participants were transitioned to 15 mg upadacitinib QD. Includes events that occurred until the time of up-titration for participants who were up-titrated.		Participants received upadacitinib 12 mg BID. From January 2017 participants were transitioned to 30 mg upadacitinib QD. Includes events that occurred from the time of up-titration until time of down titration to 6 mg BID/15 mg QD for participants who titrated up and back down.		Participants who down-titrated to 6 mg BID/15 mg QD after up-titration to 15 mg BID/30 mg QD. Includes events that occurred after down titration.
All Cause Mortality
	Upadacitinib 6 mg BID/15 mg QD		Upadacitinib 12 mg BID/30 mg QD		Upadacitinib 6 mg BID/15 mg QD Post Down-titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/493 (1%)		3/187 (1.6%)		0/38 (0%)
Serious Adverse Events
	Upadacitinib 6 mg BID/15 mg QD		Upadacitinib 12 mg BID/30 mg QD		Upadacitinib 6 mg BID/15 mg QD Post Down-titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	68/493 (13.8%)		42/187 (22.5%)		5/38 (13.2%)
Blood and lymphatic system disorders
BLOOD LOSS ANAEMIA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	4/493 (0.8%)	4	0/187 (0%)	0	0/38 (0%)	0
ANGINA PECTORIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
ANGINA UNSTABLE	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
AORTIC VALVE INCOMPETENCE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
ATRIAL FLUTTER	1/493 (0.2%)	2	0/187 (0%)	0	0/38 (0%)	0
ATRIOVENTRICULAR BLOCK SECOND DEGREE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
CARDIAC FAILURE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
CARDIOMYOPATHY	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
CORONARY ARTERY DISEASE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
CORONARY ARTERY DISSECTION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
MYOCARDIAL INFARCTION	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
MYOCARDIAL ISCHAEMIA	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
STRESS CARDIOMYOPATHY	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Ear and labyrinth disorders
VESTIBULAR DISORDER	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Endocrine disorders
GOITRE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Eye disorders
CORNEAL PERFORATION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
GLAUCOMA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
MACULAR HOLE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Gastrointestinal disorders
ENTEROCOLITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
VOMITING	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
General disorders
CHEST PAIN	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
DEATH	2/493 (0.4%)	2	0/187 (0%)	0	0/38 (0%)	0
Hepatobiliary disorders
HEPATITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
HEPATOTOXICITY	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Infections and infestations
APPENDICITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
BRONCHITIS	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
CELLULITIS	1/493 (0.2%)	1	3/187 (1.6%)	3	0/38 (0%)	0
COVID-19	0/493 (0%)	0	2/187 (1.1%)	2	0/38 (0%)	0
COVID-19 PNEUMONIA	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
DIVERTICULITIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
ENDOMETRITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
GASTROENTERITIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
GASTROENTERITIS VIRAL	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
HEPATITIS A	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
HERPES ZOSTER	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
HISTOPLASMOSIS DISSEMINATED	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
INFLUENZA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
LATENT TUBERCULOSIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PNEUMONIA	7/493 (1.4%)	7	3/187 (1.6%)	3	0/38 (0%)	0
POSTOPERATIVE WOUND INFECTION	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
PYELONEPHRITIS ACUTE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
RESPIRATORY TRACT INFECTION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
SEPSIS	0/493 (0%)	0	2/187 (1.1%)	2	0/38 (0%)	0
SOFT TISSUE INFECTION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
TUBERCULOSIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
VARICELLA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
