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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 (SELECT-COMPARE)

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ClinicalTrials.gov Identifier: NCT02629159
Recruitment Status : Active, not recruiting
First Posted : December 14, 2015
Results First Posted : October 7, 2019
Last Update Posted : October 7, 2019
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Drug: Placebo for Adalimumab
Drug: Adalimumab
Drug: Placebo for Upadacitinib
Drug: Upadacitinib
Enrollment 1629
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.

Pre-assignment Details

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.

Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 651 327 651
Received Assigned Study Drug 651 327 650 [1]
Completed Week 14 on Study Drug 620 300 620
Rescued at Week 14 231 56 78
Rescued at Week 18 48 [2] 14 29
Rescued at Week 22 26 7 18
Completed [3] 595 288 600
Not Completed 56 39 51
Reason Not Completed
Adverse Event             17             20             22
Withdrawal by Subject             22             11             15
Lost to Follow-up             7             4             5
Lack of Efficacy             4             0             1
Other             6             4             8
[1]
One participant received a placebo injection but no oral study drug before discontinuing the study
[2]
One participant rescued at week 18 did not receive any dose of upadacitinib
[3]
Participants who completed Week 26
Arm/Group Title Placebo Adalimumab Upadacitinib Total
Hide Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 651 327 651 1629
Hide Baseline Analysis Population Description
The full analysis set consisted of all randomized participants who received at least 1 dose of study drug (placebo, adalimumab, or upadacitinib).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
53.6  (12.24) 53.7  (11.70) 54.2  (12.08) 53.9  (12.07)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
< 40 years
91
  14.0%
39
  11.9%
81
  12.4%
211
  13.0%
40 to 64 years
437
  67.1%
232
  70.9%
439
  67.4%
1108
  68.0%
≥ 65 years
123
  18.9%
56
  17.1%
131
  20.1%
310
  19.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
Female
512
  78.6%
259
  79.2%
521
  80.0%
1292
  79.3%
Male
139
  21.4%
68
  20.8%
130
  20.0%
337
  20.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
Hispanic or Latino
206
  31.6%
106
  32.4%
215
  33.0%
527
  32.4%
Not Hispanic or Latino
445
  68.4%
221
  67.6%
436
  67.0%
1102
  67.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
White
561
  86.2%
292
  89.3%
576
  88.5%
1429
  87.7%
Black or African American
38
   5.8%
17
   5.2%
33
   5.1%
88
   5.4%
American Indian/Alaska Native
2
   0.3%
1
   0.3%
1
   0.2%
4
   0.2%
Native Hawaiian or other Pacific Islander
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.1%
Asian
39
   6.0%
15
   4.6%
31
   4.8%
85
   5.2%
Multiple
10
   1.5%
2
   0.6%
10
   1.5%
22
   1.4%
Geographic Region  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
North America
121
  18.6%
60
  18.3%
122
  18.7%
303
  18.6%
South/Central America
173
  26.6%
86
  26.3%
173
  26.6%
432
  26.5%
Western Europe
35
   5.4%
19
   5.8%
35
   5.4%
89
   5.5%
Eastern Europe
262
  40.2%
132
  40.4%
262
  40.2%
656
  40.3%
Asia
21
   3.2%
10
   3.1%
21
   3.2%
52
   3.2%
Other
39
   6.0%
20
   6.1%
38
   5.8%
97
   6.0%
Duration of Rheumatoid Arthritis Diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
8.3  (8.00) 8.3  (8.41) 8.1  (7.73) 8.2  (7.97)
Tender Joint Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Tender joints
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
26.0  (14.30) 26.4  (15.16) 26.4  (15.15) 26.2  (14.81)
[1]
Measure Description: A total of 68 joints were assessed for the presence or absence of tenderness.
Swollen Joint Count   [1] 
Mean (Standard Deviation)
Unit of measure:  Swollen joints
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
16.2  (8.97) 16.3  (9.19) 16.6  (10.31) 16.4  (9.57)
[1]
Measure Description: A total of 66 joints were assessed for the presence or absence of swelling.
Patient's Assessment of Pain   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 649 participants 325 participants 647 participants 1621 participants
65.0  (20.67) 66.2  (20.51) 65.7  (21.02) 65.5  (20.77)
[1]
Measure Description: 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."
[2]
Measure Analysis Population Description: Participants with available data
Patient's Global Assessment of Disease Activity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 649 participants 324 participants 647 participants 1620 participants
63.8  (21.49) 65.8  (21.08) 64.3  (21.83) 64.4  (21.55)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: Participants with available data
Physician's Global Assessment of Disease Activity   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Mm
Number Analyzed 620 participants 305 participants 616 participants 1541 participants
66.0  (18.17) 65.1  (17.60) 65.6  (17.06) 65.7  (17.62)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: Participants with available data
Health Assessment Questionnaire - Disability Index (HAQ-DI)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 649 participants 325 participants 646 participants 1620 participants
1.6  (0.61) 1.6  (0.59) 1.6  (0.64) 1.6  (0.62)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: Participants with available data
High-sensitivity C-reactive Protein (hsCRP)  
Mean (Standard Deviation)
Unit of measure:  mg/L
Number Analyzed 651 participants 327 participants 651 participants 1629 participants
18.0  (21.52) 19.8  (21.51) 17.9  (22.49) 18.3  (21.91)
Disease Activity Score 28 Based on CRP (DAS28[CRP])   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 649 participants 324 participants 647 participants 1620 participants
5.8  (0.94) 5.9  (0.96) 5.8  (0.97) 5.8  (0.96)
[1]
Measure Description: 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.
[2]
Measure Analysis Population Description: Participants with available data
1.Primary Outcome
Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
Hide Description

