Rheumatoid Arthritis
Conditions
Keywords
Musculoskeletal Disease, Arthritis, Joint Disease, Anti-inflammatory agents, Antirheumatic agents, ABT-494, upadacitinib
Brief summary
The study objective of Period 1 (Day 1 to Week 24) is to compare the safety and efficacy of upadacitinib 30 mg once daily (QD) and 15 mg QD versus placebo for the treatment of signs and symptoms of participants with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and had an inadequate response to or intolerance to at least 1 bDMARD. The study objective of Period 2 (Week 24 to Week 260) is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 15 mg QD and 30 mg QD in participants with RA who completed Period 1.
Detailed description
This study includes a 35-day screening period; a 24-week randomized, double-blind, parallel-group, placebo controlled treatment period (Period 1); a 236-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit). Period 1 consists of a 12-week double-blind, placebo-controlled treatment phase plus a 12-week double-blind phase where all participants were to receive upadacitinib; at Week 12 participants assigned to placebo will be switched to upadacitinib according to their randomization assignment. Participants who meet eligibility criteria will be randomized in a 2:2:1:1 ratio to one of four treatment groups: * Group 1: Upadacitinib 30 mg QD (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter) * Group 2: Upadacitinib 15 mg QD (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter) * Group 3: Placebo (Day 1 to Week 12) → upadacitinib 30 mg QD (Week 12 and thereafter) * Group 4: Placebo (Day 1 to Week 12) → upadacitinib 15 mg QD (Week 12 and thereafter) Participants will continue stable dose of csDMARD therapy for the first 24 weeks of the study. Participants who complete the Week 24 visit (end of Period 1) will enter the blinded long-term extension portion of the study, Period 2 and continue to receive the same dose of upadacitinib per original randomization assignment in a blinded manner. Starting at Week 24, at least 20% improvement in both swollen joint count (SJC) and tender joint count (TJC) compared to Baseline is required to remain on study drug. Starting at Week 24, initiation of or change in corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, or adding or increasing doses in up to 2 csDMARDs (concomitant use of up to 2 csDMARDs except the combination of methotrexate and leflunomide) is allowed as per local label. With the implementation of Protocol Amendment 4, all participants in the extension period will receive open-label upadacitinib 15 mg QD, including those currently on upadacitinib 30 mg QD.
Interventions
DRUGPlacebo
Tablet; Oral
DRUGUpadacitinib
Tablet; Oral
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of rheumatoid arthritis (RA) for≥ 3 months. * Treated for ≥ 3 months with ≥ 1 bDMARD therapy, but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration prior to the first dose of study drug. * Participant has been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug. The following csDMARDs are allowed: methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide. * Meets both of the following criteria: * ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. * hsCRP ≥ 3mg/L at Screening Visit.
Exclusion criteria
* Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib). * History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia \[currently with active symptoms\]). Current diagnosis of secondary Sjogren's Syndrome is permitted.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | Baseline and Week 12 | The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP). |
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 | Week 12 | The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 | Baseline and Week 12 | The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement. |
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | Baseline and Week 12 | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 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). |
| Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 | Baseline and Week 12 | The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity. |
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 | Baseline and week 1 | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP). |
| Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | Baseline and Week 12 | Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 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). |
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 | Baseline and Week 12 | The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement. |
Countries
Australia, Austria, Belgium, Canada, Czechia, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Latvia, New Zealand, Poland, Portugal, Puerto Rico, Russia, Slovakia, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at 152 sites located in 26 countries from March 2016 to January 2017. Eligible participants had active rheumatoid arthritis (RA) and previous inadequate response or intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARDs), and were receiving concomitant background conventional synthetic DMARDS (csDMARDs).
