A Study Investigating the Efficacy and Safety of Upadacitinib (ABT-494) Given With Methotrexate (MTX) in Adults With Rheumatoid Arthritis Who Have Had an Inadequate Response to MTX Alone

• Sponsor: AbbVie (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02066389
• Collaborator: (none)
• Enrollment: 300
• Locations: 63
• Arms: 6
• Actual Duration (Months): 15.2
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of the study was to compare the safety and efficacy of multiple doses of upadacitinib versus placebo in adults with moderately to severely active rheumatoid arthritis (RA) on stable background methotrexate therapy who had not shown an adequate response to methotrexate alone.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Placebo; Drug: Upadacitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 300 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Investigate the Safety and Efficacy of ABT-494 With Background Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis (RA) Who Have Had an Inadequate Response to MTX Alone
• Actual Study Start Date: Mar 26, 2014
• Actual Primary Completion Date: Jul 2, 2015
• Actual Study Completion Date: Jul 2, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Participants received placebo capsules twice daily for 12 weeks.	Drug: Placebo; Tablets for oral administration
Experimental: Upadacitinib 3 mg BID Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494
Experimental: Upadacitinib 6 mg BID Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494
Experimental: Upadacitinib 12 mg BID Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494
Experimental: Upadacitinib 18 mg BID Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494
Experimental: Upadacitinib 24 mg QD Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.	Drug: Upadacitinib; Tablets for oral administration; Other Names: ABT-494

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

   A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 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's global assessment of disease activity Patient's global assessment of disease activity Patient's assessment of pain Health Assessment Questionnaire - Disability Index (HAQ-DI) High sensitivity C-reactive protein (hsCRP).

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

   A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in tender joint count; ≥ 70% improvement in 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).

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

   The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale (VAS) from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity. LDA is defined as a DAS28(CRP) score < 3.2.

4. Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12 [Week 12]

   The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to 10 where higher scores indicate more disease activity. CR is defined as a DAS28(CRP) score < 2.6.

5. Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12 [Week 12]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, 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. LDA is defined as a CDAI score ≤ 10.

6. Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12 [Week 12]

   The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, 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. CR is defined as a CDAI score ≤ 2.8.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with RA based on either the 1987-revised American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European League against Rheumatism (EULAR) criteria for ≥ 3 months.

2. Have active RA as defined by the following minimum disease activity criteria:

• ≥ 6 swollen joints (based on 66 joint counts) at Screening and Baseline Visits.

• ≥ 6 tender joints (based on 68 joint counts) at Screening and Baseline Visits.

• high-sensitivity C-reactive protein (hsCRP) > upper limit of normal (ULN) OR positive for both rheumatoid factor and anti-cyclic citrullinated peptide (CCP) at Screening.

1. Subjects must have been receiving oral or parenteral methotrexate therapy ≥ 3 months and on a stable prescription of 7.5 to 25 mg/week for at least 4 weeks prior to Baseline Visit. Subjects should also be on a stable dose of folic acid (or equivalent) for at least 4 weeks prior to Baseline Visit. Subjects should continue with their stable doses of methotrexate and folic acid throughout the study.

2. Except for MTX, subjects must have discontinued all oral disease-modifying anti-rheumatic drugs (DMARDs) prior to Baseline Visit as specified below or for at least five times the mean terminal elimination half-life of a drug, whichever is longer:

• ≥ 4 weeks prior to Baseline Visit for minocycline, penicillamine, sulfasalazine, hydroxychloroquine, chloroquine, azathioprine, gold formulations, cyclophosphamide

• ≥ 8 weeks prior to Baseline Visit for leflunomide if no elimination procedure was followed, or adhere to a washout procedure (i.e., 11 days washout with colestyramine, or 30 days washout with activated charcoal)

1. Subject has a negative tuberculosis (TB) Screening Assessment. If the subject has evidence of a latent TB infection, the subject must initiate and complete a minimum of 2 weeks (or per local guidelines, whichever is longer) of an ongoing TB prophylaxis or have documented completion of a full course of TB prophylaxis, prior to Baseline Visit.

