A Phase 3 interventional study of Placebo to Upadacitinib and Methotrexate in Rheumatoid Arthritis, sponsored by AbbVie. Completed at 290 sites in 45 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-07-07.
Sponsored by AbbVie · Phase 3, Interventional, and Treatment
The objectives of Period 1 were the following:
The objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib 7.5 mg QD (for participants in Japan only), 15 mg QD, and 30 mg QD in adults with RA who have completed Period 1.
This study includes 2 periods (a 48-week double-blind treatment period and a long-term extension period) and a Japan substudy. In Period 1 participants will be randomized in a 1:1:1 ratio to treatment Groups 2, 3, and 4 below, except for participants from Japan, who will be randomized in a 2:1:1:1 ratio to Groups 1, 2, 3, and 4:
Rescue therapy is defined for Weeks 12 through 24, Week 26, and Weeks 36 through 40. Starting at Week 12 through Week 24, participants who do not achieve ≥ 20% improvement in both tender joint count (TJC) and swollen joint count (SJC) compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: non-steroidal anti-inflammatory drug(s) (NSAIDs), corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days) and/or low-potency analgesics.
Rescue therapy for participants who meet the following criteria at Week 26 are as follows:
Participants who do not achieve clinical remission (CR) based on Clinical Disease Activity Index (CDAI) (defined as a CDAI score ≤ 2.8):
Starting at Week 36 through Week 40, participants who do not achieve ≥ 20% improvement in both TJC and SJC compared with baseline at two consecutive visits will continue on their blinded therapy and the Investigator should optimize (initiate or increase) background RA medications: NSAIDs, corticosteroids (oral ≤ 10 mg/day prednisone equivalent or prednisone equivalent ≤ 0.5 mg/kg/day for 3 consecutive days and up to 2 local injections), low-potency analgesics and csDMARDs (only 1 of the following: sulfasalazine, hydroxychloroquine or chloroquine).
Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension, Period 2 (212 weeks) and continue study treatment per assignment at the end of Period 1 in a blinded fashion. When the last participant completes the last visit of Period 1 (Week 48), study drug assignment in both periods may be unblinded, and participants will be dispensed study drug in an open-label fashion until the completion of Period 2. Starting with Protocol Amendment 6, participants receiving upadacitinib 15 mg and 30 mg QD will receive open-label upadacitinib 15 mg QD, and participants receiving methotrexate will receive open-label methotrexate.
A global analysis will be conducted for the comparisons of the primary and secondary efficacy endpoints between the upadacitinib 15 mg QD and 30 mg QD treatment groups versus the methotrexate treatment group for all participants (excluding the Japan specific upadacitinib 7.5 mg treatment group). Analyses will be conducted separately for United States (US)/Food and Drug Administration (FDA), European Union (EU)/European Medicines Agency (EMA), and Japan/Pharmaceuticals and Medical Devices Agency (PMDA) regulatory purposes, each according to a pre-specified sequence of primary and ranked secondary endpoints.
A separate Japan sub-study analysis will be conducted for the comparisons of the efficacy endpoints between the upadacitinib 7.5 mg QD, 15 mg QD, and 30 mg QD treatment groups versus the methotrexate treatment group for participants enrolled in Japan only.
3,554 studies on the registry are indexed under Arthritis; 317 are open to participants now.
This study's enrollment of 1,002 is above the median of 90 across 2,377 interventional studies indexed under Arthritis.
Browse Arthritis studies →AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.
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Participant meets both of the following minimum disease activity criteria:
-≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
Exclusion Criteria:
Period 1: Participants will receive placebo to upadacitinib once daily and methotrexate once weekly for 48 weeks. Period 2: Participants will continue on placebo to upadacitinib once daily and methotrexate once weekly until the study is unblinded, after which participants will receive open-label methotrexate up to Week 260.
Drug: Placebo to Upadacitinib · Drug: Methotrexate
Period 1: Participants will receive upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 7.5 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 7.5 mg up to Week 260.
Drug: Placebo to Methotrexate · Drug: Upadacitinib
Period 1: Participants will receive upadacitinib 15 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 15 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 15 mg up to Week 260.
