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A Study to Compare Upadacitinib (ABT-494) to Placebo in Adults With Rheumatoid Arthritis (RA) Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs

A Phase 2b/3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo in Japanese Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Dose of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) and Have an Inadequate Response to csDMARDs

Status
Completed
Phases
Phase 2Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02720523
Acronym
SELECTSUNRISE
Enrollment
197
Registered
2016-03-28
Start date
2016-03-22
Completion date
2022-06-07
Last updated
2023-06-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

rheumatoid arthritis, ABT-494, Japanese, Antirheumatic agents

Brief summary

This is a randomized, double-blind study comparing ABT-494 to placebo in Japanese participants with moderately to severely active rheumatoid arthritis who are on a stable dose of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and have an inadequate response. Following marketing approval of upadacitinib for rheumatoid arthritis in Japan, this study will become a post-marketing clinical study and include a long-term extension period.

Detailed description

This study consisted of a 35-day screening period; a 12-week randomized, double-blind, parallel-group, placebo-controlled treatment period (Period 1); a 248-week blinded long-term extension period (Period 2); and a 30-day follow-up period (call or visit). Participants who met eligibility criteria were randomized in a 3:3:3:1:1:1 ratio to one of six treatment groups: * Group 1: Upadacitinib 7.5 mg QD (Period 1) → upadacitinib 7.5 mg QD (Period 2) * Group 2: Upadacitinib 15 mg QD (Period 1) → upadacitinib 15 mg QD (Period 2) * Group 3: Upadacitinib 30 mg QD (Period 1) → upadacitinib 30 mg QD (Period 2) * Group 4: Placebo (Period 1) → upadacitinib 7.5 mg QD (Period 2) * Group 5: Placebo (Period 1) → upadacitinib 15 mg QD (Period 2) * Group 6: Placebo (Period 1) → upadacitinib 30 mg QD (Period 2)

Interventions

DRUGPlacebo

Tablet; Oral

DRUGUpadacitinib

Tablet; Oral

Sponsors

AbbVie
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Diagnosis of rheumatoid arthritis (RA) for \>= 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA. * Subjects have been receiving conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) therapy \>= 3 months and on a stable dose for \>= 4 weeks prior to the first dose of study drug. * Subject has \>= 6 swollen joints (based on 66 joint counts) and \>= 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits. * Subjects with prior exposure to at most one biological disease-modifying anti-rheumatic drug (bDMARD) may be enrolled (up to 20% of total number of subjects) after the required washout period. Specifically, prior to enrollment: 1. Subjects with limited exposure to bDMARD (\< 3 months) OR 2. Subjects who are responding to bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).

Exclusion criteria

* Prior exposure to any Janus kinase (JAK) inhibitor * Subjects who are considered inadequate responders (lack of efficacy) to bDMARD therapy, after minimum 3 months treatment, as determined by the Investigator. * History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis \[SpA\] including ankylosing spondylitis and non-radiographic axial SpA, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia \[currently with active symptoms\]). Current diagnosis of secondary Sjogren's Syndrome is permitted.

Design outcomes

Primary

MeasureTime frameDescription
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12Baseline and Week 12Participants 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).

Secondary

MeasureTime frameDescription
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12Baseline and Week 12Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12Baseline and Week 12The 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.
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12Baseline and Week 12Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12Baseline and Week 12The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12Week 12Low disease activity. was defined as a DAS28 score less than or equal to 3.2. 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.
Change From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12Baseline and Week 12The 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.
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1Baseline and Week 1Participants 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).
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 12Baseline and Week 12The 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 quality of life. A positive change from Baseline indicates improvement.
Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12Baseline and Week 12RA-WIS is a simple validated tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score \< 10 means low risk and no action is needed, scores between 10 and 17 indicate medium risk and appropriate advice and information should be given. If the score is \> 17, it means high risk and it could warrant referral. A negative change from Baseline indicates improvement.
Change From Baseline in the Severity of Morning Stiffness at Week 12Baseline and Week 12Morning stiffness severity was determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire. Participants rated the severity of morning stiffness on awakening over the past 7 days on a scale from 0 (No morning stiffness) to 10 (Worst possible morning stiffness).
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12Week 12Clinical remission was defined as a DAS28 (CRP) score less than 2.6. 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.

Countries

Japan

Participant flow

Recruitment details

Participants with active rheumatoid arthritis (RA) and an inadequate response to conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs) were enrolled at 49 sites in Japan. The study is currently ongoing, results are reported up to Week 60, as of the data cutoff date of 12 July 2018.

Pre-assignment details

Participants were randomized to 1 of 3 doses of upadacitinib or placebo in Period 1. Participants who completed week 12 could continue in the study; participants in the upadacitinib groups continued on the same dose of upadacitinib, participants in the placebo group switched to upadacitinib 7.5, 15, or 30 mg per the pre-specified randomization.