2. Subjects can be taking non-steroidal anti-inflammatory drugs (NSAIDS), acetaminophen, oral corticosteroids (equivalent to prednisone ≤ 10 mg), or inhaled corticosteroids at a stable dose for at least 4 weeks prior to Baseline Visit for stable medical conditions and should be kept at a stable dose throughout the study. NSAIDs, acetaminophen, tramadol, codeine, hydrocodone and propoxyphene taken as needed are allowed but may not be taken 24 hours prior to any study visit. Oral and inhaled corticosteroids taken as needed are allowed but may not be taken 24 hours prior to any study visit.

3. Subjects must have discontinued high potency opiates including (but not limited to): oxycodone, oxymorphone, fentanyl, levorphanol, buprenorphine, methadone, hydromorphone, and morphine at least 4 weeks prior to Baseline Visit.

Exclusion Criteria:

1. Female who is pregnant or breastfeeding.

2. Prior exposure to Janus activated kinase (JAK) inhibitor (e.g., tofacitinib, baricitinib).

3. Prior exposure to any investigational or approved biologic RA therapy.

4. Receipt of any investigational drug of chemical or biologic nature within a minimum of 30 days or 5 half-lives of the drug (whichever is longer) prior to Week 0 Visit.

5. Current or expected need of other immunosuppressant medications, except methotrexate. Use of oral intake of > 10 mg prednisone/day or equivalent corticosteroid therapy (see inclusion criterion 7).

6. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the preceding 8 weeks prior to the Week 0 Visit.

7. Screening laboratory values meeting the following criteria:

• Serum aspartate transaminase (AST) or alanine transaminase (ALT) > 1.5 × ULN

• Estimated glomerular filtration rate (eGRF) by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 40 mL/min/1.73 m²