VARICELLA ZOSTER VIRUS INFECTION	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Injury, poisoning and procedural complications
CONTUSION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
FACIAL BONES FRACTURE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
FALL	1/493 (0.2%)	1	2/187 (1.1%)	2	0/38 (0%)	0
FEMORAL NECK FRACTURE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
FEMUR FRACTURE	1/493 (0.2%)	2	0/187 (0%)	0	0/38 (0%)	0
FOREARM FRACTURE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
HAND FRACTURE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
HIP FRACTURE	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
HUMERUS FRACTURE	2/493 (0.4%)	2	0/187 (0%)	0	0/38 (0%)	0
INCARCERATED INCISIONAL HERNIA	1/493 (0.2%)	2	0/187 (0%)	0	0/38 (0%)	0
INCISIONAL HERNIA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
LOWER LIMB FRACTURE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
MULTIPLE FRACTURES	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
MULTIPLE INJURIES	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
OVERDOSE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
POST PROCEDURAL DISCHARGE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
RADIUS FRACTURE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SKIN LACERATION	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SKULL FRACTURED BASE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
TENDON RUPTURE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
VASCULAR PSEUDOANEURYSM	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Metabolism and nutrition disorders
HYPONATRAEMIA	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	2
Musculoskeletal and connective tissue disorders
ARTHRALGIA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
INTERVERTEBRAL DISC COMPRESSION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
INTERVERTEBRAL DISC PROTRUSION	2/493 (0.4%)	2	0/187 (0%)	0	0/38 (0%)	0
LUMBAR SPINAL STENOSIS	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
OSTEOARTHRITIS	4/493 (0.8%)	4	3/187 (1.6%)	3	0/38 (0%)	0
RHEUMATOID ARTHRITIS	1/493 (0.2%)	1	0/187 (0%)	0	1/38 (2.6%)	1
SPINAL OSTEOARTHRITIS	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
SPONDYLOLISTHESIS	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
SYNOVITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BASAL CELL CARCINOMA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
CLEAR CELL RENAL CELL CARCINOMA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
ENDOMETRIAL CANCER	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
HODGKIN'S DISEASE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
INVASIVE BREAST CARCINOMA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
INVASIVE DUCTAL BREAST CARCINOMA	0/493 (0%)	0	0/187 (0%)	0	1/38 (2.6%)	1
INVASIVE LOBULAR BREAST CARCINOMA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
INVASIVE PAPILLARY BREAST CARCINOMA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
LUNG ADENOCARCINOMA	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
LUNG ADENOCARCINOMA STAGE I	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
NON-SMALL CELL LUNG CANCER	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
PAPILLARY THYROID CANCER	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PROSTATE CANCER	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SEBACEOUS CARCINOMA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SQUAMOUS CELL CARCINOMA OF LUNG	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
SQUAMOUS CELL CARCINOMA OF THE CERVIX	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
THYROID B-CELL LYMPHOMA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Nervous system disorders
BRAIN STEM INFARCTION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
CEREBRAL INFARCTION	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
CEREBROVASCULAR ACCIDENT	0/493 (0%)	0	1/187 (0.5%)	2	0/38 (0%)	0
DIZZINESS	2/493 (0.4%)	2	0/187 (0%)	0	0/38 (0%)	0
HEADACHE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
INTRACRANIAL ANEURYSM	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
LACUNAR INFARCTION	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
METABOLIC ENCEPHALOPATHY	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
OCCIPITAL NEURALGIA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SCIATICA	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SYNCOPE	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Product Issues
