A Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02955212
• Collaborator: (none)
• Enrollment: 338
• Locations: 43
• Arms: 2
• Actual Duration (Months): 32
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study objectives of Period 1 of this study were to compare the efficacy, safety, and tolerability of upadacitinib versus placebo for the treatment of signs and symptoms of subjects from China and selected countries including Brazil and South Korea with moderately to severely active rheumatoid arthritis (RA) who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs.

The study objective of Period 2 is to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in subjects with RA who have completed Period 1.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis (RA)	Drug: Upadacitinib; Drug: Placebo	Phase 3

Detailed Description

This is a Phase 3 multicenter study that includes two periods. Period 1 is a 12-week, randomized, double-blind, parallel-group, placebo-controlled period designed to compare the safety and efficacy of upadacitinib versus placebo for the treatment of signs and symptoms of participants with moderately to severely active RA who are on a stable dose of csDMARDs and have an inadequate response to csDMARDs. Period 2 is an open label 52 week extension period to evaluate the long-term safety, tolerability, and efficacy of upadacitinib in participants with RA who have completed Period 1.

Study Design

• Study Type: Interventional
• Actual Enrollment: 338 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study With Upadacitinib (ABT-494) in Subjects From China and Selected Countries With Moderately to Severely Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs)
• Actual Study Start Date: Jan 3, 2018
• Actual Primary Completion Date: Aug 14, 2019
• Actual Study Completion Date: Sep 3, 2020

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo / Upadacitinib 15 mg Participants randomized to receive placebo once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494 RINVOQ™ ; Drug: Placebo; Tablets for oral administration
Experimental: Upadacitinib 15 mg Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1 and up to an additional 52 weeks in Period 2.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494 RINVOQ™

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

1. Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) at Week 12 [Baseline and 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity. A negative change from Baseline in DAS28 (CRP) indicates improvement in disease activity.

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

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

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

   Low disease activity based on DAS28 (CRP) is defined a DAS28 (CRP) score of ≤ 3.2. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.

5. Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12 [Week 12]

   Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) score of less than 2.6. 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity.

6. Percentage of Participants Achieving Low Disease Activity Based on Clinical Disease Activity Index (CDAI) at Week 12 [Week 12]

   Low disease activity based on 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 76 with higher scores indicating higher disease activity.

7. Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12 [Baseline and 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).

8. Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12 [Baseline and 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).

9. Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1 [Baseline and Week 1]

   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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of RA for ≥ 3 months who also fulfill the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) classification criteria for RA.

• Participants have been receiving csDMARD therapy ≥ 3 months and on a stable dose for ≥ 4 weeks prior to the first dose of study drug.

1. Participants must have failed (lack of efficacy) at least one of the following: methotrexate (MTX), sulfasalazine, or leflunomide.

2. The following csDMARDs are allowed: oral or parenteral MTX, sulfasalazine, hydroxychloroquine, chloroquine, and leflunomide.

3. A combination of up to two background csDMARDs is allowed except the combination of MTX and leflunomide.

• Participant meets both of the following disease activity criteria:

1. ≥ 6 swollen joints (based on 66 joint counts) and ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits; and

2. High-sensitivity C-Reactive Protein (hsCRP) ≥ 3 mg/L at Screening

• Participants with prior exposure to at most one biological disease-modifying anti-rheumatic drugs (bDMARD) may be enrolled (up to 20% of total number of subjects).

Specifically, prior to enrollment:

1. Participants with limited exposure to bDMARD (< 3 months) OR

2. Participants who are responding to a bDMARD therapy but had to discontinue due to intolerability (regardless of treatment duration).

• Participants must have discontinued bDMARD therapy prior to the first dose of study drug.

Exclusion Criteria:

• Prior exposure to any Janus kinase (JAK) inhibitor (including but not limited to tofacitinib, baricitinib, and filgotinib).

• Participants who are considered inadequate responders (lack of efficacy) to bDMARD therapy as defined by the Investigator.