• Total white blood cell count (WBC) < 3,000/µL

• Absolute neutrophil count (ANC) < 1,200/µL

• Platelet count < 100,000/µL

• Absolute lymphocytes count < 750/ µL

• Hemoglobin < 9 gm/dL

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	C.V. Mehta MD, Med Corporation /ID# 126380	Hemet	California	United States	92543
2	Omega Research Consultants, LLC /ID# 125780	DeBary	Florida	United States	32713-2260
3	Lovelace Scientific Resources /ID# 127324	Venice	Florida	United States	34292
4	North Georgia Rheumatology Grp /ID# 125779	Lawrenceville	Georgia	United States	30045
5	PRN Professional Research Network of Kansas, LLC /ID# 126148	Wichita	Kansas	United States	67205
6	The Center for Rheumatology & /ID# 127323	Wheaton	Maryland	United States	20902
7	Summit Medical Group /ID# 125776	Clifton	New Jersey	United States	07012
8	Arthritis and Osteo Assoc /ID# 134994	Las Cruces	New Mexico	United States	88011
9	Altoona Ctr Clinical Res /ID# 125777	Duncansville	Pennsylvania	United States	16635
10	Emkey Arthritis and Osteo Clin /ID# 134716	Wyomissing	Pennsylvania	United States	19610
11	Accurate Clinical Research /ID# 126535	Houston	Texas	United States	77034
12	Mountain State Clinical Resear /ID# 127089	Clarksburg	West Virginia	United States	26301
13	MHAT Trimontsium /ID# 127311	Plovdiv		Bulgaria	4000
14	UMHAT Pulmed OOD /ID# 127307	Plovdiv		Bulgaria	4000
15	MHAT Kaspela /ID# 127315	Plovdiv		Bulgaria	4001
16	Diagnostic Consultative Center /ID# 127313	Sofia		Bulgaria	1612
17	UMHAT Sv. Ivan Rilski /ID# 127314	Sofia		Bulgaria	1612
18	UMHAT Sv. Ivan Rilski /ID# 131608	Sofia		Bulgaria	1612
19	Diagnostic Consultative Center /ID# 127312	Varna		Bulgaria	9000
20	Corp de Beneficencia Osorno /ID# 127337	Osorno		Chile	1710216
21	Quantum Research LTDA. /ID# 127338	Puerto Varas		Chile	5550170
22	Revmatologicky ustav Praha /ID# 127317	Prague 2	Praha 2	Czechia	128 00
23	Nuselská poliklinika, Revmatologie /ID# 127318	Prague 4	Praha 4	Czechia	140 00
24	Revmatologie Bruntal, s.r.o /ID# 126881	Bruntál		Czechia	79201
25	Artroscan s.r.o. /ID# 126845	Ostrava		Czechia	722 00
26	Qualiclinic Kft. /ID# 127340	Budapest III	Pest	Hungary	1036
27	Veszprem Megyei Csolnoky Feren /ID# 126876	Veszprém		Hungary	8200
28	Barzilai Medical Center /ID# 126875	Ashkelon		Israel	78278
29	Rambam Health Care Campus /ID# 127341	Haifa		Israel	3109601
30	Sheba Medical Center /ID# 126878	Ramat Gan		Israel	5262100
31	LTD M&M Centers /ID# 127346	Adazi		Latvia	2164
32	Arija's Ancane's Family Doctor /ID# 127342	Baldone		Latvia	2125
33	Clinic ORTO /ID# 127345	Riga		Latvia	1005
34	Hospital de Jesús Nazareno /ID# 127352	Mexico City		Mexico	06090
35	Cliditer SA de CV /ID# 127347	Mexico City		Mexico	06700
36	Clinstile, S.A. de C.V. /ID# 127350	Mexico City		Mexico	06700
37	REUMED Sp.z o.o. Filia nr 1 /ID# 127353	Lublin	Lubelskie	Poland	20-607
38	Centrum Medyczne Pratia Krakow /ID# 127358	Krakow	Malopolskie	Poland	30-002
39	NBR Polska /ID# 127359	Warsaw	Mazowieckie	Poland	00-465
40	Medica Pro Familia S.A Warszawa /ID# 127361	Warsaw	Mazowieckie	Poland	01-869
41	Gabinet Internistyczno Reum. /ID# 127357	Białystok	Podlaskie	Poland	15-099
42	Centrum Medyczne Pratia Gdynia /ID# 127360	Gdynia	Pomorskie	Poland	81-338
43	Michal Bazela Higher-Med /ID# 127355	Elbląg	Warminsko-mazurskie	Poland	82-300
44	GCM Medical Group /ID# 127363	San Juan		Puerto Rico	00909
45	City Clinical Hospital #7 /ID# 127372	Kazan	Tatarstan, Respublika	Russian Federation	420103
46	Tver Regional Clinical Hosp. /ID# 127375	Tver	Tverskaya Oblast	Russian Federation	170036
47	II Dzhan Research Center /ID# 127376	St. Petersburg		Russian Federation	192242
48	MEDMAN s.r.o. /ID# 127381	Martin		Slovakia	036 01
49	Poliklinika Senica /ID# 127396	Senica		Slovakia	905 01
50	Panorama Medical Centre /ID# 126846	Cape Town	Western Cape	South Africa	7500
51	Winelands Medical Research Ctr /ID# 126844	Stellenbosch	Western Cape	South Africa	7600
52	Hospital Regional de Malaga /ID# 127385	Málaga	Malaga	Spain	29009
53	Hospital Plató /ID# 127384	Barcelona		Spain	08006
54	Hospital CIMA Sanitas /ID# 127383	Barcelona		Spain	08034
55	Hospital Universitario Basurto /ID# 127391	Bilbao		Spain	48013
56	Hospital Clin Univ San Carlos /ID# 127382	Madrid		Spain	28040
57	Clinica Gaias /ID# 127386	Santiago de Compostela		Spain	15702
58	Hospital Infanta Luisa /ID# 127389	Sevilla		Spain	41010
59	Hospital Universitario de Valm /ID# 127387	Sevilla		Spain	41014
60	Medeniyet Univ. Goztepe Traini /ID# 132396	Istanbul		Turkey	34000
61	Kiev Municipal Clin Hosp 3 /ID# 127419	Kiev		Ukraine	02125
62	NSC-Strazhesko Ist Cardiology /ID# 127416	Kiev		Ukraine	03680
63	Sumy State University /ID# 127418	Sumy		Ukraine	40000