Participants by arm

ArmCount
Placebo
Participants randomized to receive placebo once daily for 12 weeks in Period 1.
49
Upadacitinib 7.5 mg
Participants randomized to receive upadacitinib 7.5 mg once daily for 12 weeks in Period 1.
49
Upadacitinib 15 mg
Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
49
Upadacitinib 30 mg
Participants randomized to receive upadacitinib 30 mg once daily for 12 weeks in Period 1.
50
Total197

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006
Period 1: Placebo-controlled PeriodAdverse Event0015000
Period 1: Placebo-controlled PeriodLack of Efficacy1000000
Period 1: Placebo-controlled PeriodOther0011000
Period 1: Placebo-controlled PeriodWithdrawal by Subject1000000
Period 2: Long-term Extension PeriodAdverse Event00004711
Period 2: Long-term Extension PeriodOngoing0000575445
Period 2: Long-term Extension PeriodOther0000203
Period 2: Long-term Extension PeriodWithdrawal by Subject0000211

Baseline characteristics

CharacteristicPlaceboUpadacitinib 7.5 mgUpadacitinib 15 mgUpadacitinib 30 mgTotal
Age, Continuous54.3 years
STANDARD_DEVIATION 13.04
55.8 years
STANDARD_DEVIATION 11.02
56.0 years
STANDARD_DEVIATION 12.5
54.7 years
STANDARD_DEVIATION 12.22
55.2 years
STANDARD_DEVIATION 12.14
Age, Customized
< 40 years
7 Participants5 Participants8 Participants3 Participants23 Participants
Age, Customized
45 to < 65 years
31 Participants32 Participants30 Participants34 Participants127 Participants
Age, Customized
≥ 65 years
11 Participants12 Participants11 Participants13 Participants47 Participants
Duration of RA Diagnosis4.8 years
STANDARD_DEVIATION 4.86
6.7 years
STANDARD_DEVIATION 7.15
5.9 years
STANDARD_DEVIATION 7.2
4.5 years
STANDARD_DEVIATION 4.3
5.5 years
STANDARD_DEVIATION 6.03
Health Assessment Questionnaire - Disability Index (HAQ-DI)1.0 units on a scale
STANDARD_DEVIATION 0.67
0.9 units on a scale
STANDARD_DEVIATION 0.67
1.0 units on a scale
STANDARD_DEVIATION 0.67
0.9 units on a scale
STANDARD_DEVIATION 0.6
0.9 units on a scale
STANDARD_DEVIATION 0.65
High-sensitivity C-reactive Protein (hsCRP)17.9 mg/L
STANDARD_DEVIATION 20.53
13.3 mg/L
STANDARD_DEVIATION 12.8
15.8 mg/L
STANDARD_DEVIATION 18.23
12.4 mg/L
STANDARD_DEVIATION 13.67
14.8 mg/L
STANDARD_DEVIATION 16.62
Patient's Assessment of Pain56.1 mm
STANDARD_DEVIATION 20.83
57.8 mm
STANDARD_DEVIATION 22.62
50.5 mm
STANDARD_DEVIATION 25.41
45.5 mm
STANDARD_DEVIATION 21.85
52.4 mm
STANDARD_DEVIATION 23.09
Patient's Global Assessment of Disease Activity53.8 mm
STANDARD_DEVIATION 21.72
59.0 mm
STANDARD_DEVIATION 22.51
49.3 mm
STANDARD_DEVIATION 24.89
47.8 mm
STANDARD_DEVIATION 22.79
52.4 mm
STANDARD_DEVIATION 23.25
Physician's Global Assessment of Disease Activity57.4 mm
STANDARD_DEVIATION 18.62
55.6 mm
STANDARD_DEVIATION 16.65
58.8 mm
STANDARD_DEVIATION 20.21
57.6 mm
STANDARD_DEVIATION 21.38
57.4 mm
STANDARD_DEVIATION 19.19
Prior Biological Disease-modifying Anti-rheumatic Drug (bDMARD) Use
No
46 Participants44 Participants43 Participants47 Participants180 Participants
Prior Biological Disease-modifying Anti-rheumatic Drug (bDMARD) Use
Yes
3 Participants5 Participants6 Participants3 Participants17 Participants
Race/Ethnicity, Customized
Japanese
49 Participants49 Participants49 Participants50 Participants197 Participants
Sex: Female, Male
Female
42 Participants34 Participants36 Participants43 Participants155 Participants
Sex: Female, Male
Male
7 Participants15 Participants13 Participants7 Participants42 Participants
Swollen Joint Count10.9 joints
STANDARD_DEVIATION 4.65
11.7 joints
STANDARD_DEVIATION 4.89
14.0 joints
STANDARD_DEVIATION 7.82
11.7 joints
STANDARD_DEVIATION 5.32
12.1 joints
STANDARD_DEVIATION 5.88
Tender Joint Count16.8 joints
STANDARD_DEVIATION 11.42
16.3 joints
STANDARD_DEVIATION 8.89
17.8 joints
STANDARD_DEVIATION 12.58
16.3 joints
STANDARD_DEVIATION 10.79
16.8 joints
STANDARD_DEVIATION 10.93