Pre-assignment details
Participants were randomized in a 1:1:2:2 ratio to one of the four treatment groups below. Randomization was stratified by the number of previous bDMARDs used and geographic region.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants received placebo once daily for 12 weeks. | 169 |
| Upadacitinib 15 mg Participants received upadacitinib 15 mg once daily for 12 weeks. | 164 |
| Upadacitinib 30 mg Participants received upadacitinib 30 mg once daily for 12 weeks. | 165 |
| Total | 498 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 1: Day 1 to Week 12 | Adverse Event | 2 | 2 | 1 | 12 |
| Period 1: Day 1 to Week 12 | Lost to Follow-up | 2 | 1 | 0 | 0 |
| Period 1: Day 1 to Week 12 | Other | 4 | 4 | 2 | 2 |
| Period 1: Day 1 to Week 12 | Randomized in Error | 0 | 0 | 1 | 0 |
| Period 1: Day 1 to Week 12 | Withdrawal by Subject | 2 | 1 | 4 | 2 |
| Period 1: Week 12 to Week 24 | Adverse Event | 1 | 2 | 2 | 5 |
| Period 1: Week 12 to Week 24 | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Period 1: Week 12 to Week 24 | Other | 1 | 0 | 1 | 4 |
| Period 1: Week 12 to Week 24 | Withdrawal by Subject | 1 | 0 | 1 | 4 |
| Period 2: Week 24 to Week 260 | Adverse Event | 11 | 9 | 21 | 11 |
| Period 2: Week 24 to Week 260 | Lack of Efficacy | 5 | 3 | 9 | 8 |
| Period 2: Week 24 to Week 260 | Lost to Follow-up | 1 | 5 | 9 | 6 |
| Period 2: Week 24 to Week 260 | Other | 8 | 5 | 15 | 15 |
| Period 2: Week 24 to Week 260 | Withdrawal by Subject | 11 | 10 | 17 | 10 |
Baseline characteristics
| Characteristic | Upadacitinib 15 mg | Total | Placebo | Upadacitinib 30 mg |
|---|---|---|---|---|
| Age, Continuous | 56.3 years STANDARD_DEVIATION 11.34 | 57.1 years STANDARD_DEVIATION 11.42 | 57.6 years STANDARD_DEVIATION 11.39 | 57.3 years STANDARD_DEVIATION 11.55 |
| Age, Customized 40 - 64 years | 115 Participants | 324 Participants | 106 Participants | 103 Participants |
| Age, Customized < 40 years | 11 Participants | 39 Participants | 14 Participants | 14 Participants |
| Age, Customized ≥ 65 years | 38 Participants | 135 Participants | 49 Participants | 48 Participants |
| Concomitant Conventional Synthetic DMARD Use at Baseline csDMARD other than methotrexate | 24 Participants | 82 Participants | 29 Participants | 29 Participants |
| Concomitant Conventional Synthetic DMARD Use at Baseline Methotrexate alone | 118 Participants | 364 Participants | 122 Participants | 124 Participants |
| Concomitant Conventional Synthetic DMARD Use at Baseline Methotrexate and other csDMARD | 19 Participants | 47 Participants | 17 Participants | 11 Participants |
| Concomitant Conventional Synthetic DMARD Use at Baseline Missing | 3 Participants | 5 Participants | 1 Participants | 1 Participants |
| Disease Activity Score 28 Based on CRP (DAS28[CRP]) | 5.9 units on a scale STANDARD_DEVIATION 0.95 | 5.8 units on a scale STANDARD_DEVIATION 0.95 | 5.8 units on a scale STANDARD_DEVIATION 1 | 5.8 units on a scale STANDARD_DEVIATION 0.89 |
| Duration of RA Diagnosis | 12.4 years STANDARD_DEVIATION 9.38 | 13.2 years STANDARD_DEVIATION 9.45 | 14.5 years STANDARD_DEVIATION 9.22 | 12.7 years STANDARD_DEVIATION 9.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 34 Participants | 86 Participants | 24 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 130 Participants | 412 Participants | 145 Participants | 137 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Geographic Region Asia | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Geographic Region Eastern Europe | 22 Participants | 67 Participants | 23 Participants | 22 Participants |
| Geographic Region North America | 109 Participants | 328 Participants | 110 Participants | 109 Participants |
| Geographic Region Other | 1 Participants | 5 Participants | 3 Participants | 1 Participants |
| Geographic Region Western Europe | 32 Participants | 97 Participants | 33 Participants | 32 Participants |
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | 1.7 units on a scale STANDARD_DEVIATION 0.64 | 1.6 units on a scale STANDARD_DEVIATION 0.61 | 1.6 units on a scale STANDARD_DEVIATION 0.6 | 1.6 units on a scale STANDARD_DEVIATION 0.59 |
| High-sensitivity C-reactive Protein (hsCRP) | 16.2 mg/L STANDARD_DEVIATION 18.62 | 16.2 mg/L STANDARD_DEVIATION 20.32 | 16.3 mg/L STANDARD_DEVIATION 21.1 | 16.0 mg/L STANDARD_DEVIATION 21.23 |
| Patient's Assessment of Pain | 68.2 mm STANDARD_DEVIATION 19.77 | 67.5 mm STANDARD_DEVIATION 20.52 | 68.9 mm STANDARD_DEVIATION 21.03 | 65.3 mm STANDARD_DEVIATION 20.67 |
| Patient's Global Assessment of Disease Activity | 67.2 mm STANDARD_DEVIATION 19.6 | 66.1 mm STANDARD_DEVIATION 21.15 | 66.3 mm STANDARD_DEVIATION 22.72 | 64.7 mm STANDARD_DEVIATION 21.05 |
| Physician's Global Assessment of Disease Activity | 68.7 mm STANDARD_DEVIATION 16.59 | 67.3 mm STANDARD_DEVIATION 16.39 | 66.9 mm STANDARD_DEVIATION 16.92 | 66.4 mm STANDARD_DEVIATION 15.63 |
| Prior Failed Biological Disease-modifying Anti-rheumatic Drugs (bDMARDs) Stratum 1 | 116 Participants | 344 Participants | 117 Participants | 111 Participants |
| Prior Failed Biological Disease-modifying Anti-rheumatic Drugs (bDMARDs) Stratum 2 | 48 Participants | 154 Participants | 52 Participants | 54 Participants |
| Race/Ethnicity, Customized American Indian/Alaska Native | 3 Participants | 7 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 9 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 17 Participants | 48 Participants | 21 Participants | 10 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 142 Participants | 433 Participants | 143 Participants | 148 Participants |