Sponsors and Collaborators

• AbbVie

Investigators

• Study Director: AbbVie Inc., AbbVie

Study Documents (Full-Text)

None provided.

More Information

Publications

• Genovese MC, Smolen JS, Weinblatt ME, Burmester GR, Meerwein S, Camp HS, Wang L, Othman AA, Khan N, Pangan AL, Jungerwirth S. Efficacy and Safety of ABT-494, a Selective JAK-1 Inhibitor, in a Phase IIb Study in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate. Arthritis Rheumatol. 2016 Dec;68(12):2857-2866. doi: 10.1002/art.39808.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02066389
• Other Study ID Numbers: M13-537; 2013-003984-72
• First Posted: Feb 19, 2014
• Last Update Posted: Jul 30, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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.: No
• Keywords provided by AbbVie: Musculoskeletal Disease; Arthritis; Joint Diseases; anti-inflammatory agents; antirheumatic agents
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Upadacitinib

Study Results

Participant Flow

Recruitment Details	A total of 300 adults with rheumatoid arthritis (RA) were enrolled at 59 study sites located in 16 countries.
Pre-assignment Detail	Eligible participants were randomly assigned in a 1:1:1:1:1:1 ratio to receive 1 of 5 doses of upadacitinib or placebo for 12 weeks. Participants who completed the 12-week treatment period completed a 30-day follow-up visit or had the option to enter an open-label extension study M13-538 (NCT02049138).

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Period Title: Overall Study
STARTED	50	50	50	50	50	50
Received Study Drug	50	50	50	50	50	49
COMPLETED	45	49	44	47	43	45
NOT COMPLETED	5	1	6	3	7	5

Baseline Characteristics

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD	Total
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.	Total of all reporting groups
Overall Participants	50	50	50	50	50	49	299
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.5 (11.51)	53.1 (12.15)	54.8 (12.47)	55.7 (11.65)	54.6 (13.65)	56.2 (11.79)	54.8 (12.16)
Age, Customized (Count of Participants)
18 to < 45 years	9 18%	11 22%	9 18%	7 14%	13 26%	7 14.3%	56 18.7%
45 to < 65 years	32 64%	30 60%	30 60%	32 64%	25 50%	27 55.1%	176 58.9%
≤ 65 years	9 18%	9 18%	11 22%	11 22%	12 24%	15 30.6%	67 22.4%
Sex: Female, Male (Count of Participants)
Female	38 76%	40 80%	34 68%	41 82%	42 84%	42 85.7%	237 79.3%
Male	12 24%	10 20%	16 32%	9 18%	8 16%	7 14.3%	62 20.7%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 22%	8 16%	17 34%	17 34%	7 14%	8 16.3%	68 22.7%
Not Hispanic or Latino	39 78%	42 84%	33 66%	33 66%	43 86%	41 83.7%	231 77.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	50 100%	48 96%	49 98%	48 96%	49 98%	49 100%	293 98%
Black or African American	0 0%	1 2%	1 2%	1 2%	0 0%	0 0%	3 1%
Multi-race	0 0%	1 2%	0 0%	1 2%	1 2%	0 0%	3 1%

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

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	46	48	49	49	47	49
Number [percentage of participants]	50.0 100%	64.6 129.2%	73.5 147%	81.6 163.2%	76.6 153.2%	81.6 166.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.153
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12
Description	A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 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's global assessment of disease activity Patient's global assessment of disease activity Patient's 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