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
0 / 490 / 490 / 490 / 500 / 650 / 642 / 66
other
Total, other adverse events
11 / 4920 / 4915 / 4927 / 5055 / 6555 / 6460 / 66
serious
Total, serious adverse events
0 / 491 / 491 / 495 / 509 / 6514 / 6418 / 66

Outcome results

Primary

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).

Time frame: Baseline and Week 12

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1242.9 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1275.5 percentage of participants
Upadacitinib 15 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1283.7 percentage of participants
Upadacitinib 30 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1280.0 percentage of participants
p-value: <0.00195% CI: [14.3, 51]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [23.5, 58.1]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [19.4, 54.9]Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Armitage test
Secondary

Change From Baseline in Disease Activity Score 28 (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.

Time frame: Baseline and Week 12

Population: Full analysis set; multiple imputation was used for missing data.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12-0.79 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12-2.08 scores on a scale
Upadacitinib 15 mgChange From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12-2.39 scores on a scale
Upadacitinib 30 mgChange From Baseline in Disease Activity Score 28 (DAS28) (CRP) at Week 12-2.41 scores on a scale
p-value: <0.00195% CI: [-1.693, -0.88]ANCOVA
p-value: <0.00195% CI: [-2.005, -1.19]ANCOVA
p-value: <0.00195% CI: [-2.027, -1.216]ANCOVA
Secondary

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12

The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from Baseline in the overall score indicates improvement.

Time frame: Baseline and Week 12

Population: Full analysis set participants with available data at baseline; multiple imputation was used for missing data.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12-0.10 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12-0.41 scores on a scale
Upadacitinib 15 mgChange From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12-0.45 scores on a scale
Upadacitinib 30 mgChange From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12-0.49 scores on a scale
p-value: <0.00195% CI: [-0.465, -0.144]ANCOVA
p-value: <0.00195% CI: [-0.505, -0.184]ANCOVA
p-value: <0.00195% CI: [-0.55, -0.229]ANCOVA
Secondary

Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 12

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

Time frame: Baseline and Week 12

Population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 121.81 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 124.47 scores on a scale
Upadacitinib 15 mgChange From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 123.60 scores on a scale
Upadacitinib 30 mgChange From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) at Week 122.66 scores on a scale
p-value: 0.0495% CI: [0.12, 5.2]Mixed Effect Model Repeat Measurement
p-value: 0.16995% CI: [-0.77, 4.35]Mixed Effect Model Repeat Measurement
p-value: 0.51695% CI: [-1.73, 3.43]Mixed Effect Model Repeat Measurement
Secondary

Change From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12

RA-WIS is a simple validated tool to evaluate work instability (the consequence of a mismatch between an individual's functional ability and their work tasks). RA-WIS consists of 23 questions relating to the participant's functioning in their work environment, each answered as Yes or No. The total score is the number of questions answered Yes, and ranges from 0 to 23. A score \< 10 means low risk and no action is needed, scores between 10 and 17 indicate medium risk and appropriate advice and information should be given. If the score is \> 17, it means high risk and it could warrant referral. A negative change from Baseline indicates improvement.

Time frame: Baseline and Week 12

Population: Full analysis set participants who were working and with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.

ArmMeasureValue (GEOMETRIC_LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12-0.69 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12-3.22 scores on a scale
Upadacitinib 15 mgChange From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12-2.74 scores on a scale
Upadacitinib 30 mgChange From Baseline in Rheumatoid Arthritis Work Instability Scale (RA-WIS) at Week 12-2.24 scores on a scale
p-value: 0.02195% CI: [-4.68, -0.39]Mixed Effect Model Repeat Measurement
p-value: 0.0895% CI: [-4.36, 0.25]Mixed Effect Model Repeat Measurement
p-value: 0.2295% CI: [-4.06, 0.94]Mixed Effect Model Repeat Measurement
Secondary

Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12

The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.

