A Study Comparing Upadacitinib (ABT-494) to Placebo and t... | NCT02629159 | Trialant
NCT02629159
Sponsor
AbbVie
Status
Active, not recruiting
Last Update Posted
Aug 5, 2025Actual
Enrollment
1,629Actual
Phase
Phase 3
Conditions
Rheumatoid Arthritis
Interventions
Placebo for Adalimumab
Adalimumab
Placebo for Upadacitinib
Upadacitinib
Countries
United States
Argentina
Australia
Austria
Belarus
Belgium
Bosnia and Herzegovina
Brazil
Bulgaria
Canada
Chile
Colombia
Croatia
Czechia
Denmark
Estonia
France
Germany
Greece
Hong Kong
Hungary
Ireland
Israel
Italy
Kazakhstan
Latvia
Lithuania
Malaysia
Mexico
New Zealand
Poland
Portugal
Puerto Rico
Romania
Russia
Serbia
Slovakia
South Africa
South Korea
Spain
Taiwan
Turkey (Türkiye)
Ukraine
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT02629159
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
M14-465
Secondary IDs
ID
Type
Description
Link
2022-501017-31-00
Other Identifier
EU CT
Brief Title
A Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Adults With Rheumatoid Arthritis Who Are on a Stable Dose of Methotrexate and Who Have an Inadequate Response to Methotrexate
Official Title
A Phase 3, Randomized, Double-Blind Study Comparing Upadacitinib (ABT-494) to Placebo and to Adalimumab in Subjects With Moderately to Severely Active Rheumatoid Arthritis Who Are on a Stable Background of Methotrexate (MTX) and Who Have an Inadequate Response to MTX (MTX-IR)
Acronym
SELECT-COMPARE
Organization
AbbVieINDUSTRY
Status Module
Record Verification Date
Aug 2025
Overall Recruitment Status or Expanded Access Status
Active, not recruiting
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 1, 2015Actual
Primary Completion Date
Oct 27, 2017Actual
Completion Date
Sep 30, 2027Estimated
First Submitted Date
Dec 10, 2015
First Submission Date that Met QC Criteria
Dec 10, 2015
First Posted Date
Dec 14, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Sep 13, 2019
Results First Submitted that Met QC Criteria
Sep 13, 2019
Results First Posted Date
Oct 7, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 1, 2018
Certification/Extension First Submitted that Passed QC Review
Oct 1, 2018
Certification/Extension First Posted Date
Oct 3, 2018Actual
Last Update Submitted Date
Aug 1, 2025
Last Update Posted Date
Aug 5, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
AbbVieINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
No
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study was to assess efficacy, including inhibition of radiographic progression, and safety with upadacitinib versus placebo and versus an active comparator, adalimumab, in adults with with moderately to severely active rheumatoid arthritis (RA) who are on a stable background of methotrexate (MTX and who have an inadequate response to MTX.
Detailed Description
This study consists of a 48-week double-blind treatment period (Period 1) and a long-term extension period (Period 2).
Period 1 is a 48-week randomized, double-blind, parallel-group, placebo-controlled and active comparator-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo, and versus adalimumab. Participants will be randomized in a 2:2:1 ratio to one of three treatment groups:
Placebo (up to Week 26)
Upadacitinib 15 mg once daily (QD)
Adalimumab 40 mg every other week (eow)
Participants randomized to placebo who do not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib treatment. At Week 26, all participants still receiving placebo will be switched to blinded upadacitinib treatment regardless of clinical response.
Participants randomized to adalimumab who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded upadacitinib. Participants still receiving adalimumab at Week 26 who do not achieve low disease activity (LDA) according to Clinical Disease Activity Index (CDAI; LDA is defined as CDAI ≤ 10) will be switched to blinded upadacitinib treatment to Week 48.
Participants randomized to upadacitinib who do not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline will be switched to blinded adalimumab; participants still receiving upadacitinib at Week 26 who do not achieve LDA (CDAI ≤ 10) will be switched to blinded adalimumab treatment to Week 48.
Participants who complete the Week 48 visit (end of Period 1) will enter the long-term extension phase of the study (Period 2), for up to 5 years. Participants will continue study treatment as assigned at the end of Period 1. Starting at the Week 48 and thereafter, at least 20% improvement in both TJC and SJC compared to Baseline is required to remain on study drug. Anyone who does not fulfill this criterion at 2 consecutive visits (starting at Week 48) will be discontinued.
Conditions Module
Conditions
Rheumatoid Arthritis
Keywords
Musculoskeletal disease
Arthritis
Joint disease
Anti-inflammatory agents
Antirheumatic agents
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
1,629Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo followed by ABT-494
Placebo Comparator
Participants were to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were to be switched to 15 mg upadacitinib QD until Week 48 (end of Period 1).
Participants who complete Period 1 will continue to receive 15 mg upadacitinib orally QD for up to 5 years in Period 2.
Drug: Placebo for Adalimumab
Drug: Placebo for Upadacitinib
Drug: Upadacitinib
Adalimumab
Active Comparator
Participants were to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index [CDAI] ≤ 10) were to be switched to 15 mg upadacitinib orally QD until Week 48.
Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.
Drug: Adalimumab
Drug: Placebo for Upadacitinib
Drug: Upadacitinib
Upadacitinib
Experimental
Participants were to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were to be switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were to be switched to 40 mg adalimumab eow until Week 48.
Participants who complete Period 1 will continue to receive the same treatment assigned at the end of Period 1 (15 mg upadacitinib QD or 40 mg adalimumab eow) for up to 5 years in Period 2.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo for Adalimumab
Drug
Administered by subcutaneous injection once every other week
Placebo followed by ABT-494
Upadacitinib
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
≥ 20% improvement in 68-tender joint count;
≥ 20% improvement in 66-swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 12.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
Week 12
Secondary Outcomes
Measure
Description
Time Frame
Change From Baseline in DAS28 (CRP) at Week 12
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Adult male or female, at least 18 years old.
Diagnosis of RA for greater than or equal to 3 months.
Subjects must have been on oral or parenteral methotrexate (MTX) therapy greater than or equal to 3 months and on a stable prescription of greater than or equal to 15 to 25 mg/week (or greater than or equal to 10 mg/week in subjects intolerant of MTX at doses greater than or equal to 12.5 mg/week) for at least 4 weeks prior to the first dose of study drug. In addition all subjects should take a dietary supplement of folic acid or folinic acid throughout the study participation.
Meets the following minimum disease activity criteria: greater than or equal to 6 swollen joints (based on 66 joint counts) and greater than or equal to 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.
At least one of the following at Screening: greater than or equal to 3 bone erosions on x-ray OR greater than or equal to 1 bone erosion and a positive rheumatoid factor OR greater than or equal to 1 bone erosion and a positive anti-cyclic citrullinated peptide autoantibodies.
Subjects with prior exposure to only one biological disease-modifying anti-rheumatic drugs (bDMARD) (except adalimumab) may be enrolled (up to 20% of total study population) if they have documented evidence of intolerance to the bDMARD or limited exposure (less than 3 months), but required washout periods need to be satisfied.
Except for MTX, subject must have discontinued all conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
Exclusion Criteria:
Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).
Subjects who have been exposed to adalimumab or who are considered inadequate responders to bDMARD therapy as determined by the Investigator.
History of inflammatory joint disease other than RA. History of secondary Sjogren's Syndrome is permitted.
Fleischmann R, Pangan AL, Song IH, Mysler E, Bessette L, Peterfy C, Durez P, Ostor AJ, Li Y, Zhou Y, Othman AA, Genovese MC. Upadacitinib Versus Placebo or Adalimumab in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate: Results of a Phase III, Double-Blind, Randomized Controlled Trial. Arthritis Rheumatol. 2019 Nov;71(11):1788-1800. doi: 10.1002/art.41032. Epub 2019 Aug 28.
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.
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
Participants were randomized in a 2:1:2 ratio to receive placebo, adalimumab, or upadacitinib. Randomization was stratified by prior exposure to biologic disease-modifying anti-rheumatic drug(s) (bDMARD) (yes/no) and geographic region.