Drug: Placebo to Methotrexate · Drug: Upadacitinib
Period 1: Participants will receive upadacitinib 30 mg once daily and placebo to methotrexate once weekly for 48 weeks. Period 2: Participants will continue on upadacitinib 30 mg once daily and placebo to methotrexate once weekly until the study is unblinded, after which participants will receive open-label upadacitinib 30 mg once daily. After implementation of Protocol Amendment 6 participants will receive upadacitinib 15 mg once daily up to Week 260.
Drug: Placebo to Methotrexate · Drug: Upadacitinib
Tablet; Oral
Capsule or Tablet; Oral
Capsule or Tablet; Oral
Tablet; Oral
Also known as: ABT-494, Rinvoq
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) 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
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis
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 24. 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 24
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis
The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) 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
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis
The second primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24. The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
Time frame: Baseline to Week 24
Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis
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 to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis
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 to week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis
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
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis
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 to week 12
Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis
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 to Week 24
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis
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 to Week 24
Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis
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 24
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis
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 24
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis
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 to Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis
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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. 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). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Time frame: Week 24
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis
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
Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis
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 24
Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis
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 24
Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study
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 With an ACR50 Response at Week 12 - Japan Sub-study
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
Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study
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
Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study
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 to Week 12
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study
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 to week 12
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study
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 to Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study
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 Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study
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 score less than 2.6 indicates clinical remission.
Time frame: Week 24
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study
The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
Time frame: Baseline to Week 24
Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study
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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. 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). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
Time frame: Week 24
Participants were randomized at 236 sites in 43 countries. The study included 2 periods and a Japan sub-study. The global study analysis included participants from Japan, but excluded the upadacitinib 7.5 mg group. The Japan sub-study included all participants from Japan, including the upadacitinib 7.5 mg group.
| Milestone | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Started | 315 | 55 | 317 | 315 |
| Received study drug | 314 | 55 | 317 | 314 |
| Global analysis population | 314 | 0 | 317 | 314 |
| Japan sub-study | 28 | 55 | 27 | 28 |
| Completed week 24 study drug | 268 | 51 | 290 | 282 |
| Received combination rescue therapy at week 26 | 37 | 3 | 19 | 9 |
| Completed | 256 | 51 | 277 | 271 |
| Not completed | 59 | 4 | 40 | 44 |
| Withdrew: Adverse event | 15 | 3 | 18 | 11 |
| Withdrew: Withdrawal by subject | 22 | 0 | 12 | 20 |
| Withdrew: Lost to follow-up | 4 | 0 | 6 | 5 |
| Withdrew: Lack of efficacy | 12 | 0 | 2 | 4 |
| Withdrew: Other | 5 | 1 | 2 | 3 |
| Withdrew: Not dosed | 1 | 0 | 0 | 1 |
| Milestone | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Started | 253 | 50 | 275 | 268 |
| Received study drug | 242 | 48 | 273 | 260 |
| Completed | 163 | 40 | 217 | 187 |
| Not completed | 90 | 10 | 58 | 81 |
| Withdrew: Adverse event | 16 | 4 | 11 | 26 |
| Withdrew: Withdrawal by subject | 32 | 5 | 23 | 27 |
| Withdrew: Lost to follow-up | 17 | 0 | 10 | 6 |
| Withdrew: Lack of efficacy | 11 | 0 | 1 | 1 |
| Withdrew: Coronavirus disease of 2019 (covid-19) infection | 0 | 0 | 0 | 3 |
| Withdrew: Covid-19 logistic restrictions | 0 | 0 | 2 | 1 |
| Withdrew: Other | 14 | 1 | 11 | 17 |
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 50% response (ACR50) 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).