The primary endpoint for United States (US)/Food and Drug Administration (FDA) regulatory purposes was ACR 20% response (ACR20) at Week 12. Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR20 response criteria:

  1. ≥ 20% improvement in 68-tender joint count;
  2. ≥ 20% improvement in 66-swollen joint count; and
  3. ≥ 20% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
36.4
(32.7 to 40.1)
63.0
(57.8 to 68.2)
70.5
(67.0 to 74.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was the primary analysis for US/FDA regulatory purposes, and a ranked key secondary endpoint for EU/EMA regulatory purposes.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 34.1
Confidence Interval (2-Sided) 95%
29.0 to 39.2
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
1.2 to 13.8
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
2.Primary Outcome
Title Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
Hide Description

The primary endpoint for European Union (EU)/European Medicines Agency (EMA) regulatory purposes was clinical remission, based on a Disease Activity Score 28 (DAS28)-CRP score of < 2.6 at Week 12.

The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

A DAS28 score less than 2.6 indicates clinical remission.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom DAS28 data were missing at Week 12 were considered non-responders.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.1
(4.3 to 8.0)
18.0
(13.9 to 22.2)
28.7
(25.2 to 32.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was the primary analysis for EU/EMA regulatory purposes, and a ranked key secondary endpoint for US/FDA regulatory purposes.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 22.6
Confidence Interval (2-Sided) 95%
18.6 to 26.5
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 10.7
Confidence Interval (2-Sided) 95%
5.3 to 16.1
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
3.Secondary Outcome
Title Change From Baseline in DAS28 (CRP) at Week 12
Hide Description The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data at Baseline; multiple imputation was used for missing post-baseline data.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 643 319 634
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-1.15
(-1.276 to -1.017)
-2.01
(-2.175 to -1.848)
-2.48
(-2.608 to -2.347)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method ANCOVA
Comments Analysis of covariance (ANCOVA) model with treatment, prior biological DMARD use, and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-1.469 to -1.194
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method ANCOVA
Comments ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.47
Confidence Interval (2-Sided) 95%
-0.638 to -0.295
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
4.Secondary Outcome
Title Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
Hide Description

The mTSS measures the level of joint damage from radiographs of the hands and feet, assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score.

Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).

JSN was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).

The mTSS is the sum of the joint erosion and JSN scores and ranges from 0 (normal) to 448 (worst). A negative change from Baseline in mTSS indicates improvement in joint damage whereas a change from Baseline greater than 0 indicates progression.

Time Frame Baseline and Week 26
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 599 296 593
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
0.92
(0.64 to 1.20)
0.10
(-0.25 to 0.46)
0.24
(-0.04 to 0.53)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method ANCOVA
Comments ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.67
Confidence Interval (2-Sided) 95%
-0.97 to -0.37
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.448
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method ANCOVA
Comments ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.23 to 0.51
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
5.Secondary Outcome
Title Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
Hide Description

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

A negative change from Baseline in the overall score indicates improvement.

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data at baseline; multiple imputation was used for missing data.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 648 324 644
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
-0.28
(-0.339 to -0.227)
-0.49
(-0.556 to -0.415)
-0.60
(-0.653 to -0.538)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method ANCOVA
Comments ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.31
Confidence Interval (2-Sided) 95%
-0.372 to -0.253
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value 0.004
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
Method ANCOVA
Comments ANCOVA model with treatment, prior biological DMARD use and Baseline value as covariates.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.184 to -0.036
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
6.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Hide Description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR50 response criteria:

  1. ≥ 50% improvement in 68-tender joint count;
  2. ≥ 50% improvement in 66-swollen joint count; and
  3. ≥ 50% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.9
(12.2 to 17.6)
29.1
(24.1 to 34.0)
45.2
(41.3 to 49.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments 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.
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 16.1
Confidence Interval (2-Sided) 95%
9.9 to 22.3
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 30.3
Confidence Interval (2-Sided) 95%
25.6 to 35.0
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
7.Secondary Outcome
Title Change From Baseline in Short-Form 36 (SF-36) Physical Component Score (PCS) at Week 12
Hide Description

The Short Form 36-Item Health Survey (SF-36) Version 2 is a self-administered questionnaire that measures the impact of disease on overall quality of life during the past 4 weeks. The SF-36 consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health).

The physical component score is a weighted combination of the 8 subscales with positive weighting for physical functioning, role-physical, bodily pain, and general health. The PCS was calculated using norm-based scoring so that 50 is the average score and the standard deviation equals 10. Higher scores are associated with better functioning/quality of life; a positive change from baseline score indicates an improvement.

Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 616 309 616
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
3.56
(2.79 to 4.33)
6.27
(5.31 to 7.23)
7.89
(7.11 to 8.68)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.33
Confidence Interval (2-Sided) 95%
3.52 to 5.15
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.62
Confidence Interval (2-Sided) 95%
0.62 to 2.62
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
8.Secondary Outcome
Title Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
Hide Description

The DAS28(CRP) is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to approximately 10, where higher scores indicate more disease activity.

A DAS28(CRP) score less than or equal to 3.2 indicates low disease activity.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom DAS28 data were missing at Week 12 were considered non-responders.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
13.8
(11.2 to 16.5)
28.7
(23.8 to 33.7)
45.0
(41.2 to 48.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 31.2
Confidence Interval (2-Sided) 95%
26.5 to 35.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments 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.
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
10.0 to 22.5
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
9.Secondary Outcome
Title Percentage of Participants Achieving Low Disease Activity Based on CDAI at Week 12
Hide Description

Low disease activity based on the clinical disease activity index (CDAI) is defined as a CDAI score ≤ 10.

CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity.