Time frame: Baseline and Week 12

Population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 122.88 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 127.21 scores on a scale
Upadacitinib 15 mgChange From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 126.38 scores on a scale
Upadacitinib 30 mgChange From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 128.81 scores on a scale
p-value: <0.00195% CI: [2.1, 6.57]Mixed Effect Model Repeat Measurement
p-value: 0.00295% CI: [1.25, 5.75]Mixed Effect Model Repeat Measurement
p-value: <0.00195% CI: [3.64, 8.22]Mixed Effect Model Repeat Measurement
Secondary

Change From Baseline in the Severity of Morning Stiffness at Week 12

Morning stiffness severity was determined by the Patient's Assessment of Severity and Duration of Morning Stiffness questionnaire. Participants rated the severity of morning stiffness on awakening over the past 7 days on a scale from 0 (No morning stiffness) to 10 (Worst possible morning stiffness).

Time frame: Baseline and Week 12

Population: Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.

ArmMeasureValue (LEAST_SQUARES_MEAN)
PlaceboChange From Baseline in the Severity of Morning Stiffness at Week 12-1.02 scores on a scale
Upadacitinib 7.5 mgChange From Baseline in the Severity of Morning Stiffness at Week 12-2.83 scores on a scale
Upadacitinib 15 mgChange From Baseline in the Severity of Morning Stiffness at Week 12-2.84 scores on a scale
Upadacitinib 30 mgChange From Baseline in the Severity of Morning Stiffness at Week 12-2.98 scores on a scale
p-value: <0.00195% CI: [-2.57, -1.04]Mixed Effect Model Repeat Measurement
p-value: <0.00195% CI: [-2.59, -1.05]Mixed Effect Model Repeat Measurement
p-value: <0.00195% CI: [-2.73, -1.18]Mixed Effect Model Repeat Measurement
Secondary

Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12

Clinical remission was defined as a DAS28 (CRP) score less than 2.6. 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.

Time frame: Week 12

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom DAS28 data were missing at Week 12 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 126.1 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 1236.7 percentage of participants
Upadacitinib 15 mgPercentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 1257.1 percentage of participants
Upadacitinib 30 mgPercentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 1250.0 percentage of participants
p-value: <0.00195% CI: [15.5, 45.7]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [35.6, 66.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [28.5, 59.3]Cochran-Mantel-Haenszel
Secondary

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

Low disease activity. was defined as a DAS28 score less than or equal to 3.2. 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.

Time frame: Week 12

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom DAS28 data were missing at Week 12 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 1218.4 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 1253.1 percentage of participants
Upadacitinib 15 mgPercentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 1269.4 percentage of participants
Upadacitinib 30 mgPercentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 1272.0 percentage of participants
p-value: <0.00195% CI: [17, 52.4]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [34.2, 67.9]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [37.1, 70.1]Cochran-Mantel-Haenszel
Secondary

Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria: 1. ≥ 20% improvement in 68-tender joint count; 2. ≥ 20% improvement in 66-swollen joint count; and 3. ≥ 20% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).

Time frame: Baseline and Week 1

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 1 or for whom ACR data were missing at Week 1 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 18.2 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 130.6 percentage of participants
Upadacitinib 15 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 124.5 percentage of participants
Upadacitinib 30 mgPercentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 134.0 percentage of participants
p-value: 0.00695% CI: [7.4, 37.5]Cochran-Mantel-Haenszel
p-value: 0.02695% CI: [2.1, 30.6]Cochran-Mantel-Haenszel
p-value: 0.00295% CI: [10.6, 41]Cochran-Mantel-Haenszel
Secondary

Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria: 1. ≥ 50% improvement in 68-tender joint count; 2. ≥ 50% improvement in 66-swollen joint count; and 3. ≥ 50% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).

Time frame: Baseline and Week 12

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 1216.3 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 1240.8 percentage of participants
Upadacitinib 15 mgPercentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 1265.3 percentage of participants
Upadacitinib 30 mgPercentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 1258.0 percentage of participants
p-value: 0.00795% CI: [7.3, 41.7]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [32.1, 65.9]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [24.5, 58.8]Cochran-Mantel-Haenszel
Secondary

Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria: 1. ≥ 70% improvement in 68-tender joint count; 2. ≥ 70% improvement in 66-swollen joint count; and 3. ≥ 70% improvement in at least 3 of the 5 following parameters: * Physician global assessment of disease activity * Patient global assessment of disease activity * Patient assessment of pain * Health Assessment Questionnaire - Disability Index (HAQ-DI) * High-sensitivity C-reactive protein (hsCRP).

Time frame: Baseline and Week 12

Population: Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 122.0 percentage of participants
Upadacitinib 7.5 mgPercentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 1220.4 percentage of participants
Upadacitinib 15 mgPercentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 1234.7 percentage of participants
Upadacitinib 30 mgPercentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 1228.0 percentage of participants
p-value: 0.00495% CI: [6.4, 30.3]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [18.7, 46.6]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [12.9, 39]Cochran-Mantel-Haenszel

Source: ClinicalTrials.gov · Data processed: Feb 24, 2026