| percentage of participants | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 - Global Analysis | 28.3 (23.4 to 33.3) | 52.1 (46.6 to 57.5) | 56.4 (50.9 to 61.9) |
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 24. 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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Global Analysis | 18.5 (14.2 to 22.8) | 48.3 (42.8 to 53.8) | 50.0 (44.5 to 55.5) |
The primary endpoint for Japan/Pharmaceuticals and Medical Devices Agency (PMDA) 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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 - Global Analysis | 54.1 (48.6 to 59.7) | 75.7 (71.0 to 80.4) | 77.1 (72.4 to 81.7) |
The second primary endpoint for Japan/PMDA regulatory purposes was change from baseline in mTSS at Week 24. The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
| units on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Global Analysis | 0.67 (0.43 to 0.90) | 0.14 (-0.09 to 0.37) | 0.07 (-0.16 to 0.31) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in DAS28 (CRP) at Week 12 - Global Analysis | -1.85 (-2.00 to -1.69) | -2.73 (-2.87 to -2.58) | -2.85 (-3.00 to -2.70) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Global Analysis | -0.49 (-0.55 to -0.42) | -0.83 (-0.90 to -0.76) | -0.86 (-0.93 to -0.79) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Global Analysis | 28.3 (23.4 to 33.3) | 53.3 (47.8 to 58.8) | 54.8 (49.3 to 60.3) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Global Analysis | 5.74 (4.84 to 6.64) | 9.99 (9.11 to 10.88) | 10.08 (9.19 to 10.98) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in DAS28 (CRP) at Week 24 - Global Analysis | -2.15 (-2.31 to -1.99) | -3.07 (-3.21 to -2.92) | -3.34 (-3.49 to -3.19) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 24 - Global Analysis | -0.60 (-0.67 to -0.52) | -0.87 (-0.94 to -0.80) | -0.91 (-0.98 to -0.84) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an ACR50 Response at Week 24 - Global Analysis | 33.4 (28.2 to 38.7) | 60.3 (54.9 to 65.6) | 65.6 (60.4 to 70.9) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 24 - Global Analysis | 32.2 (27.0 to 37.3) | 59.9 (54.5 to 65.3) | 65.0 (59.7 to 70.2) |
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.
| scores on a scale | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 24 - Global Analysis | 6.97 (6.03 to 7.91) | 10.70 (9.76 to 11.63) | 11.39 (10.42 to 12.36) |
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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. 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). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
| percentage of participants | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With No Radiographic Progression at Week 24 - Global Analysis | 77.7 (72.6 to 82.7) | 87.5 (83.6 to 91.3) | 89.3 (85.6 to 93.0) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 - Global Analysis | 14.0 (10.2 to 17.9) | 32.5 (27.3 to 37.6) | 36.9 (31.6 to 42.3) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an ACR20 Response at Week 24 - Global Analysis | 58.6 (53.2 to 64.0) | 78.9 (74.4 to 83.4) | 78.0 (73.4 to 82.6) |
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 | Methotrexate | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|
| Percentage of Participants With an ACR70 Response at Week 24 - Global Analysis | 18.5 (14.2 to 22.8) | 44.5 (39.0 to 49.9) | 49.7 (44.2 to 55.2) |
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 | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an ACR20 Response at Week 12 - Japan Sub-study | 57.1 (38.8 to 75.5) | 85.5 (76.1 to 94.8) | 85.2 (71.8 to 98.6) | 78.6 (63.4 to 93.8) |
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 | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an ACR50 Response at Week 12 - Japan Sub-study | 21.4 (6.2 to 36.6) | 60.0 (47.1 to 72.9) | 66.7 (48.9 to 84.4) | 71.4 (54.7 to 88.2) |
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 | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants With an ACR70 Response at Week 12 - Japan Sub-study | 0.0 (0.0 to 0.0) | 34.5 (22.0 to 47.1) | 51.9 (33.0 to 70.7) | 64.3 (46.5 to 82.0) |
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.
| scores on a scale | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Change From Baseline in DAS28 (CRP) at Week 12 - Japan Sub-study | -1.42 (-1.82 to -1.03) | -2.86 (-3.14 to -2.58) | -3.28 (-3.68 to -2.89) | -3.34 (-3.74 to -2.95) |
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.
| scores on a scale | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12 - Japan Sub-study | -0.20 (-0.37 to -0.04) | -0.75 (-0.86 to -0.63) | -0.95 (-1.12 to -0.78) | -0.95 (-1.12 to -0.79) |
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.