Time Frame Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
16.3
(13.4 to 19.1)
30.0
(25.0 to 34.9)
40.4
(36.6 to 44.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 24.1
Confidence Interval (2-Sided) 95%
19.4 to 28.8
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
4.2 to 16.7
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
10.Secondary Outcome
Title Change From Baseline in Duration of Morning Stiffness at Week 12
Hide Description Participants were asked to indicate the time it took for them to get as limber as possible after awakening with morning stiffness over the past 7 days. A negative change from Baseline indicates improvement.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 619 306 618
Least Squares Mean (95% Confidence Interval)
Unit of Measure: minutes
-48.59
(-58.84 to -38.34)
-82.71
(-95.80 to -69.62)
-92.63
(-103.03 to -82.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -44.04
Confidence Interval (2-Sided) 95%
-55.39 to -32.69
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.164
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -9.92
Confidence Interval (2-Sided) 95%
-23.89 to 4.05
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
11.Secondary Outcome
Title Change From Baseline in in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F)
Hide Description The FACIT Fatigue scale is a 13-item tool that measures an individual's level of fatigue during their usual daily activities over the past 7 days. Each of the fatigue and impact of fatigue items are measured on a four point Likert scale. The FACIT Fatigue Scale is the sum of the individual 13 scores and ranges from 0 to 52 where higher scores indicate better the quality of life. A positive change from Baseline indicates improvement.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 613 307 612
Least Squares Mean (95% Confidence Interval)
Unit of Measure: units on a scale
4.81
(3.85 to 5.77)
7.44
(6.25 to 8.64)
8.95
(7.98 to 9.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA and EU/EMA.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 4.15
Confidence Interval (2-Sided) 95%
3.13 to 5.16
Estimation Comments Treatment Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
0.27 to 2.76
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
12.Secondary Outcome
Title Change From Baseline in Patient's Assessment of Pain at Week 12
Hide Description Participants were asked to indicate the severity of their arthritis pain within the previous week on a visual analog scale (VAS) from 0 to 100. A score of 0 indicates "no pain" and a score of 100 indicates "worst possible pain." A negative change from Baseline indicates improvement.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set participants with available data; a mixed effect model repeat measurement (MMRM) analysis with data from observed cases to Week 12 was used.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 616 307 614
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mm
-15.46
(-17.63 to -13.29)
-25.31
(-28.16 to -22.47)
-31.76
(-33.96 to -29.56)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for US/FDA only.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -6.45
Confidence Interval (2-Sided) 95%
-9.63 to -3.27
Estimation Comments Treatment Difference = Upadacitinib - Adalimumab
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Mixed Effect Model Repeat Measurement
Comments MMRM model with fixed effects of treatment, visit, and treatment-by-visit interaction, previous bDMARD use, and Baseline value as covariate.
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -16.30
Confidence Interval (2-Sided) 95%
-18.89 to -13.71
Estimation Comments Treatment Difference = Upadacitinib - Placebo
13.Secondary Outcome
Title Percentage of Participants With No Radiographic Progression at Week 26
Hide Description

No radiographic progression is defined as a change from Baseline in mTSS ≤ 0. The mTSS measures the level of joint damage from radiographs of the hands and feet, which were assessed by 2 independent, blinded readers. mTSS is calculated as the sum of the total joint erosion score and total joint space narrowing (JSN) score and ranges from 0 (normal) to 448 (worst).

Joint erosion severity was assessed in 16 joints in each hand and wrist and 6 joints in each foot. Each joint was scored from 0 (no erosion) to 5 for hands/wrists or to 10 for feet (complete collapse). The total erosion score ranges from 0 to 280 (worst).

Joint space narrowing (JSN) was assessed in 15 joints of each hand and wrist, and 6 joints of each foot, including subluxation, from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation). The total JSN score ranges from 0 to 168 (worst).