Rescue therapy was offered to participants who met protocol-specified criteria at Weeks 14, 18, 22, or 26.
Recruitment Details
Participants with moderately to severely active rheumatoid arthritis (RA) on a stable dose of methotrexate with an inadequate response were randomized at 286 study sites in 41 countries.
This study is currently ongoing; results are reported as of the data cut-off date of 02 February 2018, when all participants were to have completed Week 26.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo
Participants randomized to receive placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD. At Week 26, all remaining participants were switched to 15 mg upadacitinib QD.
Administered by subcutaneous injection once every other week
Adalimumab
Upadacitinib
Humira
Placebo for Upadacitinib
Drug
Tablets taken orally once a day
Adalimumab
Placebo followed by ABT-494
Upadacitinib
Drug
Tablets taken orally once a day
Adalimumab
Placebo followed by ABT-494
Upadacitinib
ABT-494
Baseline and Week 12
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.
Baseline and Week 26
Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability.
A negative change from Baseline in the overall score indicates improvement.
Baseline and Week 12
Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:
≥ 50% improvement in 68-tender joint count;
≥ 50% improvement in 66-swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12
The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).
The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.
Baseline and Week 12
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.
Week 12
Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.
CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
Week 12
Change From Baseline in Duration of Morning Stiffness at Week 12
Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
Baseline and Week 12
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
Baseline and Week 12
Change From Baseline in Patient's Assessment of Pain at Week 12
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
Baseline and Week 12
Percentage of Participants With No Radiographic Progression at Week 26
No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst).
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
Baseline and Week 26
Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:
≥ 70% improvement in 68-tender joint count;
≥ 70% improvement in 66-swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
Baseline and Week 12
Mesa
Arizona
85202
United States
SunValley Arthritis Center, Lt /ID# 143123
Peoria
Arizona
85381
United States
Elite Clinical Studies, LLC /ID# 144881
Phoenix
Arizona
85018
United States
AZ Arthritis and Rheum Researc /ID# 143080
Phoenix
Arizona
85032-9306
United States
AZ Arthritis and Rheum Researc /ID# 143121
Phoenix
Arizona
85032-9306
United States
AZ Arthritis & Rheuma Research /ID# 143131
Phoenix
Arizona
85032
United States
Arizona Research Center, Inc. /ID# 144877
Phoenix
Arizona
85053-4061
United States
AZ Arthritis & Rheum Research /ID# 156093
Sun City
Arizona
85351
United States
University of Arizona Cancer Center - North Campus /ID# 143114
Tucson
Arizona
85719-1478
United States
Osteoporosis Medical Center /ID# 153935
Beverly Hills
California
90211
United States
T. Joseph Raoof, MD, Inc. /ID# 144884
Encino
California
91436
United States
Rheumatology Ctr of San Diego /ID# 153747
Escondido
California
92025
United States
C.V. Mehta MD, Med Corporation /ID# 143116
Hemet
California
92543
United States
Allergy and Rheum Med Clin /ID# 146083
La Jolla
California
92037
United States
Kotha and Kotha /ID# 161046
La Mesa
California
91942
United States
TriWest Research Associates- La Mesa /ID# 143115
La Mesa
California
91942
United States
Valerius Med Grp & Res Ctr /ID# 143120
Los Alamitos
California
90720-5402
United States
Discovery MM Services, Inc /ID# 163504
Los Angeles
California
11373
United States
Desert Medical Advances /ID# 143097
Palm Desert
California
92260
United States
Sierra Rheumatology /ID# 155672
Roseville
California
95661
United States
Robin K. Dore MD, Inc /ID# 143090
Tustin
California
92780
United States
Medvin Clinical Research /ID# 148362
Whittier
California
90606
United States
Arthritis Assoc & Osteo Ctr /ID# 143122
Colorado Springs
Colorado
80920
United States
Arthritis and Rheum Clin N. CO /ID# 156094
Fort Collins
Colorado
80528
United States
AARDS Research, Inc. /ID# 154190
Aventura
Florida
33180
United States
ZASA Clinical Research /ID# 143134
Boynton Beach
Florida
33472
United States
Clinical Res of West FL, Inc. /ID# 143112
Clearwater
Florida
33765
United States
International Medical Research /ID# 143132
Daytona Beach
Florida
32117
United States
Lakes Research, LLC /ID# 145630
Miami
Florida
33014
United States
FL Med Ctr and Research, Inc. /ID# 143081
Miami
Florida
33142
United States
Ctr Arthritis & Rheumatic Dise /ID# 143135
Miami
Florida
33173
United States
Precision Research Org, LLC /ID# 143092
Miami Lakes
Florida
33016-1501
United States
Advanced Clin Res of Orlando /ID# 154617
Ocoee
Florida
34761-4547
United States
Rheum Assoc of Central FL /ID# 145632
Orlando
Florida
32806
United States
Omega Research Consultants /ID# 145635
Orlando
Florida
32810
United States
HMD Research LLC /ID# 163292
Orlando
Florida
32819
United States
Arthritis Research of Florida /ID# 143125
Palm Harbor
Florida
34684-2672
United States
Arthritis Center, Inc. /ID# 145647
Palm Harbor
Florida
34684
United States
St. Anthony Comprehsve Res Ins /ID# 143095
St. Petersburg
Florida
33705
United States
Clinical Research West FL /ID# 148358
Tampa
Florida
33603
United States
SW FL Clin Res Ctr, Tampa, FL /ID# 143117
Tampa
Florida
33609
United States
BayCare Medical Group, Inc. /ID# 143085
Tampa
Florida
33614-7101
United States
Lovelace Scientific Resources /ID# 143106
Venice
Florida
34292
United States
Arthritis and Rheumatology /ID# 155668
Atlanta
Georgia
30342
United States
Arthritis Center of North GA /ID# 155258
Gainesville
Georgia
30501
United States
North Georgia Rheumatology Grp /ID# 147170
Lawrenceville
Georgia
30045
United States
Advanced Clinical Research /ID# 153090
Meridian
Idaho
83642
United States
Great Lakes Clinical Trials /ID# 148357
Chicago
Illinois
60640
United States
Arthritis Treatment Center /ID# 155260
Frederick
Maryland
21204
United States
The Center for Rheumatology & /ID# 151356
Wheaton
Maryland
20902
United States
Clinical Pharmacology Study Gr /ID# 143082
Worcester