| scores on a scale | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12 - Japan Sub-study | 2.87 (0.56 to 5.18) | 8.84 (7.18 to 10.50) | 10.79 (8.48 to 13.09) | 9.63 (7.13 to 12.13) |
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 | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12 - Japan Sub-study | 17.9 (3.7 to 32.0) | 69.1 (56.9 to 81.3) | 77.8 (62.1 to 93.5) | 78.6 (63.4 to 93.8) |
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 score less than 2.6 indicates clinical remission.
| percentage of participants | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 24 - Japan Sub-study | 17.9 (3.7 to 32.0) | 67.3 (54.9 to 79.7) | 70.4 (53.1 to 87.6) | 82.1 (68.0 to 96.3) |
The mTSS measures the level of joint damage from radiographs of the hands and feet. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. Joint erosion was assessed in 16 joints in each hand/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 change from Baseline greater than 0 indicates progression.
| units on a scale | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Change From Baseline in Modified Total Sharp Score (mTSS) at Week 24 - Japan Sub-study | 2.64 (1.19 to 4.09) | 0.95 (-0.09 to 1.98) | 0.24 (-1.21 to 1.69) | 0.19 (-1.31 to 1.70) |
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. Joint erosion and joint space narrowing (JSN) were assessed by two independent, blinded readers. 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). The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst).
| percentage of participants | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg |
|---|---|---|---|---|
| Percentage of Participants With No Radiographic Progression at Week 24 - Japan Sub-study | 46.2 (27.0 to 65.3) | 82.4 (71.9 to 92.8) | 80.8 (65.6 to 95.9) | 79.2 (62.9 to 95.4) |
Collected over From first dose of study drug up to 30 days after last dose, maximum of 264 weeks; Adverse events (AEs) are reported for Weeks 1 to 24, Weeks 1 to 260, and After Switch for participants who transitioned from upadacitinib 30 mg QD to 15 mg QD after implementation of Protocol Amendment 6 in December 2019.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Weeks 1-24: Methotrexate Monotherapy | 1/314 (0.3%) | 13/314 (4.1%) | 159/314 (50.6%) |
| Weeks 1-24: Upadacitinib 7.5 mg Monotherapy | 0/55 (0%) | 5/55 (9.1%) | 38/55 (69.1%) |
| Weeks 1-24: Upadacitinib 15 mg Monotherapy | 2/317 (0.6%) | 16/317 (5%) | 169/317 (53.3%) |
| Weeks 1-24: Upadacitinib 30 mg Monotherapy | 3/314 (1%) | 20/314 (6.4%) | 174/314 (55.4%) |
| Weeks 1-260: Methotrexate Monotherapy | 8/314 (2.5%) | 49/314 (15.6%) | 234/314 (74.5%) |
| Weeks 1-260: Upadacitinib 7.5 mg Monotherapy | 1/55 (1.8%) | 13/55 (23.6%) | 52/55 (94.5%) |
| Weeks 1-260: Upadacitinib 15 mg Monotherapy | 6/317 (1.9%) | 68/317 (21.5%) | 242/317 (76.3%) |
| Weeks 1-260/Switch: Upadacitinib 30 mg Monotherapy | 9/314 (2.9%) | 71/314 (22.6%) | 256/314 (81.5%) |
| Weeks 1-260: Any Upadacitinib 7.5 mg | 1/56 (1.8%) | 15/56 (26.8%) | 55/56 (98.2%) |
| Weeks 1-260: Any Upadacitinib 15 mg | 6/335 (1.8%) | 88/335 (26.3%) | 272/335 (81.2%) |
| Weeks 1-260/Switch: Any Upadacitinib 30 mg | 10/332 (3%) | 79/332 (23.8%) | 277/332 (83.4%) |
| After Switch: Upadacitinib 15 mg Monotherapy | 5/181 (2.8%) | 28/181 (15.5%) | 100/181 (55.2%) |