• History of any arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms]. Current diagnosis of secondary Sjogren's Syndrome is permitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ceti - Centro de Estudos Em Terapias Inovadoras Ltda /Id# 152964	Curitiba	Parana	Brazil	80030-110
2	Parana Medical Research Center /ID# 153507	Maringa	Parana	Brazil	87015-000
3	LMK Sevicos Medicos S/S /ID# 152963	Porto Alegre	Rio Grande Do Sul	Brazil	90480-000
4	Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto /ID# 152961	Sao Jose Do Rio Preto	Sao Paulo	Brazil	15090-000
5	CEPIC - Centro Paulista de Investigação Clínica e Serviços Médicos Ltda /ID# 152966	São Paulo	Sao Paulo	Brazil	04266-010
6	1st Aff Hosp of Bengbu Med Col /ID# 162161	Bengbu	Anhui	China	233099
7	Anhui Provincial Hospital /ID# 161117	Hefei	Anhui	China	230001
8	Zhongshan Hosp. of Fudan Uni. /ID# 161108	Shanghai	Anhui	China	200032
9	The 1st Aff Hosp Xiamen Univ /ID# 162154	Xiamen	Fujian	China	361003
10	Zhuzhou Central Hospital /ID# 162153	Zhuzhou	Hunan	China	412007
11	The First Affiliated Hospital /ID# 163747	Baotou	Inner Mongolia	China	014016
12	The First People's Hospital /ID# 168462	Changzhou	Jiangsu	China	213004
13	The First People's Hospital of Jiujiang /ID# 168461	Jiujiang	Jiangxi	China	332000
14	The First Hosp of Jilin Univ /ID# 161116	Changchun	Jilin	China	130021
15	Jining No.1 People's Hospital /ID# 162158	Jining	Shandong	China	272001
16	Shanghai Changhai Hospital /ID# 161123	Shanghai	Shanghai	China	200433
17	West China Hospital /ID# 161119	Chengdu	Sichuan	China	610041
18	Xuanwu Hosp Capital Med Univ /ID# 161118	Beijing		China	100053
19	Peking Union Med College Hosp /ID# 161107	Beijing		China	100730
20	The Second Xiangya Hospital of Central South University /ID# 162152	Changsha		China	410000
21	First Affiliated Hospital of Kunming Medical University /ID# 164637	Kunming		China	650032
22	Jiangsu Province Hospital /ID# 161122	Nanjing		China	210029
23	Pingxiang People's Hospital /ID# 162151	Pingxiang		China	337055
24	1st Aff Hosp of Shantou Univ /ID# 162165	Shantou Guangdong		China	515041
25	The Second Hospital of Shanxi /ID# 162164	Taiyuan		China	030001
26	Tianjin Med Univ General Hosp /ID# 162155	Tianjin		China	300052
27	People's Hospital of Xinjiang /ID# 162157	Urumqi		China	830001
28	First Affiliated Hospital of Xi'an Jiaotong University /ID# 162150	Xi'an		China	710061
29	SoonChunHyang University CheonAn Hospital /ID# 209078	Cheonan-si	Chungcheongnamdo	Korea, Republic of	31151
30	Kyungpook National Univ Hosp /ID# 166919	Daegu	Daegu Gwang Yeogsi	Korea, Republic of	41944
31	Chungnam National University Hospital /ID# 167727	Jung-gu	Daejeon Gwang Yeogsi	Korea, Republic of	35015
32	Ajou University Hospital /ID# 163912	Suwon-si	Gyeonggido	Korea, Republic of	16499
33	St. Vincent's Hospital /ID# 166918	Suwon	Gyeonggido	Korea, Republic of	16247
34	Inha University Hospital /ID# 163910	Jung-gu	Incheon Gwang Yeogsi	Korea, Republic of	22332
35	Chonnam National University Hospital /ID# 167726	Gwangju	Jeonranamdo	Korea, Republic of	61469
36	Kyung Hee University Medical Center /ID# 163908	Dongdaemun-gu	Seoul Teugbyeolsi	Korea, Republic of	02447
37	SMG-SNU Boramae Medical Center /ID# 163911	Dongjak-gu	Seoul Teugbyeolsi	Korea, Republic of	07061
38	Yonsei University Health System, Severance Hospital /ID# 168421	Seodaemun-gu	Seoul Teugbyeolsi	Korea, Republic of	03722
39	Hanyang University Seoul Hospi /ID# 163913	Seongdong-gu	Seoul Teugbyeolsi	Korea, Republic of	04763
40	Konkuk University Medical Ctr /ID# 206148	Seoul	Seoul Teugbyeolsi	Korea, Republic of	05030
41	The Catholic University of Korea, Yeouido St. Mary's Hospital /ID# 204224	Seoul	Seoul Teugbyeolsi	Korea, Republic of	07345
42	Asan Medical Center /ID# 163909	Seoul		Korea, Republic of	05505
43	Chung-Ang University Hostipal /ID# 209076	Seoul		Korea, Republic of	06973

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

• Study Protocol - Oct 17, 2018
• Statistical Analysis Plan - May 30, 2019

More Information

Publications

None provided.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02955212
• Other Study ID Numbers: M15-557
• First Posted: Nov 4, 2016
• Last Update Posted: Sep 27, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by AbbVie: Rheumatoid Arthritis; Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs); ABT-494
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Rheumatic Diseases; Upadacitinib

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at 37 sites in Brazil, China, and South Korea. The study consisted of a 12-week placebo-controlled, double-blind period (Period 1), and an open-label 52-week extension period (Period 2).
Pre-assignment Detail	Participants who met eligibility criteria were randomized in a 1:1 ratio to one of two treatment groups. Randomization was stratified by country and the Chinese population was expected to comprise up to 80% of the total study population.