Massachusetts
01605
United States
Advanced Rheumatology, PC /ID# 143118
Lansing
Michigan
48910
United States
Shores Rheumatology, PC /ID# 162977
Saint Clair Shores
Michigan
48081
United States
St. Luke's Hospital /ID# 156750
Duluth
Minnesota
55805
United States
North Mississippi Med Clinics /ID# 145636
Tupelo
Mississippi
38801
United States
Physician Res. Collaboration /ID# 143087
Lincoln
Nebraska
68516
United States
Quality Clinical Research Inc. /ID# 156394
Omaha
Nebraska
68114
United States
Atlantic Coast Research /ID# 148355
Toms River
New Jersey
08755
United States
Ocean Rheumatology, PA /ID# 143111
Toms River
New Jersey
08755
United States
Arthritis Rheumatic Back Disorder /ID# 143102
Voorhees Township
New Jersey
08043
United States
Albuquerque Clinical Trials, Inc /ID# 143083
Albuquerque
New Mexico
87102
United States
Arthritis and Osteo Assoc /ID# 143127
Las Cruces
New Mexico
88011
United States
St. Lawrence Health System /ID# 161619
Potsdam
New York
13676
United States
Joint & Muscle Research Instit /ID# 143119
Charlotte
North Carolina
28204
United States
DJL Clinical Research, PLLC /ID# 143101
Charlotte
North Carolina
28210-8508
United States
EmergeOrtho, P.A. /ID# 143100
Durham
North Carolina
27704
United States
Cape Fear Arthritis Care /ID# 148361
Leland
North Carolina
28451
United States
Coastal Carolina Health Care /ID# 148359
New Bern
North Carolina
28562
United States
Shanahan Rheuma & Immuno /ID# 145643
Raleigh
North Carolina
27617
United States
Clinical Research Solutions, LLC /ID# 154619
Dayton
Ohio
45409
United States
Arthritis Assoc of NW Ohio /ID# 143094
Toledo
Ohio
43606
United States
Healthcare Research Consultant /ID# 143129
Tulsa
Oklahoma
74135
United States
Altoona Ctr Clinical Res /ID# 143110
Duncansville
Pennsylvania
16635
United States
Clinical Research Ctr Reading /ID# 143133
Wyomissing
Pennsylvania
19610
United States
Columbia Arthritis Center /ID# 153730
Columbia
South Carolina
29204
United States
Innovative Clinical Research /ID# 145637
Greenville
South Carolina
29601
United States
Articularis Healthcare Group, Inc d/b/a Low Country Rheumatology /ID# 143091
Summerville
South Carolina
29486-7887
United States
Arthritis Associates, PLLC /ID# 155490
Kingsport
Tennessee
37660
United States
Rheumatology Consultants, PLLC /ID# 153731
Knoxville
Tennessee
37909
United States
Dr. Ramesh Gupta /ID# 143099
Memphis
Tennessee
38119
United States
Austin Regional Clinic /ID# 143084
Austin
Texas
78731
United States
Diagnostic Group Integrated He /ID# 148356
Beaumont
Texas
77701
United States
Arthritis Care and Diagnostic /ID# 150677
Dallas
Texas
75231
United States
Metroplex Clinical Research /ID# 145631
Dallas
Texas
75231
United States
Doctor's Hosp at Renaissance /ID# 154616
Edinburg
Texas
78539
United States
MedResearch Inc. /ID# 154618
El Paso
Texas
79935
United States
Accurate Clinical Management /ID# 145644
Houston
Texas
77004
United States
Accurate Clinical Research /ID# 145645
Houston
Texas
77034
United States
Rheumatology Clinic of Houston /ID# 150921
Houston
Texas
77065
United States
Houston Institute for Clin Res /ID# 144879
Houston
Texas
77074
United States
Pioneer Research Solutions, Inc. /ID# 145640
Houston
Texas
77098-5294
United States
Arthritis Consultants, P.A. /ID# 144880
Killeen
Texas
76549
United States
Arthritis & Osteoporosis Assoc /ID# 147364
Lubbock
Texas
79424
United States
P&I Clinical Research /ID# 161625
Lufkin
Texas
75904-3132
United States
SW Rheumatology Res. LLC /ID# 143126
Mesquite
Texas
75150
United States
Discovery MM Services, Inc. /ID# 162578
Missouri City
Texas
77459-4750
United States
Discovery MM Services, Inc. /ID# 163183
Missouri City
Texas
77459-4750
United States
Discovery MM Services, Inc. /ID# 163184
Missouri City
Texas
77459-4750
United States
Sun Research Institute /ID# 159539
San Antonio
Texas
78215
United States
Accurate Clinical Management /ID# 143089
San Antonio
Texas
78229
United States
Arthritis & Osteo Ctr of S. TX /ID# 143103
San Antonio
Texas
78232
United States
DM Clinical Research /ID# 151357
Tomball
Texas
77375
United States
Arthritis Clinic of N. VA, P.C /ID# 143109
Arlington
Virginia
22205
United States
Ctr for Arth and Rheum Disease /ID# 143113
Chesapeake
Virginia
23320
United States
Arthritis Northwest, PLLC /ID# 143088
Spokane
Washington
99204
United States
The Vancouver Clinic, INC. PS /ID# 143107
Vancouver
Washington
98664
United States
West Virginia Research Inst /ID# 153088
South Charleston
West Virginia
25309
United States
Rheumatology and Immunotherapy Center /ID# 145646
Franklin
Wisconsin
53132
United States
Aprillus Asistencia e Investig /ID# 148406
Capital Federal
Buenos Aires
1046
Argentina
Mautalen Salud e Investigacion /ID# 142843
Buenos Aires
1128
Argentina
Fundacion Sanatorio Guemes /ID# 148405
Buenos Aires
1180
Argentina
Consultorio Reumatologic Pampa /ID# 144853
Buenos Aires
1428
Argentina
Cemic /Id# 148404
Buenos Aires
1431
Argentina
Org Medica de Investigacion /ID# 144855
Buenos Aires
C1015ABO
Argentina
Inst. Rheumatologic Strusberg /ID# 145601
Córdoba
5000
Argentina
Consultora Integral de Salud S /ID# 144856
Córdoba
5900
Argentina
Instituto CAICI /ID# 144854
Rosario, Santa FE
2000
Argentina
Cordis S.A. /Id# 152622
Salta
4400
Argentina
Iari /Id# 151293
San Fernando
1646
Argentina
Centro Integral de Reumatologi /ID# 142845
San Miguel de Tucumán
4000
Argentina
Centro Medico Privado/Reuma /ID# 142842
San Miguel de Tucumán
4000
Argentina
Centro de Enfermedades /ID# 153542
Santa Fe
2000
Argentina
Royal Prince Alfred Hospital /ID# 144857
Camperdown
New South Wales
2050
Australia
Emeritus Research /ID# 142848
Camberwell
Victoria
3124
Australia
LKH-Univ. Klinikum Graz /ID# 142851
Graz
8036
Austria
First City Clinical Hospital /ID# 158011
Minsk
220013
Belarus
Cliniques Universitaires Saint Luc /ID# 142858
Woluwe-Saint-Lambert
Brussels Capital
1200
Belgium
Rhumaconsult SPRL /ID# 142860
Charleroi
Hainaut
6000
Belgium
CHU de Liege /ID# 148401
Liège
Liege
4000
Belgium
UZ Gent /ID# 142859
Ghent
Oost-Vlaanderen
9000
Belgium
CHU Ambroise Pare /ID# 152953
Mons
7000
Belgium
University Clinical Centre of the Republic of Srpska /ID# 142862
Banja Luka
Republika Srpska
78000
Bosnia and Herzegovina
University Clinical Centre of the Republic of Srpska /ID# 142863
Banja Luka
Republika Srpska
78000
Bosnia and Herzegovina
Clinical Center University of Sarajevo /ID# 142865
Sarajevo
71000
Bosnia and Herzegovina
CIP - Centro Internacional de Pesquisa /ID# 142872
Goiânia
Goiás
74110-120
Brazil