| After Switch: Any Upadacitinib 15 mg | 7/218 (3.2%) | 35/218 (16.1%) | 126/218 (57.8%) |
| Event | Weeks 1-24: Methotrexate Monotherapy | Weeks 1-24: Upadacitinib 7.5 mg Monotherapy | Weeks 1-24: Upadacitinib 15 mg Monotherapy | Weeks 1-24: Upadacitinib 30 mg Monotherapy | Weeks 1-260: Methotrexate Monotherapy | Weeks 1-260: Upadacitinib 7.5 mg Monotherapy | Weeks 1-260: Upadacitinib 15 mg Monotherapy | Weeks 1-260/Switch: Upadacitinib 30 mg Monotherapy | Weeks 1-260: Any Upadacitinib 7.5 mg | Weeks 1-260: Any Upadacitinib 15 mg | Weeks 1-260/Switch: Any Upadacitinib 30 mg | After Switch: Upadacitinib 15 mg Monotherapy | After Switch: Any Upadacitinib 15 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| COVID-19 PNEUMONIAInfections and infestations | 0/314 | 0/55 | 0/317 | 0/314 | 1/314 | 0/55 | 2/317 | 2/314 | 0/56 | 3/335 | 2/332 | 8/181 | 12/218 |
| PYELONEPHRITIS ACUTEInfections and infestations | 0/314 | 1/55 | 0/317 | 0/314 | 0/314 | 2/55 | 0/317 | 0/314 | 2/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| PNEUMONIAInfections and infestations | 2/314 | 0/55 | 2/317 | 2/314 | 3/314 | 1/55 | 8/317 | 5/314 | 1/56 | 9/335 | 5/332 | 1/181 | 2/218 |
| CARDIAC TAMPONADECardiac disorders | 0/314 | 1/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| PERICARDITISCardiac disorders | 0/314 | 1/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| GASTRIC ULCER HAEMORRHAGEGastrointestinal disorders | 0/314 | 1/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| GASTRITISGastrointestinal disorders | 0/314 | 0/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| SALIVARY GLAND CALCULUSGastrointestinal disorders | 0/314 | 0/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| COVID-19Infections and infestations | 0/314 | 0/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 1/314 | 1/56 | 2/335 | 1/332 | 2/181 | 3/218 |
| KERATITIS BACTERIALInfections and infestations | 0/314 | 0/55 | 0/317 | 0/314 | 0/314 | 1/55 | 0/317 | 0/314 | 1/56 | 0/335 | 0/332 | 0/181 | 0/218 |
| Event | Weeks 1-24: Methotrexate Monotherapy | Weeks 1-24: Upadacitinib 7.5 mg Monotherapy | Weeks 1-24: Upadacitinib 15 mg Monotherapy | Weeks 1-24: Upadacitinib 30 mg Monotherapy | Weeks 1-260: Methotrexate Monotherapy | Weeks 1-260: Upadacitinib 7.5 mg Monotherapy | Weeks 1-260: Upadacitinib 15 mg Monotherapy | Weeks 1-260/Switch: Upadacitinib 30 mg Monotherapy | Weeks 1-260: Any Upadacitinib 7.5 mg | Weeks 1-260: Any Upadacitinib 15 mg | Weeks 1-260/Switch: Any Upadacitinib 30 mg | After Switch: Upadacitinib 15 mg Monotherapy | After Switch: Any Upadacitinib 15 mg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NASOPHARYNGITISInfections and infestations | 13/314 | 5/55 | 18/317 | 17/314 | 43/314 | 22/55 | 48/317 | 51/314 | 25/56 | 57/335 | 58/332 | 8/181 | 10/218 |
| HERPES ZOSTERInfections and infestations | 1/314 | 2/55 | 7/317 | 7/314 | 7/314 | 12/55 | 32/317 | 24/314 | 13/56 | 34/335 | 27/332 | 7/181 | 8/218 |
| PHARYNGITISInfections and infestations | 6/314 | 5/55 | 4/317 | 8/314 | 16/314 | 12/55 | 12/317 | 17/314 | 13/56 | 14/335 | 18/332 | 3/181 | 4/218 |
| INFLUENZAInfections and infestations | 1/314 | 2/55 | 1/317 | 3/314 | 7/314 | 8/55 | 5/317 | 9/314 | 10/56 | 9/335 | 11/332 | 2/181 | 2/218 |
