CONCERTO: Study to Determine the Effects of Different Doses of Methotrexate (MTX) When Taken With Adalimumab in Subjects With Early Rheumatoid Arthritis (RA)

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01185301
• Collaborator: (none)
• Enrollment: 395
• Locations: 68
• Arms: 4
• Duration (Months): 23
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the effects of different doses of methotrexate (MTX) when taken with adalimumab in subjects with early rheumatoid arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Early Rheumatoid Arthritis	Biological: adalimumab; Drug: methotrexate	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 395 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Double-Blind, Randomized, Parallel-Arm, Multicenter Study to Determine the Dose Response of Methotrexate (MTX) in Combination Therapy With Adalimumab in Subjects With Early Rheumatoid Arthritis (CONCERTO)
• Study Start Date: Oct 1, 2010
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: ADA + 2.5 mg MTX 2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	Biological: adalimumab; Pre-filled syringe every other week; Other Names: Humira ; Drug: methotrexate; weekly oral capsule dosing
Active Comparator: ADA + 5 mg MTX 5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	Biological: adalimumab; Pre-filled syringe every other week; Other Names: Humira ; Drug: methotrexate; weekly oral capsule dosing
Active Comparator: ADA + 10 mg MTX 10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	Biological: adalimumab; Pre-filled syringe every other week; Other Names: Humira ; Drug: methotrexate; weekly oral capsule dosing
Active Comparator: ADA + 20 mg MTX MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks	Biological: adalimumab; Pre-filled syringe every other week; Other Names: Humira ; Drug: methotrexate; weekly oral capsule dosing

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26 [Week 26]

   Percentage of participants achieving low disease activity as defined by a clinical response (DAS28[CRP] < 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.

Secondary Outcome Measures

1. Percentage of Participants With DAS28(CRP) Remission at Week 26 [Week 26]

   Disease remission was defined as a disease activity score, based on CRP, for 28 joints that was < 2.6 (DAS28[CRP] < 2.6). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10.

2. Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26 [Baseline, Week 26]

   Response, as defined by ACR 20 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).

3. Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26 [Baseline, Week 26]

   Response, as defined by ACR 50 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).

4. Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26 [Baseline, Week 26]

   Response, as defined by ACR 70 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).

5. Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26 [Baseline, Week 26]

   Response, as defined by ACR 90 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).

6. Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26 [Baseline, Week 26]

   Response, as defined by ACR 100 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 100% improvement in tender joint count; ≥ 100% improvement in swollen joint count; and ≥ 100% 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).

7. Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26 [Baseline, Week 26]

   The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.

8. Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ -0.22 at Week 26 [Baseline, Week 26]

   The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is a change from Baseline of ≥ 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.

9. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26 [Baseline, Week 26]

   The modified Total Sharp Score (mTSS) is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

10. Percentage of Participants With No Radiographic Progression at Week 26 [Baseline, Week 26]

    "No radiographic progression" was defined as a change from Baseline in modified Total Sharp Score (mTSS) at Week 26 of ≤ 0.5. mTSS is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

11. Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26 [Week 26]

    SDAI is a measure of disease activity derived as follows: SDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) + CRP (mg/dL), where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]), and CRP is C-reactive protein measured in mg/dL. SDAI total score = 0 to 86. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.

12. Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26 [Week 26]

    CDAI is a measure of disease activity derived as follows: CDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]). CDAI total score = 0 to 76. CDAI ≤ 2.8 indicates disease remission, > 2.8 to 10 = low disease activity, > 10 to 22 = moderate disease activity, and > 22 = high disease activity.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male and female subjects at least 18 years of age

• Subject has a diagnosis of Rheumatoid Arthritis (RA) as defined by either the 1987-revised American College of Rheumatology (ACR) classification criteria or the new ACR/ European League Against Rheumatism (EULAR) diagnostic criteria for RA 2010 and has a disease duration of less than 1 year from diagnosis by a licensed health care provider

• Subject must meet the following criteria:

1. Disease Activity Score of C-reactive Protein (DAS28[CRP]) ≥ 3.2 (at the Baseline visit only)

2. At least 6 swollen joints out of 66 assessed (at the Screening and Baseline visits)

3. At least 8 tender joints out of 68 assessed (at the Screening and Baseline visits)

4. C-reactive protein (CRP) ≥ 1.5 mg/dL (at the Screening visit only), or erythrocyte sedimentation rate (ESR) ≥ 28 mm/1h (at the Screening and Baseline visits)

5. Fulfill at least one of the following three criteria: Rheumatoid Factor (RF) positive, have at least 1 bony erosion, anti-cyclic citrullinated peptide (anti-CCP) antibody positive

• Subject is judged to be in good health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, chest x-ray (CXR), and a 12-lead electrocardiogram (ECG) performed during Screening

Exclusion Criteria:

• Subject has previous exposure to any systemic biologic therapy including adalimumab

• Subject has been previously treated with greater than 1 disease modifying antirheumatic drugs (DMARDs) or with methotrexate (MTX)

• Subject has undergone joint surgery within the preceding two months (at joints to be assessed within the study)

• Subject has chronic arthritis diagnosed before age 17 years

• History of invasive infection (e.g., listeriosis and histoplasmosis), chronic or active Hepatitis C infection, human immunodeficiency virus (HIV) infection, immunodeficiency syndrome, chronic recurring infections or active tuberculosis (TB)