Hc Ufmg /Id# 142868
Belo Horizonte
Minas Gerais
30130-100
Brazil
Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 142871
Curitiba
Paraná
80030-110
Brazil
Hospital de Clinicas de Porto Alegre /ID# 142870
Porto Alegre
Rio Grande do Sul
90035-903
Brazil
LMK Sevicos Medicos S/S /ID# 142869
Porto Alegre
Rio Grande do Sul
90480-000
Brazil
CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 142867
São Paulo
São Paulo
04266-010
Brazil
CCBR Brasil /ID# 150918
Rio de Janeiro
22271-100
Brazil
MHAT Trimontsium /ID# 142874
Plovdiv
4000
Bulgaria
UMHAT Pulmed OOD /ID# 142877
Plovdiv
4000
Bulgaria
MHAT Kaspela /ID# 142873
Plovdiv
4001
Bulgaria
Diagnostic Consultative Center /ID# 142875
Sofia
1612
Bulgaria
UMHAT Sv. Ivan Rilski /ID# 142876
Sofia
1612
Bulgaria
Manitoba Clinic /ID# 161434
Winnipeg
Manitoba
R3A IM3
Canada
Ciads /Id# 142880
Winnipeg
Manitoba
R3N 0K6
Canada
St. Clare's Mercy Hospital /ID# 142879
St. John's
Newfoundland and Labrador
A1C 5B8
Canada
Adachi Medicine Prof. Corp /ID# 154205
Hamilton
Ontario
L8N 1Y2
Canada
CA Ctr for Clin Trials CCCT /ID# 157379
Thornhill
Ontario
L4J 1W3
Canada
Groupe de Recherche en Maladies Osseuses /ID# 142878
Sainte-Foy
Quebec
G1V 3M7
Canada
Ctr de Inv Clinica del Sur /ID# 142888
Temuco
Araucania
4781156
Chile
Reg. Clinical Hosptial Concepcion /ID# 151271
Concepción
4070038
Chile
Corp de Beneficencia Osorno /ID# 147941
Osorno
1710216
Chile
Someal /Id# 144704
Providencia-santiago
7510186
Chile
Quantum Research LTDA. /ID# 142893
Puerto Varas
5550170
Chile
Quantum Research Stgo. /ID# 157933
Santiago
7500588
Chile
Soc. de Prestaciones medicas y Paramedicas Goecke /ID# 142890
Santiago
7510047
Chile
Clinica DermaCross /ID# 142892
Santiago
7640881
Chile
Investigaciones Medicas SSMSO /ID# 151686
Santiago
8207257
Chile
Centro Inter Estud Clin CIEC /ID# 144777
Santiago
8420383
Chile
Centro Medico de Reumatologia /ID# 148402
Temuco
4790928
Chile
Cinvec /Id# 144705
Viña del Mar
2520997
Chile
Centro de Investigacion en Reumatologia y Especialidades Medicas- CIREEM SAS /ID# 142898
Bogota
Cundinamarca
110221
Colombia
Ctr Int de Reum del Caribe SAS /ID# 142894
Barranquilla
80002
Colombia
Fund Inst de Reum F. Chalem /ID# 149847
Bogota DC
Colombia
Riesgo de Fractura S.A - CAYRE /ID# 142896
Bogotá
110221
Colombia
Medicity S.A.S. /ID# 144860
Bucaramanga
680003
Colombia
Centro Integral de Reumatologi /ID# 142897
Medellín
50021
Colombia
Klinicki bolnicki centar Rijeka /ID# 160232
Rijeka
Primorje-Gorski Kotar County
51000
Croatia
Klinicki bolnicki centar Split /ID# 152530
Split
21000
Croatia
Clinical Hospital Dubrava /ID# 142900
Zagreb
10000
Croatia
Medical Center Kuna-Peric /ID# 142901
Zagreb
10000
Croatia
Poliklinika Bonifarm /ID# 142899
Zagreb
10000
Croatia
L.K.N. Arthrocentrum, s.r.o /ID# 145961
Hlučín
Moravian-Silesian Region
748 01
Czechia
CTCenter MaVe, s.r.o. /ID# 142905
Olomouc
Olomouc Region
779 00
Czechia
Revmatologicky ustav Praha /ID# 142904
Prague
Praha 2
128 00
Czechia
Nuselská poliklinika, Revmatologie /ID# 144862
Prague
Praha 4
140 00
Czechia
Revmatologická ambulance /ID# 145963
Prague
Praha 4
140 00
Czechia
Thomayerova nemocnice /ID# 145962
Prague
Praha 4
140 00
Czechia
REVMACLINIC s.r.o. /ID# 142906
Brno
611 41
Czechia
Revmatologie Bruntal, s.r.o /ID# 142903
Bruntál
79201
Czechia
Revmatologicka a interni ambul /ID# 142907
Kladno
272 01
Czechia
Revmatologie MUDr. Klara Sirov /ID# 142908
Ostrava
702 00
Czechia
Arthromed, s.r.o. /ID# 144706
Pardubice
530 02
Czechia
Aarhus University Hospital /ID# 158838
Aarhus N
Central Jutland
8200
Denmark
Regionhospital Silkeborg /ID# 142914
Silkeborg
8600
Denmark
Center of Clinical and Basic Research /ID# 142922
Tallinn
Harju
10128
Estonia
MediTrials /ID# 151870
Tartu
Tartu
50406
Estonia
Paernu Hospital /ID# 142921
Pärnu
80010
Estonia
East Tallinn Central Hospital /ID# 142923
Tallinn
10138
Estonia
North Estonian Medical Centre /ID# 145454
Tallinn
13419
Estonia
Hopital Universitaire Purpan /ID# 144707
Toulouse
Haute-Garonne
31059
France
CHRU Lille - Hôpital Claude Huriez /ID# 151312
Lille
Hauts-de-France
59045
France
Hopital Saint Eloi /ID# 142925
Montpellier
Herault
34295
France
CHU Bordeaux-Hopital Pellegrin /ID# 145618
Bordeaux
33076
France
Hopital de la Cote de Nacre /ID# 145616
Caen
14033
France
CHU Gabriel Montpied /ID# 145619
Clermont-Ferrand
63000
France
Hopital de la Conception /ID# 142926
Marseille
13005
France
Hopital Pitie Salpetriere /ID# 145605
Paris
75651
France
CHU de Rennes - Hospital Sud /ID# 151957
Rennes
35203
France
CHU Strasbourg Hautepierre Hos /ID# 144708
Strasbourg
67200
France
Uniklinik Koln /ID# 145964
Cologne
North Rhine-Westphalia
50937
Germany
Rheumazentrum Ruhrgebiet /ID# 145620
Herne
North Rhine-Westphalia
44649
Germany
Praxis Walter, Rendsburg /ID# 142932
Rendsburg
Schleswig-Holstein
24768
Germany
Med Versorgungszentrum AGILOME /ID# 154975
Chemnitz
9126
Germany
Rheumaforschungszentrum II /ID# 142930
Hamburg
20095
Germany
LMU Klinikum der Universität München /ID# 142931
Munich
80337
Germany
General Hospital of Athens Laiko /ID# 142934
Athens
Attica
115 27
Greece
University General Hospital Attikon /ID# 142933
Athens
Attica
12462
Greece
General Hospital of Athens Ippokratio /ID# 142935
Athens
11527
Greece
Queen Mary Hospital /ID# 142938
Hong Kong
999077
Hong Kong
Tuen Mun Hospital /ID# 142939
Tuenmen
999077
Hong Kong
CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 142951
Miskolc
Borsod-Abauj Zemplen county
3529
Hungary
Qualiclinic Kft. /ID# 142953
Budapest III
Pest County
1036
Hungary
Markusovszky Egyetemi Oktatókórház /ID# 145621
Szombathely
Vas County
9700
Hungary
Vital Medical Center Orvosi es /ID# 145950
Veszprém
Veszprém megye
8200
Hungary
Budai Irgalmasrendi Korhaz /ID# 142952
Budapest
1023
Hungary
Revita Reumatologiai Rendelo /ID# 142950
Budapest
1027
Hungary
Synexus Magyarorszag Kft. /ID# 153061
Budapest
1036
Hungary
Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz /ID# 142948
Debrecen
4031
Hungary
Hevizgyogyfurdo es Szent Andra /ID# 142949
Hévíz
8380
Hungary
Kiskunhalasi Semmelweis Korhaz /ID# 151944
Kiskunhalas
6400
Hungary
Pest Megyei Flor Ferenc Korhaz /ID# 142954
Kistarcsa
2143
Hungary
St Vincent's University Hosp /ID# 142957
Dublin
D04 T6F4
Ireland
Tel Aviv Sourasky Medical Ctr /ID# 144709
Tel Aviv
Tel Aviv
6423906
Israel
Rambam Health Care Campus /ID# 152050
Haifa
3109601
Israel
Bnai Zion Medical Center /ID# 151958
Haifa
3339419
Israel
The Lady Davis Carmel MC /ID# 142960
Haifa
3436212
Israel
Sheba Medical Center /ID# 145965
Ramat Gan
5262100
Israel