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	46	48	49	50	47	48
Number [percentage of participants]	19.6 39.2%	39.6 79.2%	49.0 98%	50.0 100%	44.7 89.4%	43.8 89.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

3. Secondary Outcome

Title	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12
Description	A participant was a responder if the following 3 criteria for improvement from baseline were met: ≥ 70% improvement in tender joint count; ≥ 70% improvement in 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

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	46	47	49	50	47	48
Number [percentage of participants]	6.5 13%	23.4 46.8%	30.6 61.2%	16.0 32%	27.7 55.4%	25.0 51%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.023
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.145
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

4. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on DAS28(CRP) at Week 12
Description	The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale (VAS) from 0 to 100 mm). DAS28(CRP) scores range from 0 to approximately 10 where higher scores indicate more disease activity. LDA is defined as a DAS28(CRP) score < 3.2.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	47	49	49	50	49	49
Number [percentage of participants]	21.3 42.6%	49.0 98%	57.1 114.2%	46.0 92%	51.0 102%	42.9 87.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.010
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Fisher Exact
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Secondary: Percentage of Participants Achieving Clinical Remission (CR) Based on DAS28(CRP) at Week 12
Description	The disease activity score-28-CRP (DAS28 [CRP]) assesses RA disease activity based on a continuous scale of combined measures of 28 tender joint counts (TJC28), 28 swollen joint counts (SJC28), C-reactive protein (CRP), and the patient global assessment of disease activity (measured on a visual analog scale from 0 to 100 mm). DAS28(CRP) scores range from 0 to 10 where higher scores indicate more disease activity. CR is defined as a DAS28(CRP) score < 2.6.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	47	49	49	50	49	49
Number [percentage of participants]	14.9 29.8%	36.7 73.4%	38.8 77.6%	34.0 68%	42.9 85.8%	22.4 45.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.029
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.343
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

6. Secondary Outcome

Title	Percentage of Participants Achieving Low Disease Activity (LDA) Based on CDAI at Week 12
Description	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, 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. LDA is defined as a CDAI score ≤ 10.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	47	49	49	50	49	49
Number [percentage of participants]	21.3 42.6%	40.8 81.6%	40.8 81.6%	40.0 80%	49.0 98%	36.7 74.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Percentage of Participants Achieving Clinical Remission Based on CDAI at Week 12
Description	The clinical disease activity index (CDAI) is a composite index for assessing disease activity based on the summation of the counts of TJC28 and SJC28, 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. CR is defined as a CDAI score ≤ 2.8.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least 1 dose of study drug; last observation carried forward (LOCF) imputation was used for participants with missing data at Week 12 if prior post-baseline data were available.

Arm/Group Title	Placebo	Upadacitinib 3 mg BID	Upadacitinib 6 mg BID	Upadacitinib 12 mg BID	Upadacitinib 18 mg BID	Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.	Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.	Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
Measure Participants	47	49	49	50	49	49
Number [percentage of participants]	4.3 8.6%	12.2 24.4%	14.3 28.6%	6.0 12%	14.3 28.6%	6.1 12.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 3 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.269
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 6 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 12 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 18 mg BID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.160
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Upadacitinib 24 mg QD
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	Statistical tests were 1-sided at a significance level of 0.05.
	Method	Chi-squared
	Comments