| CONTUSIONInjury, poisoning and procedural complications | 2/314 | 1/55 | 2/317 | 2/314 | 8/314 | 8/55 | 10/317 | 5/314 | 10/56 | 11/335 | 5/332 | 3/181 | 5/218 |
| UPPER RESPIRATORY TRACT INFECTIONInfections and infestations | 14/314 | 3/55 | 20/317 | 23/314 | 31/314 | 9/55 | 49/317 | 43/314 | 9/56 | 59/335 | 51/332 | 5/181 | 7/218 |
| BLOOD CREATINE PHOSPHOKINASE INCREASEDInvestigations | 2/314 | 2/55 | 9/317 | 34/314 | 10/314 | 3/55 | 37/317 | 51/314 | 5/56 | 46/335 | 54/332 | 10/181 | 12/218 |
| BRONCHITISInfections and infestations | 6/314 | 0/55 | 7/317 | 5/314 | 24/314 | 7/55 | 22/317 | 27/314 | 9/56 | 33/335 | 29/332 | 5/181 | 7/218 |
| GASTROENTERITISInfections and infestations | 7/314 | 2/55 | 5/317 | 5/314 | 12/314 | 8/55 | 11/317 | 10/314 | 9/56 | 13/335 | 10/332 | 1/181 | 1/218 |
| HYPERTENSIONVascular disorders | 8/314 | 3/55 | 12/317 | 14/314 | 31/314 | 8/55 | 36/317 | 44/314 | 9/56 | 43/335 | 47/332 | 8/181 | 10/218 |
The full analysis set included all randomized participants who received at least 1 dose of study drug.
| Age, Continuous(years) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Mean | 53.3 ± 12.89 | 59.7 ± 13.8 | 51.9 ± 12.58 | 54.9 ± 12.58 | 53.7 ± 12.86 |
| Age, Customized(Participants) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| < 40 years | 50 | 5 | 60 | 34 | 149 |
| 40 - 65 years | 206 | 25 | 204 | 212 | 647 |
| ≥ 65 years | 58 | 25 | 53 | 68 | 204 |
| Sex: Female, Male(Participants) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Female | 240 | 36 | 241 | 240 | 757 |
| Male | 74 | 19 | 76 | 74 | 243 |
| Ethnicity (NIH/OMB)(Participants) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Hispanic or Latino | 102 | 0 | 107 | 107 | 316 |
| Not Hispanic or Latino | 212 | 55 | 210 | 207 | 684 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| White | 256 | 0 | 256 | 254 | 766 |
| Black or African American | 12 | 0 | 8 | 13 | 33 |
| American Indian/Alaska Native | 2 | 0 | 8 | 7 | 17 |
| Native Hawaiian or other Pacific Islander | 2 | 0 | 3 | 1 | 6 |
| Asian | 37 | 55 | 35 | 34 | 161 |
| Multiple | 5 | 0 | 7 | 5 | 17 |
| Geographic Region(Participants) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| North America | 46 | 0 | 48 | 46 | 140 |
| South/Central America | 90 | 0 | 91 | 91 | 272 |
| Western Europe | 37 | 0 | 36 | 36 | 109 |
| Eastern Europe | 85 | 0 | 87 | 87 | 259 |
| Asia-Japan | 28 | 55 | 27 | 28 | 138 |
| Asia - China | 1 | 0 | 1 | 1 | 3 |
| Asia - Other | 3 | 0 | 4 | 2 | 9 |
| Other | 24 | 0 | 23 | 23 | 70 |
| Duration of Rheumatoid Arthritis Diagnosis(years) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Mean | 2.6 ± 5.14 | 2.3 ± 5.77 | 2.9 ± 5.38 | 2.8 ± 5.63 | 2.7 ± 5.40 |
| Tender Joint Count(tender joints) | Methotrexate | Upadacitinib 7.5 mg | Upadacitinib 15 mg | Upadacitinib 30 mg | Total |
|---|---|---|---|---|---|
| Mean | 26.4 ± 16.15 | 18.0 ± 11.75 | 25.4 ± 14.42 | 25.2 ± 14.99 | 25.3 ± 15.12 |
8 further baseline measures are reported on the registry.
Showing the first 100 of 290 sites across 45 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
This study is completed, as verified in Jun 2023. You cannot join it, but the record below documents what was studied.
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