Istituto Clinico Humanitas /ID# 147528
Rozzano
Milano
20089
Italy
AOU Citta della Salute Scienza /ID# 150070
Turin
Piedmont
10126
Italy
Azienda Ospedaliera Luigi Sacc /ID# 142966
Milan
20157
Italy
A.O.U.I. di Verona Policlinico /ID# 142963
Verona
37134
Italy
JSC Nat Scientific Med Res Ctr /ID# 142971
Astana
010009
Kazakhstan
Karaganda State Medical Univ /ID# 153433
Karaganda
100008
Kazakhstan
Semey State Medical University /ID# 152659
Semey
071403
Kazakhstan
Regional Clinical Hospital /ID# 147168
Shymkent
160000
Kazakhstan
LTD M+M Centers /ID# 142984
Adazi
2164
Latvia
Daugavpils Regional Hospital /ID# 142982
Daugavpils
5417
Latvia
D.Saulites-Kandevicas PP /ID# 142985
Liepāja
3401
Latvia
Clinic ORTO /ID# 142983
Riga
1005
Latvia
Riga East Clinical Univ Hosp /ID# 142981
Riga
1038
Latvia
Hosp Lithuanian Univ Health Sc /ID# 142986
Kaunas
Kaunas County
50009
Lithuania
Vilnius University Hospital /ID# 142987
Vilnius
LT-08661
Lithuania
Hospital Raja Perempuan Zainab II /ID# 157862
Kota Bharu
Kelantan
15586
Malaysia
Hospital Selayang /ID# 156756
Batu Caves
68100
Malaysia
Hospital Umum Sarawak /ID# 142990
Kuching
93586
Malaysia
Hospital Putrajaya /ID# 142989
Putrajaya
62250
Malaysia
Hospital Tuanku Ja afar /ID# 142988
Seremban
70300
Malaysia
Clinstile, S.A. de C.V. /ID# 144866
Cuauhtémoc
Mexico City
06700
Mexico
Hosp. Univ. Dr. Jose E. Gonz /ID# 142992
Monterrey
Nuevo León
64320
Mexico
Invest y Biomed de Chihuahua /ID# 142996
Chihuahua City
31000
Mexico
RM Pharma Specialists, S.A de C.V /ID# 142994
Mexico City
03100
Mexico
Hospital de Jesús Nazareno /ID# 142993
Mexico City
06090
Mexico
Centro Peninsular de Investiga /ID# 148159
Mérida
97000
Mexico
Waikato Hospital /ID# 143002
Hamilton
Waikato Region
3204
New Zealand
Porter Rheumatology Ltd /ID# 143001
Nelson
7010
New Zealand
Timaru Medical Specialists Ltd /ID# 143000
Timaru
7910
New Zealand
NZOZ Nasz Lekarz /ID# 143004
Torun
Kuyavian-Pomeranian Voivodeship
87-100
Poland
Malopolskie Centrum Kliniczne /ID# 152782
Cracow
Lesser Poland Voivodeship
30-149
Poland
Pratia MCM Krakow /ID# 143005
Krakow
Lesser Poland Voivodeship
30-510
Poland
WroMedica I. Bielicka, A. Strzalkowska s.c. /ID# 145622
Wroclaw
Lower Silesian Voivodeship
51-685
Poland
REUMED Sp.z o.o. Filia nr 1 /ID# 148189
Lublin
Lublin Voivodeship
20-607
Poland
McBk Sc /Id# 143003
Grodzisk Mazowiecki
Masovian Voivodeship
05-825
Poland
Centralny Szpital Kliniczny MSWiA w Warszawie /ID# 151960
Warsaw
Masovian Voivodeship
02-507
Poland
Centrum Medyczne AMED Warszawa Targowek /ID# 157621
Warsaw
Masovian Voivodeship
03-291
Poland
Osteo-Medic spolka cywilna /ID# 143006
Bialystok
Podlaskie Voivodeship
15-351
Poland
Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163293
Gdynia
Pomeranian Voivodeship
81-384
Poland
Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163294
Gdynia
Pomeranian Voivodeship
81-384
Poland
Synexus Polska Sp. z o.o. Oddz. Poznan /ID# 163295
Fleischmann R, Swierkot J, Durez P, Bessette L, Blanco R, Van den Bosch F, Geem D, Luo L, Smith LD, Caballero D, Meerwein S, Peterfy C, Tanaka Y, Mysler E. Long-term safety and efficacy of upadacitinib compared with adalimumab in patients with rheumatoid arthritis: 7-year data from the SELECT-COMPARE study. RMD Open. 2026 Jun 24;12(2):e006657. doi: 10.1136/rmdopen-2025-006657.
Winthrop KL, Klaff J, Penn SK, Liu Y, Garcia C, Mysler E, Wells AF, Bu X, Fish I, Chen M, Cunningham AL. Immunogenicity of adjuvanted recombinant zoster vaccine in patients with rheumatoid arthritis treated with upadacitinib: 60-week results from a randomised controlled trial substudy. RMD Open. 2025 Aug 12;11(3):e005521. doi: 10.1136/rmdopen-2025-005521.
Gossec L, Patel J, Kadakia A, Fang S, Peng Y, Strengholt S, Taylor PC, Ostor A. Association between rapid and sustained remission and clinician- and patient-reported outcomes in patients with rheumatoid arthritis: post hoc analysis of data from the SELECT-COMPARE study. Arthritis Res Ther. 2025 Jun 13;27(1):123. doi: 10.1186/s13075-025-03580-1.
Fleischmann R, Swierkot J, Penn SK, Durez P, Bessette L, Bu X, Khan N, Li Y, Peterfy CG, Tanaka Y, Mysler E. Long-term safety and efficacy of upadacitinib versus adalimumab in patients with rheumatoid arthritis: 5-year data from the phase 3, randomised SELECT-COMPARE study. RMD Open. 2024 May 28;10(2):e004007. doi: 10.1136/rmdopen-2023-004007.
Fleischmann R, Blanco R, Van den Bosch F, Bessette L, Song Y, Penn SK, McDearmon-Blondell E, Khan N, Chan K, Mysler E. Long-term Efficacy and Safety Following Switch Between Upadacitinib and Adalimumab in Patients with Rheumatoid Arthritis: 5-Year Data from SELECT-COMPARE. Rheumatol Ther. 2024 Jun;11(3):599-615. doi: 10.1007/s40744-024-00658-1. Epub 2024 Mar 18.
Rubbert-Roth A, Kakehasi AM, Takeuchi T, Schmalzing M, Palac H, Coombs D, Liu J, Anyanwu SI, Lippe R, Curtis JR. Malignancy in the Upadacitinib Clinical Trials for Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, and Non-radiographic Axial Spondyloarthritis. Rheumatol Ther. 2024 Feb;11(1):97-112. doi: 10.1007/s40744-023-00621-6. Epub 2023 Nov 20.
Fleischmann R, Curtis JR, Charles-Schoeman C, Mysler E, Yamaoka K, Richez C, Palac H, Dilley D, Liu J, Strengholt S, Burmester G. Safety profile of upadacitinib in patients at risk of cardiovascular disease: integrated post hoc analysis of the SELECT phase III rheumatoid arthritis clinical programme. Ann Rheum Dis. 2023 Sep;82(9):1130-1141. doi: 10.1136/ard-2023-223916. Epub 2023 Jun 12.
Conaghan PG, Pavelka K, Hsieh SC, Bonnington TL, Kent TC, Marchbank K, Edwards CJ. Evaluating the efficacy of upadacitinib in patients with moderate rheumatoid arthritis: a post-hoc analysis of the SELECT phase 3 trials. Rheumatol Adv Pract. 2023 Feb 8;7(1):rkad017. doi: 10.1093/rap/rkad017. eCollection 2023.
Kakehasi AM, Radominski SC, Baravalle MD, Palazuelos FCI, Garcia-Garcia C, Arruda MS, Curi M, Liu J, Qiao M, Velez-Sanchez P, Vargas JI. Safety of upadacitinib in Latin American patients with rheumatoid arthritis: an integrated safety analysis of the SELECT phase 3 clinical program. Clin Rheumatol. 2023 May;42(5):1249-1258. doi: 10.1007/s10067-023-06513-y. Epub 2023 Jan 30.
Bergman M, Buch MH, Tanaka Y, Citera G, Bahlas S, Wong E, Song Y, Zueger P, Ali M, Strand V. Routine Assessment of Patient Index Data 3 (RAPID3) in Patients with Rheumatoid Arthritis Treated with Long-Term Upadacitinib Therapy in Five Randomized Controlled Trials. Rheumatol Ther. 2022 Dec;9(6):1517-1529. doi: 10.1007/s40744-022-00483-4. Epub 2022 Sep 20.
