A Phase 3 interventional study of Placebo for Adalimumab and Adalimumab in Rheumatoid Arthritis, sponsored by AbbVie. Active, not recruiting at 370 sites in 44 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-05.
Sponsored by AbbVie · Phase 3, Interventional, and Treatment
The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.
This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2).
Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups:
Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response.
Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48.
Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48.
Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.
2,888 studies on the registry are indexed under Arthritis, Rheumatoid; 390 are open to participants now.
This study's enrollment of 1,629 is above the median of 94 across 1,984 interventional studies indexed under Arthritis, Rheumatoid.
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Exclusion Criteria:
Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1). Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.
Drug: Placebo for Adalimumab · Drug: Placebo for Upadacitinib · Drug: Upadacitinib
Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index \[CDAI\] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.
Drug: Adalimumab · Drug: Placebo for Upadacitinib · Drug: Upadacitinib
Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48. Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.
Drug: Placebo for Adalimumab · Drug: Adalimumab · Drug: Upadacitinib
Administered by subcutaneous injection once every other week
Administered by subcutaneous injection once every other week
Also known as: Humira
Tablets taken orally once a day
Tablets taken orally once a day
Also known as: ABT-494
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
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of \< 2.6 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 2.6 indicates clinical remission.
Time frame: Week 12
Change From Baseline in DAS28 (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
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score. Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.
Time frame: Baseline and Week 26
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
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
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
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
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 (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(CRP) score less than or equal to 3.2 indicates low disease activity.
Time frame: Week 12
Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
Time frame: Week 12
Change From Baseline in Duration of Morning Stiffness at Week 12
Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Change From Baseline in Patient's Assessment of Pain at Week 12
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
Time frame: Baseline and Week 12
Percentage of Participants With No Radiographic Progression at Week 26
No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst). Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
Time frame: Baseline and Week 26
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
Participants with moderately to severely active rheumatoid arthritis (RA) on a stable dose of methotrexate with an inadequate response were randomized at 286 study sites in 41 countries. This study is currently ongoing; results are reported as of the data cut-off date of 02 February 2018, when all participants were to have completed Week 26.
| Milestone | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Started | 651 | 327 | 651 |
| Received assigned study drug | 651 | 327 | 650 |
| Completed week 14 on study drug | 620 | 300 | 620 |
| Rescued at week 14 | 231 | 56 | 78 |
| Rescued at week 18 | 48 | 14 | 29 |
| Rescued at week 22 | 26 | 7 | 18 |
| Completed | 595 | 288 | 600 |
| Not completed | 56 | 39 | 51 |
| Withdrew: Adverse event | 17 | 20 | 22 |
| Withdrew: Withdrawal by subject | 22 | 11 | 15 |
| Withdrew: Lost to follow-up | 7 | 4 | 5 |
| Withdrew: Lack of efficacy | 4 | 0 | 1 |
| Withdrew: Other | 6 | 4 | 8 |
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 | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | 36.4 (32.7 to 40.1) | 63.0 (57.8 to 68.2) | 70.5 (67.0 to 74.0) |
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of \< 2.6 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 2.6 indicates clinical remission.
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 | 6.1 (4.3 to 8.0) | 18.0 (13.9 to 22.2) | 28.7 (25.2 to 32.2) |
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.
| units on a scale | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in DAS28 (CRP) at Week 12 | -1.15 (-1.276 to -1.017) | -2.01 (-2.175 to -1.848) | -2.48 (-2.608 to -2.347) |
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score. Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.
| units on a scale | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26 | 0.92 (0.64 to 1.20) | 0.10 (-0.25 to 0.46) | 0.24 (-0.04 to 0.53) |
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.
| units on a scale | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 | -0.28 (-0.339 to -0.227) | -0.49 (-0.556 to -0.415) | -0.60 (-0.653 to -0.538) |
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).
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 | 14.9 (12.2 to 17.6) | 29.1 (24.1 to 34.0) | 45.2 (41.3 to 49.0) |
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.
| units on a scale | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 | 3.56 (2.79 to 4.33) | 6.27 (5.31 to 7.23) | 7.89 (7.11 to 8.68) |
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 (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(CRP) score less than or equal to 3.2 indicates low disease activity.
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 | 13.8 (11.2 to 16.5) | 28.7 (23.8 to 33.7) | 45.0 (41.2 to 48.8) |
Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10. CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12 | 16.3 (13.4 to 19.1) | 30.0 (25.0 to 34.9) | 40.4 (36.6 to 44.2) |
Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
| minutes | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in Duration of Morning Stiffness at Week 12 | -48.59 (-58.84 to -38.34) | -82.71 (-95.80 to -69.62) | -92.63 (-103.03 to -82.23) |
The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
| units on a scale | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) | 4.81 (3.85 to 5.77) | 7.44 (6.25 to 8.64) | 8.95 (7.98 to 9.93) |
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
| mm | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Change From Baseline in Patient's Assessment of Pain at Week 12 | -15.46 (-17.63 to -13.29) | -25.31 (-28.16 to -22.47) | -31.76 (-33.96 to -29.56) |
No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst). Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst). Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants With No Radiographic Progression at Week 26 | 76.0 (72.5 to 79.4) | 86.8 (83.0 to 90.7) | 83.5 (80.5 to 86.5) |
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).