Time Frame Baseline and Week 26
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Hide Analysis Population Description
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.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 599 296 593
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
76.0
(72.5 to 79.4)
86.8
(83.0 to 90.7)
83.5
(80.5 to 86.5)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments 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.
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was a ranked key secondary endpoint in the pre-specified multiplicity testing sequence for EU/EMA only.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
3.0 to 12.1
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.187
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use.
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-8.2 to 1.5
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
14.Secondary Outcome
Title Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Hide Description

Participants who met the following 3 conditions for improvement from baseline were classified as meeting the ACR70 response criteria:

  1. ≥ 70% improvement in 68-tender joint count;
  2. ≥ 70% improvement in 66-swollen joint count; and
  3. ≥ 70% improvement in at least 3 of the 5 following parameters:

    • Physician global assessment of disease activity
    • Patient global assessment of disease activity
    • Patient assessment of pain
    • Health Assessment Questionnaire - Disability Index (HAQ-DI)
    • High-sensitivity C-reactive protein (hsCRP).
Time Frame Baseline and Week 12
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Hide Analysis Population Description
Full analysis set; participants who prematurely discontinued from study drug prior to Week 12 or for whom ACR data were missing at Week 12 were considered non-responders.
Arm/Group Title Placebo Adalimumab Upadacitinib
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 651 327 651
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
4.9
(3.3 to 6.6)
13.5
(9.8 to 17.2)
24.9
(21.6 to 28.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 20.0
Confidence Interval (2-Sided) 95%
16.3 to 23.7
Estimation Comments Response Rate Difference = Upadacitinib - Placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Adalimumab, Upadacitinib
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments This comparison was not part of the pre-specified multiplicity testing sequence.
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel test adjusted for the stratification factor of prior biological DMARD use
Method of Estimation Estimation Parameter Response Rate Difference
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
6.5 to 16.4
Estimation Comments Response Rate Difference = Upadacitinib - Adalimumab
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.
Adverse Event Reporting 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.

 
Arm/Group Title Placebo Adalimumab Upadacitinib Placebo / Upadacitinib Adalimumab / Upadacitinib Upadacitinib / Adalimumab
Hide Arm/Group Description

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.

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.

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.

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.

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.

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.