| Sex: Female, Male Female | 137 Participants | 418 Participants | 143 Participants | 138 Participants |
| Sex: Female, Male Male | 27 Participants | 80 Participants | 26 Participants | 27 Participants |
| Swollen Joint Count | 17.0 swollen joints STANDARD_DEVIATION 10.75 | 16.8 swollen joints STANDARD_DEVIATION 10.57 | 16.3 swollen joints STANDARD_DEVIATION 9.58 | 17.2 swollen joints STANDARD_DEVIATION 11.37 |
| Tender Joint Count | 27.8 tender joints STANDARD_DEVIATION 16.31 | 27.9 tender joints STANDARD_DEVIATION 15.58 | 28.5 tender joints STANDARD_DEVIATION 15.27 | 27.3 tender joints STANDARD_DEVIATION 15.23 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 169 | 0 / 164 | 1 / 165 | 9 / 236 | 5 / 240 | 2 / 138 |
| other Total, other adverse events | 68 / 169 | 68 / 164 | 78 / 165 | 196 / 236 | 203 / 240 | 59 / 138 |
| serious Total, serious adverse events | 0 / 169 | 9 / 164 | 12 / 165 | 87 / 236 | 71 / 240 | 21 / 138 |
Outcome results
Primary
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was low disease activity, based on a Disease Activity Score 28 (DAS28)-CRP score of ≤ 3.2 at Week 12. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.
Time frame: Week 12
Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom DAS28 data were missing at Week 12 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 | 14.2 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 | 43.3 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 | 42.4 percentage of participants |
p-value: <0.00195% CI: [19.9, 38.3]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [19, 37.4]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Time frame: Baseline and Week 12
Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 28.4 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 64.6 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 56.4 percentage of participants |
p-value: <0.00195% CI: [26.2, 46.2]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [17.8, 38.1]Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.
Time frame: Baseline and Week 12
Population: Full analysis set participants with available data at baseline; multiple imputation was used for missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 | -0.17 units on a scale |
| Upadacitinib 15 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 | -0.39 units on a scale |
| Upadacitinib 30 mg | Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 | -0.42 units on a scale |
p-value: <0.00195% CI: [-0.34, -0.1]ANCOVA
p-value: <0.00195% CI: [-0.38, -0.13]ANCOVA
Secondary
Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline in DAS28 (CRP) indicates improvement in disease activity.
Time frame: Baseline and Week 12
Population: Full analysis set participants with available data at baseline; multiple imputation was used for missing post-baseline data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 | -1.02 units on a scale |
| Upadacitinib 15 mg | Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 | -2.31 units on a scale |
| Upadacitinib 30 mg | Change From Baseline in in Disease Activity Score 28 (CRP) at Week 12 | -2.29 units on a scale |
p-value: <0.00195% CI: [-1.57, -1.01]ANCOVA
p-value: <0.00195% CI: [-1.56, -0.99]ANCOVA
Secondary
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Time frame: Baseline and Week 12
Population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Placebo | Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 | 2.39 units on a scale |
| Upadacitinib 15 mg | Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 | 5.83 units on a scale |
| Upadacitinib 30 mg | Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 | 7.02 units on a scale |
p-value: <0.00195% CI: [1.72, 5.15]Mixed Effect Model Repeat Measurement
p-value: <0.00195% CI: [2.89, 6.36]Mixed Effect Model Repeat Measurement
Secondary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Time frame: Baseline and week 1
Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 1 or for whom ACR data were missing at Week 1 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 | 10.7 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 | 27.4 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 | 24.8 percentage of participants |
p-value: <0.00195% CI: [8.5, 25.1]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [6.1, 22.3]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Time frame: Baseline and Week 12
Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 11.8 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 34.1 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 35.8 percentage of participants |
p-value: <0.00195% CI: [13.6, 31.1]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [15.1, 32.7]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Time frame: Baseline and Week 12
Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 6.5 percentage of participants |
| Upadacitinib 15 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 11.6 percentage of participants |
| Upadacitinib 30 mg | Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 23.0 percentage of participants |
p-value: 0.1195% CI: [-1.1, 11.2]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [9.1, 23.9]Cochran-Mantel-Haenszel