DEVICE LOOSENING	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Psychiatric disorders
ANXIETY	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
DEPRESSION	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
DISSOCIATIVE DISORDER	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Renal and urinary disorders
BLADDER PROLAPSE	1/493 (0.2%)	1	1/187 (0.5%)	1	0/38 (0%)	0
Reproductive system and breast disorders
CERVICAL DYSPLASIA	2/493 (0.4%)	2	0/187 (0%)	0	0/38 (0%)	0
HYDROSALPINX	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Respiratory, thoracic and mediastinal disorders
EPISTAXIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
LUNG INFILTRATION	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PARANASAL CYST	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PLEURAL EFFUSION	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PLEURISY	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PNEUMONITIS	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
PULMONARY EMBOLISM	2/493 (0.4%)	2	2/187 (1.1%)	4	0/38 (0%)	0
RESPIRATORY FAILURE	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
SLEEP APNOEA SYNDROME	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Skin and subcutaneous tissue disorders
SKIN ULCER	1/493 (0.2%)	2	0/187 (0%)	0	0/38 (0%)	0
Surgical and medical procedures
ABORTION INDUCED	0/493 (0%)	0	1/187 (0.5%)	1	0/38 (0%)	0
Vascular disorders
DEEP VEIN THROMBOSIS	3/493 (0.6%)	3	2/187 (1.1%)	2	0/38 (0%)	0
PERIPHERAL ARTERY STENOSIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
PERIPHERAL ARTERY THROMBOSIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
VENOUS THROMBOSIS	1/493 (0.2%)	1	0/187 (0%)	0	0/38 (0%)	0
Other (Not Including Serious) Adverse Events
	Upadacitinib 6 mg BID/15 mg QD		Upadacitinib 12 mg BID/30 mg QD		Upadacitinib 6 mg BID/15 mg QD Post Down-titration
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	233/493 (47.3%)		113/187 (60.4%)		23/38 (60.5%)
Blood and lymphatic system disorders
ANAEMIA	7/493 (1.4%)	7	11/187 (5.9%)	12	1/38 (2.6%)	1
LYMPHOPENIA	15/493 (3%)	17	5/187 (2.7%)	6	2/38 (5.3%)	2
NEUTROPENIA	10/493 (2%)	13	2/187 (1.1%)	3	2/38 (5.3%)	2
Gastrointestinal disorders
DIARRHOEA	7/493 (1.4%)	7	10/187 (5.3%)	11	0/38 (0%)	0
General disorders
INFLUENZA LIKE ILLNESS	6/493 (1.2%)	9	10/187 (5.3%)	11	2/38 (5.3%)	2
Infections and infestations
BRONCHITIS	42/493 (8.5%)	66	14/187 (7.5%)	23	6/38 (15.8%)	8
HERPES ZOSTER	22/493 (4.5%)	23	21/187 (11.2%)	24	3/38 (7.9%)	3
LATENT TUBERCULOSIS	10/493 (2%)	10	2/187 (1.1%)	2	2/38 (5.3%)	2
LOWER RESPIRATORY TRACT INFECTION	1/493 (0.2%)	1	1/187 (0.5%)	1	3/38 (7.9%)	4
NASOPHARYNGITIS	47/493 (9.5%)	75	16/187 (8.6%)	19	3/38 (7.9%)	3
PHARYNGITIS	10/493 (2%)	12	3/187 (1.6%)	3	2/38 (5.3%)	2
SINUSITIS	13/493 (2.6%)	15	14/187 (7.5%)	24	0/38 (0%)	0
UPPER RESPIRATORY TRACT INFECTION	49/493 (9.9%)	71	38/187 (20.3%)	63	3/38 (7.9%)	8
URINARY TRACT INFECTION	47/493 (9.5%)	84	28/187 (15%)	54	3/38 (7.9%)	6
VIRAL UPPER RESPIRATORY TRACT INFECTION	3/493 (0.6%)	3	3/187 (1.6%)	3	2/38 (5.3%)	2
Injury, poisoning and procedural complications
FALL	7/493 (1.4%)	8	14/187 (7.5%)	20	1/38 (2.6%)	1
Investigations
ALANINE AMINOTRANSFERASE INCREASED	12/493 (2.4%)	15	4/187 (2.1%)	4	3/38 (7.9%)	4
ASPARTATE AMINOTRANSFERASE INCREASED	16/493 (3.2%)	17	5/187 (2.7%)	5	2/38 (5.3%)	3
BLOOD CREATINE PHOSPHOKINASE INCREASED	34/493 (6.9%)	44	17/187 (9.1%)	27	3/38 (7.9%)	4
Metabolism and nutrition disorders
HYPERCHOLESTEROLAEMIA	29/493 (5.9%)	35	17/187 (9.1%)	18	3/38 (7.9%)	3
Musculoskeletal and connective tissue disorders
RHEUMATOID ARTHRITIS	21/493 (4.3%)	32	21/187 (11.2%)	35	0/38 (0%)	0
Nervous system disorders
HEADACHE	18/493 (3.7%)	23	5/187 (2.7%)	7	3/38 (7.9%)	3
Renal and urinary disorders
NEPHROLITHIASIS	7/493 (1.4%)	10	1/187 (0.5%)	1	2/38 (5.3%)	3
RENAL COLIC	0/493 (0%)	0	2/187 (1.1%)	2	2/38 (5.3%)	3
Respiratory, thoracic and mediastinal disorders
COUGH	14/493 (2.8%)	14	10/187 (5.3%)	11	1/38 (2.6%)	2
Skin and subcutaneous tissue disorders
RASH	4/493 (0.8%)	4	5/187 (2.7%)	5	2/38 (5.3%)	2
ROSACEA	4/493 (0.8%)	4	2/187 (1.1%)	2	2/38 (5.3%)	2
Vascular disorders
HYPERTENSION	22/493 (4.5%)	23	19/187 (10.2%)	19	1/38 (2.6%)	1

Limitations/Caveats

[Not Specified]

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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.