Arm/Group Title	Placebo / Upadacitinib 15 mg	Upadacitinib 15 mg / Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1 followed by upadacitinib 15 mg once daily for up to 52 weeks in Period 2.
Period Title: Period 1: Double-blind Treatment Period
STARTED	169	169
COMPLETED	153	157
NOT COMPLETED	16	12
Period Title: Period 1: Double-blind Treatment Period
STARTED	153	157
COMPLETED	136	139
NOT COMPLETED	17	18

Baseline Characteristics

Arm/Group Title	Placebo	Upadacitinib 15 mg	Total
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.	Total of all reporting groups
Overall Participants	169	169	338
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.7 (11.39)	51.7 (10.63)	51.7 (11.00)
Sex: Female, Male (Count of Participants)
Female	139 82.2%	135 79.9%	274 81.1%
Male	30 17.8%	34 20.1%	64 18.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	21 12.4%	24 14.2%	45 13.3%
Not Hispanic or Latino	148 87.6%	145 85.8%	293 86.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	19 11.2%	19 11.2%	38 11.2%
Black or African American	3 1.8%	3 1.8%	6 1.8%
American Indian/Alaska Native	0 0%	0 0%	0 0%
Native Hawaiian or other Pacific Islander	0 0%	0 0%	0 0%
Asian	142 84%	141 83.4%	283 83.7%
Multiple	5 3%	6 3.6%	11 3.3%
Enrollment by Country (Count of Participants)
China	114 67.5%	114 67.5%	228 67.5%
South Korea	29 17.2%	29 17.2%	58 17.2%
Brazil	26 15.4%	26 15.4%	52 15.4%
Duration Since Rheumatoid Arthritis (RA) Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.5 (7.55)	7.2 (7.16)	7.3 (7.35)
Tender Joint Count (joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joints]	23.0 (14.45)	21.5 (14.84)	22.3 (14.64)
Swollen Joint Count (joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joints]	11.9 (6.00)	11.9 (6.89)	11.9 (6.45)
Patient's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	63.9 (22.32)	64.4 (20.52)	64.1 (21.41)
Physician's Global Assessment of Disease Activity (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	67.0 (13.83)	66.7 (17.51)	66.9 (15.74)
Patient's Assessment of Pain (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	63.8 (20.62)	66.8 (20.59)	65.3 (20.63)
Health Assessment Questionnaire - Disability Index (HAQ-DI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.4 (0.65)	1.3 (0.66)	1.3 (0.65)
High-sensitivity C-reactive Protein (CRP) (mg/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/L]	20.2 (25.15)	20.0 (21.46)	20.1 (23.34)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12
Description	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).
Time Frame	Baseline and Week 12

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	31.4 18.6%	71.6 42.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	40.2
	Confidence Interval	(2-Sided) 95%; 30.5 to 50.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

2. Secondary Outcome

Title	Change From Baseline in Disease Activity Score Based on CRP (DAS28 [CRP]) at Week 12
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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Least Squares Mean (95% Confidence Interval) [units on a scale]	-0.95	-2.56

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including treatment as the fixed factor, and Baseline value and the stratification factor country as the covariates.
Method of Estimation	Estimation Parameter	Least Squares (LS) Mean Difference
	Estimated Value	-1.61
	Confidence Interval	(2-Sided) 95%; -1.86 to -1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean Difference = Upadacitinib - Placebo

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Least Squares Mean (95% Confidence Interval) [units on a scale]	-0.18	-0.62

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments	ANCOVA model including treatment as the fixed factor, and Baseline value and the stratification factor country as the covariates.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean Difference = Upadacitinib - Placebo

4. Secondary Outcome

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

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	149	143
Least Squares Mean (95% Confidence Interval) [units on a scale]	3.36	8.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed Effect Model Repeat Measurement
	Comments	MMRM model with treatment, visit, treatment-by-visit interaction and stratification factor of country as fixed effects and Baseline value as covariate
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.57
	Confidence Interval	(2-Sided) 95%; 4.13 to 7.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	LS Mean Difference = Upadacitinib - Placebo

5. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28 (CRP) at Week 12
Description	Low disease activity based on DAS28 (CRP) is defined a DAS28 (CRP) score of ≤ 3.2. The DAS28 is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity. A DAS28 score less than or equal to 3.2 indicates low disease activity.
Time Frame	Week 12

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	13.6 8%	46.2 27.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	32.5
	Confidence Interval	(2-Sided) 95%; 23.4 to 41.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

6. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission Based on DAS28 (CRP) at Week 12
Description	Clinical remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) score of less than 2.6. 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), and hsCRP (in mg/L). Scores on the DAS28 range from 0 to 10, where higher scores indicate more disease activity.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	5.3 3.1%	29.6 17.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	24.3
	Confidence Interval	(2-Sided) 24.3%; 16.6 to 31.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

7. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity Based on Clinical Disease Activity Index (CDAI) at Week 12
Description	Low disease activity based on 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 76 with higher scores indicating higher disease activity.
Time Frame	Week 12

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	11.2 6.6%	35.5 21%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	24.3
	Confidence Interval	(2-Sided) 95%; 15.6 to 32.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

8. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Description	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).
Time Frame	Baseline and Week 12

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	8.3 4.9%	40.8 24.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	32.5
	Confidence Interval	(2-Sided) 95%; 24.0 to 41.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

9. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Description	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).
Time Frame	Baseline and Week 12

Outcome Measure Data

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	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	3.6 2.1%	21.3 12.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country.
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	17.8
	Confidence Interval	(2-Sided) 95%; 11.0 to 24.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

10. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 1
Description	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).
Time Frame	Baseline and Week 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Upadacitinib 15 mg
Arm/Group Description	Participants randomized to receive placebo once daily for 12 weeks in Period 1.	Participants randomized to receive upadacitinib 15 mg once daily for 12 weeks in Period 1.
Measure Participants	169	169
Number (95% Confidence Interval) [percentage of participants]	5.9 3.5%	25.4 15%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 15 mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel test adjusted for the stratification factor of country
Method of Estimation	Estimation Parameter	Response Rate Difference
	Estimated Value	19.5
	Confidence Interval	(2-Sided) 95%; 12.1 to 27.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Response Rate Difference = Upadacitinib - Placebo