All-Cause Mortality
Placebo Adalimumab Upadacitinib Placebo / Upadacitinib Adalimumab / Upadacitinib Upadacitinib / Adalimumab
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/652 (0.31%)      2/327 (0.61%)      0/650 (0.00%)      0/304 (0.00%)      0/77 (0.00%)      0/125 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Adalimumab Upadacitinib Placebo / Upadacitinib Adalimumab / Upadacitinib Upadacitinib / Adalimumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/652 (2.91%)      14/327 (4.28%)      24/650 (3.69%)      7/304 (2.30%)      0/77 (0.00%)      2/125 (1.60%)    
Cardiac disorders             
ACUTE MYOCARDIAL INFARCTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
ATRIAL FLUTTER  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
CARDIAC FAILURE  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
CARDIOGENIC SHOCK  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
LEFT VENTRICULAR FAILURE  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
MYOCARDIAL INFARCTION  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
RIGHT VENTRICULAR DILATATION  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Eye disorders             
CATARACT  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Gastrointestinal disorders             
DIARRHOEA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  2 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
FOOD POISONING  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
GASTRIC POLYPS  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
General disorders             
PYREXIA  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
SUDDEN DEATH  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Hepatobiliary disorders             
CHOLELITHIASIS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
HEPATITIS TOXIC  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Infections and infestations             
APPENDICITIS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 2/650 (0.31%)  2 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
BRONCHIOLITIS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
BRONCHITIS BACTERIAL  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
CELLULITIS  1  0/652 (0.00%)  0 2/327 (0.61%)  2 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
FALLOPIAN TUBE ABSCESS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
GASTROENTERITIS  1  3/652 (0.46%)  3 0/327 (0.00%)  0 2/650 (0.31%)  2 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
INFECTED BITE  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
INFECTIOUS COLITIS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
INFLUENZA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
KIDNEY INFECTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
LOWER RESPIRATORY TRACT INFECTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
LUNG INFECTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PERITONITIS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PNEUMOCYSTIS JIROVECII PNEUMONIA  1  2/652 (0.31%)  2 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PNEUMONIA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 1/125 (0.80%)  1
PYELONEPHRITIS ACUTE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
SEPSIS  1  1/652 (0.15%)  1 1/327 (0.31%)  1 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
SOFT TISSUE INFECTION  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
UROSEPSIS  1  0/652 (0.00%)  0 1/327 (0.31%)  1 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
VIRAL INFECTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Injury, poisoning and procedural complications             
AIRWAY COMPLICATION OF ANAESTHESIA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
CRANIOCEREBRAL INJURY  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
FALL  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
FIBULA FRACTURE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
HEAD INJURY  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
HIP FRACTURE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
SPINAL COMPRESSION FRACTURE  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
TIBIA FRACTURE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
TOXICITY TO VARIOUS AGENTS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
UPPER LIMB FRACTURE  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Musculoskeletal and connective tissue disorders             
ARTHRITIS  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
LUMBAR SPINAL STENOSIS  1  1/652 (0.15%)  1 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
NECK PAIN  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
OSTEOARTHRITIS  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
RHEUMATOID ARTHRITIS  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
VERTEBRAL LESION  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
BASAL CELL CARCINOMA  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
CERVIX CARCINOMA  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Nervous system disorders             
DEMYELINATION  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
DIZZINESS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
NEUROTOXICITY  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PARAPLEGIA  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
SEIZURE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 1/304 (0.33%)  1 0/77 (0.00%)  0 0/125 (0.00%)  0
SPINAL CORD HAEMORRHAGE  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
SYNCOPE  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Pregnancy, puerperium and perinatal conditions             
ABORTION SPONTANEOUS  1  0/652 (0.00%)  0 0/327 (0.00%)  0 2/650 (0.31%)  2 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Psychiatric disorders             
CONFUSIONAL STATE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Renal and urinary disorders             
BLADDER PROLAPSE  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
RENAL FAILURE  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
Reproductive system and breast disorders             
ENDOMETRIAL HYPERPLASIA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
MENORRHAGIA  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
OVARIAN CYST RUPTURED  1  1/652 (0.15%)  1 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
VAGINAL HAEMORRHAGE  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 1/125 (0.80%)  1
Respiratory, thoracic and mediastinal disorders             
ASTHMA  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
BRONCHOSPASM  1  0/652 (0.00%)  0 0/327 (0.00%)  0 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
IDIOPATHIC PULMONARY FIBROSIS  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PULMONARY EMBOLISM  1  1/652 (0.15%)  1 3/327 (0.92%)  3 1/650 (0.15%)  1 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
PULMONARY FIBROSIS  1  0/652 (0.00%)  0 1/327 (0.31%)  1 0/650 (0.00%)  0 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Adalimumab Upadacitinib Placebo / Upadacitinib Adalimumab / Upadacitinib Upadacitinib / Adalimumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   43/652 (6.60%)      16/327 (4.89%)      72/650 (11.08%)      9/304 (2.96%)      6/77 (7.79%)      4/125 (3.20%)    
Infections and infestations             
NASOPHARYNGITIS  1  19/652 (2.91%)  20 9/327 (2.75%)  10 36/650 (5.54%)  42 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
UPPER RESPIRATORY TRACT INFECTION  1  24/652 (3.68%)  24 7/327 (2.14%)  8 37/650 (5.69%)  43 0/304 (0.00%)  0 0/77 (0.00%)  0 0/125 (0.00%)  0
URINARY TRACT INFECTION  1  0/652 (0.00%)  0 0/327 (0.00%)  0 0/650 (0.00%)  0 9/304 (2.96%)  9 6/77 (7.79%)  6 4/125 (3.20%)  4
1
Term from vocabulary, MedDRA (19.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
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Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02629159     History of Changes
Other Study ID Numbers: M14-465
2015-003333-95 ( EudraCT Number )
First Submitted: December 10, 2015
First Posted: December 14, 2015
Results First Submitted: September 13, 2019
Results First Posted: October 7, 2019
Last Update Posted: October 7, 2019