Adverse Events

Time Frame	From the first dose of study drug until 30 days after last dose (up to 16 weeks).
Arm/Group Title	Placebo		Upadacitinib 3 mg BID		Upadacitinib 6 mg BID		Upadacitinib 12 mg BID		Upadacitinib 18 mg BID		Upadacitinib 24 mg QD
Arm/Group Description	Participants received placebo capsules twice daily for 12 weeks.		Participants received 3 mg upadacitinib twice daily (BID) for 12 weeks.		Participants received 6 mg upadacitinib twice daily (BID) for 12 weeks.		Participants received 12 mg upadacitinib twice daily (BID) for 12 weeks.		Participants received 18 mg upadacitinib twice daily (BID) for 12 weeks.		Participants received 24 mg upadacitinib once daily (QD) for 12 weeks.
All Cause Mortality
	Placebo		Upadacitinib 3 mg BID		Upadacitinib 6 mg BID		Upadacitinib 12 mg BID		Upadacitinib 18 mg BID		Upadacitinib 24 mg QD
	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	0/50 (0%)		0/50 (0%)		0/50 (0%)		0/50 (0%)		0/50 (0%)		0/49 (0%)
Serious Adverse Events
	Placebo		Upadacitinib 3 mg BID		Upadacitinib 6 mg BID		Upadacitinib 12 mg BID		Upadacitinib 18 mg BID		Upadacitinib 24 mg QD
	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	0/50 (0%)		0/50 (0%)		2/50 (4%)		1/50 (2%)		3/50 (6%)		2/49 (4.1%)
General disorders
PYREXIA	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/49 (0%)	0
Infections and infestations
PNEUMONIA	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/50 (0%)	0	0/49 (0%)	0
Injury, poisoning and procedural complications
FOREARM FRACTURE	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/49 (2%)	1
HEAD INJURY	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/49 (2%)	1
Musculoskeletal and connective tissue disorders
OSTEONECROSIS	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/50 (0%)	0	0/50 (0%)	0	0/49 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
LUNG NEOPLASM MALIGNANT	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/50 (0%)	0	0/50 (0%)	0	0/49 (0%)	0
Nervous system disorders
SCIATICA	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/49 (0%)	0
SYNCOPE	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/49 (2%)	1
Reproductive system and breast disorders
OVARIAN CYST	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	0/49 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Upadacitinib 3 mg BID		Upadacitinib 6 mg BID		Upadacitinib 12 mg BID		Upadacitinib 18 mg BID		Upadacitinib 24 mg QD
	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	2/50 (4%)		5/50 (10%)		7/50 (14%)		17/50 (34%)		6/50 (12%)		6/49 (12.2%)
Blood and lymphatic system disorders
LEUKOPENIA	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	3/50 (6%)	3	1/50 (2%)	1	0/49 (0%)	0
Gastrointestinal disorders
DIARRHOEA	0/50 (0%)	0	0/50 (0%)	0	1/50 (2%)	1	3/50 (6%)	3	1/50 (2%)	1	1/49 (2%)	1
Infections and infestations
INFLUENZA	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	4/50 (8%)	4	1/50 (2%)	1	0/49 (0%)	0
NASOPHARYNGITIS	1/50 (2%)	1	1/50 (2%)	1	2/50 (4%)	2	4/50 (8%)	4	2/50 (4%)	2	3/49 (6.1%)	3
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED	0/50 (0%)	0	0/50 (0%)	0	0/50 (0%)	0	3/50 (6%)	3	2/50 (4%)	2	1/49 (2%)	1
Metabolism and nutrition disorders
DYSLIPIDAEMIA	0/50 (0%)	0	1/50 (2%)	1	0/50 (0%)	0	3/50 (6%)	3	0/50 (0%)	0	0/49 (0%)	0
Musculoskeletal and connective tissue disorders
BACK PAIN	0/50 (0%)	0	1/50 (2%)	1	3/50 (6%)	3	1/50 (2%)	1	0/50 (0%)	0	1/49 (2%)	1
Nervous system disorders
HEADACHE	1/50 (2%)	1	2/50 (4%)	2	1/50 (2%)	1	3/50 (6%)	4	0/50 (0%)	0	1/49 (2%)	2
Respiratory, thoracic and mediastinal disorders
COUGH	0/50 (0%)	0	1/50 (2%)	1	1/50 (2%)	1	3/50 (6%)	3	1/50 (2%)	1	0/49 (0%)	0

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.