| percentage of participants | Placebo | Adalimumab | Upadacitinib |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 | 4.9 (3.3 to 6.6) | 13.5 (9.8 to 17.2) | 24.9 (21.6 to 28.2) |
Collected over From first dose of study drug up to Week 26, or up to 30 days after last dose for those receiving placebo or upadacitinib who discontinued prior to Week 26, or up to 70 days after last dose for those receiving adalimumab who discontinued prior to Week 26.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo | 2/652 (0.3%) | 19/652 (2.9%) | 43/652 (6.6%) |
| Adalimumab | 2/327 (0.6%) | 14/327 (4.3%) | 16/327 (4.9%) |
| Upadacitinib | 0/650 (0%) | 24/650 (3.7%) | 72/650 (11.1%) |
| Placebo / Upadacitinib | 0/304 (0%) | 7/304 (2.3%) | 9/304 (3%) |
| Adalimumab / Upadacitinib | 0/77 (0%) | 0/77 (0%) | 6/77 (7.8%) |
| Upadacitinib / Adalimumab | 0/125 (0%) | 2/125 (1.6%) | 4/125 (3.2%) |
| Event | Placebo | Adalimumab | Upadacitinib | Placebo / Upadacitinib | Adalimumab / Upadacitinib | Upadacitinib / Adalimumab |
|---|---|---|---|---|---|---|
| PULMONARY EMBOLISMRespiratory, thoracic and mediastinal disorders | 1/652 | 3/327 | 1/650 | 0/304 | 0/77 | 0/125 |
| PNEUMONIAInfections and infestations | 0/652 | 0/327 | 0/650 | 0/304 | 0/77 | 1/125 |
| VAGINAL HAEMORRHAGEReproductive system and breast disorders | 0/652 | 0/327 | 0/650 | 0/304 | 0/77 | 1/125 |
| CELLULITISInfections and infestations | 0/652 | 2/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| GASTROENTERITISInfections and infestations | 3/652 | 0/327 | 2/650 | 0/304 | 0/77 | 0/125 |
| ACUTE MYOCARDIAL INFARCTIONCardiac disorders | 0/652 | 0/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| FOOD POISONINGGastrointestinal disorders | 0/652 | 0/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| SEPSISInfections and infestations | 1/652 | 1/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| FALLInjury, poisoning and procedural complications | 0/652 | 1/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| RHEUMATOID ARTHRITISMusculoskeletal and connective tissue disorders | 1/652 | 0/327 | 0/650 | 1/304 | 0/77 | 0/125 |
| Event | Placebo | Adalimumab | Upadacitinib | Placebo / Upadacitinib | Adalimumab / Upadacitinib | Upadacitinib / Adalimumab |
|---|---|---|---|---|---|---|
| URINARY TRACT INFECTIONInfections and infestations | 0/652 | 0/327 | 0/650 | 9/304 | 6/77 | 4/125 |
| UPPER RESPIRATORY TRACT INFECTIONInfections and infestations | 24/652 | 7/327 | 37/650 | 0/304 | 0/77 | 0/125 |
| NASOPHARYNGITISInfections and infestations | 19/652 | 9/327 | 36/650 | 0/304 | 0/77 | 0/125 |
The full analysis set consisted of all randomized participants who received at least 1 dose of study drug (placebo, adalimumab, or upadacitinib).
| Age, Continuous(years) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| Mean | 53.6 ± 12.24 | 53.7 ± 11.70 | 54.2 ± 12.08 | 53.9 ± 12.07 |
| Age, Customized(Participants) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| < 40 years | 91 | 39 | 81 | 211 |
| 40 to 64 years | 437 | 232 | 439 | 1108 |
| ≥ 65 years | 123 | 56 | 131 | 310 |
| Sex: Female, Male(Participants) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| Female | 512 | 259 | 521 | 1292 |
| Male | 139 | 68 | 130 | 337 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| Hispanic or Latino | 206 | 106 | 215 | 527 |
| Not Hispanic or Latino | 445 | 221 | 436 | 1102 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| White | 561 | 292 | 576 | 1429 |
| Black or African American | 38 | 17 | 33 | 88 |
| American Indian/Alaska Native | 2 | 1 | 1 | 4 |
| Native Hawaiian or other Pacific Islander | 1 | 0 | 0 | 1 |
| Asian | 39 | 15 | 31 | 85 |
| Multiple | 10 | 2 | 10 | 22 |
| Geographic Region(Participants) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| North America | 121 | 60 | 122 | 303 |
| South/Central America | 173 | 86 | 173 | 432 |
| Western Europe | 35 | 19 | 35 | 89 |
| Eastern Europe | 262 | 132 | 262 | 656 |
| Asia | 21 | 10 | 21 | 52 |
| Other | 39 | 20 | 38 | 97 |
| Duration of Rheumatoid Arthritis Diagnosis(years) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| Mean | 8.3 ± 8.00 | 8.3 ± 8.41 | 8.1 ± 7.73 | 8.2 ± 7.97 |
| Tender Joint Count(tender joints) | Placebo | Adalimumab | Upadacitinib | Total |
|---|---|---|---|---|
| Mean | 26.0 ± 14.30 | 26.4 ± 15.16 | 26.4 ± 15.15 | 26.2 ± 14.81 |
7 further baseline measures are reported on the registry.
Showing the first 100 of 370 sites across 44 countries.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting information: Study protocol, Sap, Csr, Analytic code
This study is active, not recruiting, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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