Mysler E, Tanaka Y, Kavanaugh A, Aletaha D, Taylor PC, Song IH, Shaw T, Song Y, DeMasi R, Ali M, Fleischmann R. Impact of initial therapy with upadacitinib or adalimumab on achievement of 48-week treatment goals in patients with rheumatoid arthritis: post hoc analysis of SELECT-COMPARE. Rheumatology (Oxford). 2023 May 2;62(5):1804-1813. doi: 10.1093/rheumatology/keac477.
Peterfy CG, Strand V, Friedman A, Hall S, Mysler E, Durez P, Baraliakos X, Enejosa JV, Shaw T, Li Y, Chen S, Song IH. Inhibition of structural joint damage progression with upadacitinib in rheumatoid arthritis: 1-year outcomes from the SELECT phase 3 program. Rheumatology (Oxford). 2022 Aug 3;61(8):3246-3256. doi: 10.1093/rheumatology/keab861.
Yamaoka K, Tanaka Y, Kameda H, Khan N, Sasaki N, Harigai M, Song Y, Zhang Y, Takeuchi T. The Safety Profile of Upadacitinib in Patients with Rheumatoid Arthritis in Japan. Drug Saf. 2021 Jun;44(6):711-722. doi: 10.1007/s40264-021-01067-x. Epub 2021 May 27.
Strand V, Tundia N, Bergman M, Ostor A, Durez P, Song IH, Enejosa J, Schlacher C, Song Y, Fleischmann R. Upadacitinib improves patient-reported outcomes vs placebo or adalimumab in patients with rheumatoid arthritis: results from SELECT-COMPARE. Rheumatology (Oxford). 2021 Dec 1;60(12):5583-5594. doi: 10.1093/rheumatology/keab158.
Fleischmann RM, Blanco R, Hall S, Thomson GTD, Van den Bosch FE, Zerbini C, Bessette L, Enejosa J, Li Y, Song Y, DeMasi R, Song IH. Switching between Janus kinase inhibitor upadacitinib and adalimumab following insufficient response: efficacy and safety in patients with rheumatoid arthritis. Ann Rheum Dis. 2021 Apr;80(4):432-439. doi: 10.1136/annrheumdis-2020-218412. Epub 2020 Nov 4.
Cohen SB, van Vollenhoven RF, Winthrop KL, Zerbini CAF, Tanaka Y, Bessette L, Zhang Y, Khan N, Hendrickson B, Enejosa JV, Burmester GR. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis. 2021 Mar;80(3):304-311. doi: 10.1136/annrheumdis-2020-218510. Epub 2020 Oct 28.
Nader A, Mohamed MF, Winzenborg I, Doelger E, Noertersheuser P, Pangan AL, Othman AA. Exposure-Response Analyses of Upadacitinib Efficacy and Safety in Phase II and III Studies to Support Benefit-Risk Assessment in Rheumatoid Arthritis. Clin Pharmacol Ther. 2020 Apr;107(4):994-1003. doi: 10.1002/cpt.1671. Epub 2019 Nov 30.
Fleischmann RM, Genovese MC, Enejosa JV, Mysler E, Bessette L, Peterfy C, Durez P, Ostor A, Li Y, Song IH. Safety and effectiveness of upadacitinib or adalimumab plus methotrexate in patients with rheumatoid arthritis over 48 weeks with switch to alternate therapy in patients with insufficient response. Ann Rheum Dis. 2019 Nov;78(11):1454-1462. doi: 10.1136/annrheumdis-2019-215764. Epub 2019 Jul 30.
FG001
Adalimumab
Participants randomized to receive placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD. At Week 26 remaining participants who did not achieve low disease activity (defined as Clinical Disease Activity Index [CDAI] ≤ 10) were switched to 15 mg upadacitinib orally QD.
FG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow. At Week 26 remaining participants who did not achieve low disease activity (defined as CDAI ≤ 10) were switched to 40 mg adalimumab eow.
FG000651 subjects
FG001327 subjects
FG002651 subjects
Received Assigned Study Drug
FG000651 subjects
FG001327 subjects
FG002650 subjectsOne participant received a placebo injection but no oral study drug before discontinuing the study
Completed Week 14 on Study Drug
FG000620 subjects
FG001300 subjects
FG002620 subjects
Rescued at Week 14
FG000231 subjects
FG00156 subjects
FG00278 subjects
Rescued at Week 18
FG00048 subjectsOne participant rescued at week 18 did not receive any dose of upadacitinib
FG00114 subjects
FG00229 subjects
Rescued at Week 22
FG00026 subjects
FG0017 subjects
FG00218 subjects
COMPLETED
Participants who completed Week 26
FG000595 subjects
FG001288 subjects
FG002600 subjects
NOT COMPLETED
FG00056 subjects
FG00139 subjects
FG00251 subjects
Type
Comment
Reasons
Adverse Event
FG00017 subjects
FG00120 subjects
FG00222 subjects
Withdrawal by Subject
FG00022 subjects
FG00111 subjects
FG00215 subjects
Lost to Follow-up
FG0007 subjects
FG0014 subjects
FG0025 subjects
Lack of Efficacy
FG0004 subjects
FG0010 subjects
FG0021 subjects
Other
FG0006 subjects
FG0014 subjects
FG0028 subjects
The full analysis set consisted of all randomized participants who received at least 1 dose of study drug (placebo, adalimumab, or upadacitinib).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
BG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
BG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000651
BG001327
BG002651
BG0031629
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002651
ParticipantsBG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Geographic Region
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Duration of Rheumatoid Arthritis Diagnosis
Mean
Standard Deviation
years
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Tender Joint Count
A total of 68 joints were assessed for the presence or absence of tenderness.
Mean
Standard Deviation
tender joints
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Swollen Joint Count
A total of 66 joints were assessed for the presence or absence of swelling.
Mean
Standard Deviation
swollen joints
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Patient's Assessment of Pain
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100 mm. A score of 0 mm indicates "no pain" and a score of 100 mm indicates "worst possible pain."
Participants with available data
Mean
Standard Deviation
mm
Title
Denominators
Categories
ParticipantsBG000649
ParticipantsBG001325
ParticipantsBG002
Patient's Global Assessment of Disease Activity
The participant was asked to rate their current RA disease activity over the past 24 hours on a 100 mm VAS, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.
Participants with available data
Mean
Standard Deviation
mm
Title
Denominators
Categories
ParticipantsBG000649
ParticipantsBG001324
ParticipantsBG002
Physician's Global Assessment of Disease Activity
The physician rated the participant's current global RA disease activity (independently from the participant's assessment) on a VAS scale from 0 to 100 mm, where 0 mm indicates very low disease activity and 100 mm indicates very high disease activity.
Participants with available data
Mean
Standard Deviation
mm
Title
Denominators
Categories
ParticipantsBG000620
ParticipantsBG001305
ParticipantsBG002
Health Assessment Questionnaire - Disability Index (HAQ-DI)
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.
Participants with available data
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
ParticipantsBG000649
ParticipantsBG001
High-sensitivity C-reactive Protein (hsCRP)
Mean
Standard Deviation
mg/L
Title
Denominators
Categories
ParticipantsBG000651
ParticipantsBG001327
ParticipantsBG002
Disease Activity Score 28 Based on CRP (DAS28[CRP])
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 > 5.1 indicates high disease activity, a DAS28 score ≤ 3.2 indicates low disease activity, and a DAS28 score < 2.6 indicates clinical remission.
Participants with available data
Mean
Standard Deviation
units on a scale
Title
Denominators
Categories
ParticipantsBG000649
ParticipantsBG001
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:
≥ 20% improvement in 68-tender joint count;
≥ 20% improvement in 66-swollen joint count; and
≥ 20% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
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.