Adverse Events

Time Frame	Period 1: From the first dose of study drug up to Week 12 or up to 30 days after last dose for participants who discontinued study drug prior to Week 12. Period 2: From Week 12 to 30 days after last dose; up to 56 weeks.
Arm/Group Title	Period 1: Placebo		Period 1: Upadacitinib 15 mg		Period 1+2: Upadacitinib 15 mg
Arm/Group Description	Participants received placebo once daily for 12 weeks in Period 1.		Participants received upadacitinib 15 mg once daily for 12 weeks in Period 1.		Participants originally assigned to placebo received upadacitinib 15 mg from Week 12 to Week 64. Participants originally assigned to upadacitinib received upadacitinib 15 mg from Week 0 to Week 64.
All Cause Mortality
	Period 1: Placebo		Period 1: Upadacitinib 15 mg		Period 1+2: Upadacitinib 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/169 (0%)		0/169 (0%)		0/322 (0%)
Serious Adverse Events
	Period 1: Placebo		Period 1: Upadacitinib 15 mg		Period 1+2: Upadacitinib 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/169 (3%)		12/169 (7.1%)		55/322 (17.1%)
Cardiac disorders
ACUTE MYOCARDIAL INFARCTION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Eye disorders
CATARACT	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Gastrointestinal disorders
DUODENAL ULCER PERFORATION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
UPPER GASTROINTESTINAL HAEMORRHAGE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Hepatobiliary disorders
DRUG-INDUCED LIVER INJURY	1/169 (0.6%)	1	0/169 (0%)	0	0/322 (0%)	0
CHOLECYSTITIS ACUTE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
CHOLELITHIASIS	0/169 (0%)	0	0/169 (0%)	0	3/322 (0.9%)	3
Immune system disorders
ANAPHYLACTIC REACTION	0/169 (0%)	0	1/169 (0.6%)	1	0/322 (0%)	0
Infections and infestations
HERPES ZOSTER	0/169 (0%)	0	1/169 (0.6%)	1	4/322 (1.2%)	4
PNEUMONIA	1/169 (0.6%)	1	3/169 (1.8%)	3	8/322 (2.5%)	8
ANAL ABSCESS	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
APPENDICITIS	0/169 (0%)	0	0/169 (0%)	0	2/322 (0.6%)	2
BACTERIAL INFECTION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
FALLOPIAN TUBE ABSCESS	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
FEBRILE INFECTION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
INFLUENZA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
LUNG INFECTION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
ORAL HERPES	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
OTITIS MEDIA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
PNEUMONIA CRYPTOCOCCAL	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
POSTOPERATIVE WOUND INFECTION	0/169 (0%)	0	0/169 (0%)	0	2/322 (0.6%)	2
SINUSITIS FUNGAL	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Injury, poisoning and procedural complications
MENISCUS INJURY	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
TENDON RUPTURE	0/169 (0%)	0	2/169 (1.2%)	2	2/322 (0.6%)	3
ANKLE FRACTURE	0/169 (0%)	0	0/169 (0%)	0	2/322 (0.6%)	2
ARTHROPOD BITE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
FIBULA FRACTURE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
HUMERUS FRACTURE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
PATELLA FRACTURE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
PROCEDURAL HAEMORRHAGE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
SPINAL COMPRESSION FRACTURE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
TIBIA FRACTURE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Metabolism and nutrition disorders
DECREASED APPETITE	1/169 (0.6%)	1	0/169 (0%)	0	0/322 (0%)	0
ELECTROLYTE IMBALANCE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Musculoskeletal and connective tissue disorders
LUMBAR SPINAL STENOSIS	1/169 (0.6%)	1	0/169 (0%)	0	1/322 (0.3%)	1
RHEUMATOID ARTHRITIS	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
SENILE OSTEOPOROSIS	1/169 (0.6%)	1	0/169 (0%)	0	0/322 (0%)	0
SPINAL LIGAMENT OSSIFICATION	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
SPONDYLOLISTHESIS	1/169 (0.6%)	1	0/169 (0%)	0	0/322 (0%)	0
ARTHRALGIA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
OSTEONECROSIS	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BREAST CANCER	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
ACOUSTIC NEUROMA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
KAPOSI'S SARCOMA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
SQUAMOUS CELL CARCINOMA OF THE CERVIX	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Nervous system disorders
CEREBRAL INFARCTION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
POST HERPETIC NEURALGIA	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Renal and urinary disorders
URETEROLITHIASIS	1/169 (0.6%)	1	0/169 (0%)	0	0/322 (0%)	0
STRESS URINARY INCONTINENCE	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
PULMONARY EMBOLISM	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
Skin and subcutaneous tissue disorders
ANGIOEDEMA	0/169 (0%)	0	1/169 (0.6%)	1	1/322 (0.3%)	1
Surgical and medical procedures
ABORTION INDUCED	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Vascular disorders
HYPERTENSION	0/169 (0%)	0	0/169 (0%)	0	1/322 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Period 1: Placebo		Period 1: Upadacitinib 15 mg		Period 1+2: Upadacitinib 15 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/169 (7.7%)		25/169 (14.8%)		198/322 (61.5%)
Blood and lymphatic system disorders
ANAEMIA	0/169 (0%)	0	0/169 (0%)	0	26/322 (8.1%)	30
LEUKOPENIA	0/169 (0%)	0	0/169 (0%)	0	26/322 (8.1%)	37
NEUTROPENIA	0/169 (0%)	0	0/169 (0%)	0	20/322 (6.2%)	27
Hepatobiliary disorders
HEPATIC FUNCTION ABNORMAL	0/169 (0%)	0	0/169 (0%)	0	27/322 (8.4%)	34
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION	11/169 (6.5%)	13	16/169 (9.5%)	16	65/322 (20.2%)	95
HERPES ZOSTER	0/169 (0%)	0	0/169 (0%)	0	23/322 (7.1%)	24
LATENT TUBERCULOSIS	0/169 (0%)	0	0/169 (0%)	0	18/322 (5.6%)	18
NASOPHARYNGITIS	0/169 (0%)	0	0/169 (0%)	0	24/322 (7.5%)	29
URINARY TRACT INFECTION	0/169 (0%)	0	0/169 (0%)	0	19/322 (5.9%)	21
Investigations
ALANINE AMINOTRANSFERASE INCREASED	2/169 (1.2%)	2	9/169 (5.3%)	13	30/322 (9.3%)	43
ASPARTATE AMINOTRANSFERASE INCREASED	0/169 (0%)	0	0/169 (0%)	0	24/322 (7.5%)	33
BLOOD CREATINE PHOSPHOKINASE INCREASED	0/169 (0%)	0	0/169 (0%)	0	29/322 (9%)	37
WEIGHT INCREASED	0/169 (0%)	0	0/169 (0%)	0	23/322 (7.1%)	31
Vascular disorders
HYPERTENSION	0/169 (0%)	0	0/169 (0%)	0	18/322 (5.6%)	18

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.