Posted
Number
95% Confidence Interval
percentage of participants
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000651
OG001327
OG002651
Title
Denominators
Categories
Title
Measurements
OG00036.4(32.7 to 40.1)
OG00163.0(57.8 to 68.2)
OG00270.5(67.0 to 74.0)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was the primary analysis for US/FDA regulatory purposes, and a ranked key secondary endpoint for EU/EMA regulatory purposes.
Response Rate Difference
34.1
2-Sided
95
29.0
39.2
Response Rate Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
Primary
Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 12.
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28 score less than 2.6 indicates clinical remission.
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.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Secondary
Change From Baseline in DAS28 (CRP) at Week 12
The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Full analysis set participants with available data at Baseline; multiple imputation was used for missing post-baseline data.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Secondary
Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.
Full analysis set participants with available data at Baseline; linear extrapolation was used for participants who discontinued prior to Week 26 or who were rescued prior to Week 26.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline and Week 26
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
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.
Full analysis set participants with available data at baseline; multiple imputation was used for missing data.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
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:
≥ 50% improvement in 68-tender joint count;
≥ 50% improvement in 66-swollen joint count; and
≥ 50% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
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.
Posted
Number
95% Confidence Interval
percentage of participants
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
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.
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.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Secondary
Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.
A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.
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.
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Secondary
Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.
CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom CDAI data were missing at Week 12 were considered non-responders
Posted
Number
95% Confidence Interval
percentage of participants
Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Secondary
Change From Baseline in Duration of Morning Stiffness at Week 12
Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
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.
Posted
Least Squares Mean
95% Confidence Interval
minutes
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Upadacitinib
Secondary
Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
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.
Posted
Least Squares Mean
95% Confidence Interval
units on a scale
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Secondary
Change From Baseline in Patient's Assessment of Pain at Week 12
Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
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.
Posted
Least Squares Mean
95% Confidence Interval
mm
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Secondary
Percentage of Participants With No Radiographic Progression at Week 26
No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst).
Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).
Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).
Full analysis set participants with available data at Baseline; linear extrapolation was used for participants who discontinued prior to Week 26 or who were rescued prior to Week 26.
Posted
Number
95% Confidence Interval
percentage of participants
Baseline and Week 26
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
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:
≥ 70% improvement in 68-tender joint count;
≥ 70% improvement in 66-swollen joint count; and
≥ 70% improvement in at least 3 of the 5 following parameters:
Physician global assessment of disease activity
Patient global assessment of disease activity
Patient assessment of pain
Health Assessment Questionnaire - Disability Index (HAQ-DI)
High-sensitivity C-reactive protein (hsCRP).
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.
Posted
Number
95% Confidence Interval
percentage of participants
Baseline and Week 12
ID
Title
Description
OG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in tender joint count (TJC) and swollen joint count (SJC) at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Time Frame
From first dose of study drug up to Week 26, or up to 30 days after last dose for those receiving placebo or upadacitinib who discontinued prior to Week 26, or up to 70 days after last dose for those receiving adalimumab who discontinued prior to Week 26.
Description
One participant randomized to upadacitinib received placebo to adalimumab but did not receive upadacitinib and is counted in the placebo group for analyses of safety.
One participant who switched from placebo to upadacitinib at Week 18 did not receive any upadacitinib and is therefore not counted in the placebo / upadacitinib treatment group.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Placebo
Participants received placebo to upadacitinib orally once daily (QD) and placebo to adalimumab by subcutaneous injection once every two weeks (eow) for up to 26 weeks. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Includes events up to the time of rescue (at Weeks 14, 18, 22) or up to Week 26 for those who were not rescued.
2
652
19
652
43
652
EG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
Includes events up to the time of rescue (at Weeks 14, 18, 22) or up to Week 26 for those who were not rescued.
2
327
14
327
16
327
EG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Includes events up to the time of rescue (at Weeks 14, 18, 22) or up to Week 26 for those who were not rescued.
0
650
24
650
72
650
EG003
Placebo / Upadacitinib
Participants who originally received placebo were switched at Weeks 14, 18, or 22 to receive 15 mg upadacitinib orally QD.
Includes all events that occurred after the switch to rescue treatment up to Week 26.
0
304
7
304
9
304
EG004
Adalimumab / Upadacitinib
Participants who originally received adalimumab were switched at Weeks 14, 18, or 22 to receive 15 mg upadacitinib orally QD.
Includes all events that occurred after the switch to rescue treatment up to Week 26.
0
77
0
77
6
77
EG005
Upadacitinib / Adalimumab
Participants who originally received 15 mg upadacitinib QD were switched at Weeks 14, 18, or 22 to receive 40 mg adalimumab eow.
Includes all events that occurred after the switch to rescue treatment up to Week 26.
0
125
2
125
4
125
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
ACUTE MYOCARDIAL INFARCTION
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG0031 events1 affected304 at risk
EG0040 events0 affected77 at risk
EG0050 events0 affected125 at risk
ATRIAL FLUTTER
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CARDIAC FAILURE
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CARDIOGENIC SHOCK
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
LEFT VENTRICULAR FAILURE
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
MYOCARDIAL INFARCTION
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
RIGHT VENTRICULAR DILATATION
Cardiac disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CATARACT
Eye disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
DIARRHOEA
Gastrointestinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0022 events1 affected650 at risk
EG003
FOOD POISONING
Gastrointestinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
GASTRIC POLYPS
Gastrointestinal disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
PYREXIA
General disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
SUDDEN DEATH
General disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CHOLELITHIASIS
Hepatobiliary disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
HEPATITIS TOXIC
Hepatobiliary disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
APPENDICITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0022 events2 affected650 at risk
EG003
BRONCHIOLITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
BRONCHITIS BACTERIAL
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CELLULITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0012 events2 affected327 at risk
EG0020 events0 affected650 at risk
EG003
FALLOPIAN TUBE ABSCESS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
GASTROENTERITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0003 events3 affected652 at risk
EG0010 events0 affected327 at risk
EG0022 events2 affected650 at risk
EG003
INFECTED BITE
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
INFECTIOUS COLITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
INFLUENZA
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
KIDNEY INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
LOWER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
LUNG INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
PERITONITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
PNEUMOCYSTIS JIROVECII PNEUMONIA
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0002 events2 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
PNEUMONIA
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
PYELONEPHRITIS ACUTE
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
SEPSIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
SOFT TISSUE INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
UROSEPSIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0021 events1 affected650 at risk
EG003
VIRAL INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
AIRWAY COMPLICATION OF ANAESTHESIA
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
CRANIOCEREBRAL INJURY
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
FALL
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
FIBULA FRACTURE
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
HEAD INJURY
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
HIP FRACTURE
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
SPINAL COMPRESSION FRACTURE
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
TIBIA FRACTURE
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
TOXICITY TO VARIOUS AGENTS
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
UPPER LIMB FRACTURE
Injury, poisoning and procedural complications
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
ARTHRITIS
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
LUMBAR SPINAL STENOSIS
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
NECK PAIN
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
OSTEOARTHRITIS
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
RHEUMATOID ARTHRITIS
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
VERTEBRAL LESION
Musculoskeletal and connective tissue disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
BASAL CELL CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
CERVIX CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
DEMYELINATION
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
DIZZINESS
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
NEUROTOXICITY
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
PARAPLEGIA
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
SEIZURE
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
SPINAL CORD HAEMORRHAGE
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
SYNCOPE
Nervous system disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
ABORTION SPONTANEOUS
Pregnancy, puerperium and perinatal conditions
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0022 events2 affected650 at risk
EG003
CONFUSIONAL STATE
Psychiatric disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
BLADDER PROLAPSE
Renal and urinary disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
RENAL FAILURE
Renal and urinary disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
ENDOMETRIAL HYPERPLASIA
Reproductive system and breast disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
MENORRHAGIA
Reproductive system and breast disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
OVARIAN CYST RUPTURED
Reproductive system and breast disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
VAGINAL HAEMORRHAGE
Reproductive system and breast disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
ASTHMA
Respiratory, thoracic and mediastinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
BRONCHOSPASM
Respiratory, thoracic and mediastinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0021 events1 affected650 at risk
EG003
IDIOPATHIC PULMONARY FIBROSIS
Respiratory, thoracic and mediastinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
PULMONARY EMBOLISM
Respiratory, thoracic and mediastinal disorders
MedDRA (19.0)
Systematic Assessment
EG0001 events1 affected652 at risk
EG0013 events3 affected327 at risk
EG0021 events1 affected650 at risk
EG003
PULMONARY FIBROSIS
Respiratory, thoracic and mediastinal disorders
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0011 events1 affected327 at risk
EG0020 events0 affected650 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
NASOPHARYNGITIS
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG00020 events19 affected652 at risk
EG00110 events9 affected327 at risk
EG00242 events36 affected650 at risk
EG0030 events0 affected304 at risk
EG0040 events0 affected77 at risk
EG0050 events0 affected125 at risk
UPPER RESPIRATORY TRACT INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG00024 events24 affected652 at risk
EG0018 events7 affected327 at risk
EG00243 events37 affected650 at risk
EG003
URINARY TRACT INFECTION
Infections and infestations
MedDRA (19.0)
Systematic Assessment
EG0000 events0 affected652 at risk
EG0010 events0 affected327 at risk
EG0020 events0 affected650 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000651
OG001327
OG002651
Title
Denominators
Categories
Title
Measurements
OG0006.1(4.3 to 8.0)
OG00118.0(13.9 to 22.2)
OG00228.7(25.2 to 32.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was the primary analysis for EU/EMA regulatory purposes, and a ranked key secondary endpoint for US/FDA regulatory purposes.
Response Rate Difference
22.6
2-Sided
95
18.6
26.5
Response Rate Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000643
OG001319
OG002634
Title
Denominators
Categories
Title
Measurements
OG000-1.15(-1.276 to -1.017)
OG001-2.01(-2.175 to -1.848)
OG002-2.48(-2.608 to -2.347)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
ANCOVA
Analysis of covariance (ANCOVA) model with treatment, prior biological DMARD use, and Baseline value as covariates.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
-1.33
2-Sided
95
-1.469
-1.194
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
ANCOVA
ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
-0.47
2-Sided
95
-0.638
-0.295
Treatment Difference = Upadacitinib - Adalimumab
Superiority
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000599
OG001296
OG002593
Title
Denominators
Categories
Title
Measurements
OG0000.92(0.64 to 1.20)
OG0010.10(-0.25 to 0.46)
OG0020.24(-0.04 to 0.53)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
ANCOVA
ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
-0.67
2-Sided
95
-0.97
-0.37
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
ANCOVA
ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
0.448
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
0.14
2-Sided
95
-0.23
0.51
Treatment Difference = Upadacitinib - Adalimumab
Superiority
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000648
OG001324
OG002644
Title
Denominators
Categories
Title
Measurements
OG000-0.28(-0.339 to -0.227)
OG001-0.49(-0.556 to -0.415)
OG002-0.60(-0.653 to -0.538)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
ANCOVA
ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
-0.31
2-Sided
95
-0.372
-0.253
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
ANCOVA
ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
0.004
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
LS Mean Difference
-0.11
2-Sided
95
-0.184
-0.036
Treatment Difference = Upadacitinib - Adalimumab
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
A non-inferiority test of upadacitinib versus adalimumab was evaluated using the lower bound of the 95% confidence interval (CI) of the treatment difference against a non-inferiority margin of 10%. This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
Response Rate Difference
30.3
2-Sided
95
25.6
35.0
Response Rate Difference = Upadacitinib - Placebo
Superiority
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000616
OG001309
OG002616
Title
Denominators
Categories
Title
Measurements
OG0003.56(2.79 to 4.33)
OG0016.27(5.31 to 7.23)
OG0027.89(7.11 to 8.68)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
4.33
2-Sided
95
3.52
5.15
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
0.002
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
1.62
2-Sided
95
0.62
2.62
Treatment Difference = Upadacitinib - Adalimumab
Superiority
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000651
OG001327
OG002651
Title
Denominators
Categories
Title
Measurements
OG00013.8(11.2 to 16.5)
OG00128.7(23.8 to 33.7)
OG00245.0(41.2 to 48.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Response Rate Difference
31.2
2-Sided
95
26.5
35.8
Response Rate Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
A non-inferiority test of upadacitinib versus adalimumab was evaluated using the lower bound of the 95% confidence interval (CI) of the treatment difference against a non-inferiority margin of 10%. This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for EU/EMA only.
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
Superiority
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000651
OG001327
OG002651
Title
Denominators
Categories
Title
Measurements
OG00016.3(13.4 to 19.1)
OG00130.0(25.0 to 34.9)
OG00240.4(36.6 to 44.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Response Rate Difference
24.1
2-Sided
95
19.4
28.8
Response Rate Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000619
OG001306
OG002618
Title
Denominators
Categories
Title
Measurements
OG000-48.59(-58.84 to -38.34)
OG001-82.71(-95.80 to -69.62)
OG002-92.63(-103.03 to -82.23)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
-44.04
2-Sided
95
-55.39
-32.69
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
0.164
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
-9.92
2-Sided
95
-23.89
4.05
Treatment Difference = Upadacitinib - Adalimumab
Superiority
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000613
OG001307
OG002612
Title
Denominators
Categories
Title
Measurements
OG0004.81(3.85 to 5.77)
OG0017.44(6.25 to 8.64)
OG0028.95(7.98 to 9.93)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
LS Mean Difference
4.15
2-Sided
95
3.13
5.16
Treatment Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
0.017
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
1.51
2-Sided
95
0.27
2.76
Treatment Difference = Upadacitinib - Adalimumab
Superiority
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000616
OG001307
OG002614
Title
Denominators
Categories
Title
Measurements
OG000-15.46(-17.63 to -13.29)
OG001-25.31(-28.16 to -22.47)
OG002-31.76(-33.96 to -29.56)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG001
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
LS Mean Difference
-6.45
2-Sided
95
-9.63
-3.27
Treatment Difference = Upadacitinib - Adalimumab
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG000
OG002
Mixed Effect Model Repeat Measurement
MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
LS Mean Difference
-16.30
2-Sided
95
-18.89
-13.71
Treatment Difference = Upadacitinib - Placebo
Superiority
OG001
Adalimumab
Participants received placebo to upadacitinib orally QD and 40 mg adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 15 mg upadacitinib orally QD.
OG002
Upadacitinib
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000599
OG001296
OG002593
Title
Denominators
Categories
Title
Measurements
OG00076.0(72.5 to 79.4)
OG00186.8(83.0 to 90.7)
OG00283.5(80.5 to 86.5)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for EU/EMA only.
Response Rate Difference
7.5
2-Sided
95
3.0
12.1
Response Rate Difference = Upadacitinib - Placebo
Superiority
In order to preserve Type I error, a step-down approach was used to test the primary and ranked key secondary endpoints in a pre-specified order where statistical significance at the 0.05 level could be claimed for a lower ranked endpoint only if the previous endpoint in the sequence met the requirements of significance.
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
0.187
This comparison was not part of the pre-specified multiplicity testing sequence.
Participants randomized to receive 15 mg upadacitinib orally QD and placebo to adalimumab by subcutaneous injection eow for up to 48 weeks in Period 1. Participants who did not achieve a ≥ 20% improvement in TJC and SJC at Weeks 14, 18, or 22 compared to Baseline were switched to 40 mg adalimumab eow.
Units
Counts
Participants
OG000651
OG001327
OG002651
Title
Denominators
Categories
Title
Measurements
OG0004.9(3.3 to 6.6)
OG00113.5(9.8 to 17.2)
OG00224.9(21.6 to 28.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.
Response Rate Difference
20.0
2-Sided
95
16.3
23.7
Response Rate Difference = Upadacitinib - Placebo
Superiority
OG001
OG002
Cochran-Mantel-Haenszel
Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
<0.001
This comparison was not part of the pre-specified multiplicity testing sequence.