• Hepatitis B virus: hepatitis B surface antigen (HBs Ag) positive (+) or detected sensitivity on the hepatitis B virus DNA (HBV DNA) polymerase chain reaction (PCR) qualitative test

• Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline visit

• Female subject who is pregnant or breast-feeding or considering becoming pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 38973	Huntsville	Alabama	United States	35801
2	Site Reference ID/Investigator# 41962	Mesa	Arizona	United States	85202
3	Site Reference ID/Investigator# 39260	Phoenix	Arizona	United States	85031
4	Site Reference ID/Investigator# 45323	Little Rock	Arkansas	United States	72205
5	Site Reference ID/Investigator# 38912	Hemet	California	United States	92543
6	Site Reference ID/Investigator# 39673	Victorville	California	United States	92395
7	Site Reference ID/Investigator# 38909	Jacksonville	Florida	United States	32209
8	Site Reference ID/Investigator# 40422	Miami	Florida	United States	33169
9	Site Reference ID/Investigator# 38910	Sarasota	Florida	United States	34239
10	Site Reference ID/Investigator# 44284	Atlanta	Georgia	United States	30312
11	Site Reference ID/Investigator# 38907	Gainesville	Georgia	United States	30501
12	Site Reference ID/Investigator# 38972	Lawrenceville	Georgia	United States	30045
13	Site Reference ID/Investigator# 39670	Rock Island	Illinois	United States	61201
14	Site Reference ID/Investigator# 42282	Springfield	Illinois	United States	62704
15	Site Reference ID/Investigator# 38911	Wichita	Kansas	United States	67203
16	Site Reference ID/Investigator# 39672	Covington	Louisiana	United States	70433
17	Site Reference ID/Investigator# 42204	Omaha	Nebraska	United States	68114
18	Site Reference ID/Investigator# 40651	Clifton	New Jersey	United States	07012
19	Site Reference ID/Investigator# 41422	Freehold	New Jersey	United States	07728
20	Site Reference ID/Investigator# 41424	Bronx	New York	United States	10467
21	Site Reference ID/Investigator# 40463	Greenville	North Carolina	United States	27834
22	Site Reference ID/Investigator# 42202	Columbus	Ohio	United States	43213
23	Site Reference ID/Investigator# 44282	Norman	Oklahoma	United States	73069
24	Site Reference ID/Investigator# 41423	Duncansville	Pennsylvania	United States	16635
25	Site Reference ID/Investigator# 38971	Charleston	South Carolina	United States	29406
26	Site Reference ID/Investigator# 39666	Jackson	Tennessee	United States	38305
27	Site Reference ID/Investigator# 39643	Dallas	Texas	United States	75231
28	Site Reference ID/Investigator# 45325	Dallas	Texas	United States	75246
29	Site Reference ID/Investigator# 52042	Houston	Texas	United States	77074
30	Site Reference ID/Investigator# 40602	Seattle	Washington	United States	98101
31	Site Reference ID/Investigator# 44924	Buenos Aires		Argentina	C1055AAF
32	Site Reference ID/Investigator# 44926	Buenos Aires		Argentina	C1425DTG
33	Site Reference ID/Investigator# 44925	Rosario, Santa Fe		Argentina	S2000PBJ
34	Site Reference ID/Investigator# 47302	San Juan		Argentina	J5402DIL
35	Site Reference ID/Investigator# 44928	Graz		Austria	80360
36	Site Reference ID/Investigator# 44930	Vienna		Austria	1090
37	Site Reference ID/Investigator# 44927	Vienna		Austria	1100
38	Site Reference ID/Investigator# 44934	Brussels		Belgium	1200
39	Site Reference ID/Investigator# 44935	Genk		Belgium	3600
40	Site Reference ID/Investigator# 44933	Gilly		Belgium	6060
41	Site Reference ID/Investigator# 44932	Liege		Belgium	4000
42	Site Reference ID/Investigator# 43783	Edmonton		Canada	T5M 0H4
43	Site Reference ID/Investigator# 43782	Winnipeg		Canada	R3A 1M3
44	Site Reference ID/Investigator# 44937	Brno		Czech Republic	63800
45	Site Reference ID/Investigator# 48962	Ceske Budejovice		Czech Republic	37021
46	Site Reference ID/Investigator# 44939	Ostrava		Czech Republic	72200
47	Site Reference ID/Investigator# 44936	Prague 2		Czech Republic	128 50
48	Site Reference ID/Investigator# 44938	Uherske Hradiste		Czech Republic	686 01
49	Site Reference ID/Investigator# 48963	Zlin		Czech Republic	76001
50	Site Reference ID/Investigator# 44945	Berlin-Buch		Germany	13125
51	Site Reference ID/Investigator# 44941	Berlin		Germany	10117
52	Site Reference ID/Investigator# 44942	Munich		Germany	80336
53	Site Reference ID/Investigator# 44944	Ratingen		Germany	40882
54	Site Reference ID/Investigator# 44943	Zerbst		Germany	39261
55	Site Reference ID/Investigator# 44946	Bydgoszcz		Poland	85168
56	Site Reference ID/Investigator# 44982	Lodz		Poland	90-242
57	Site Reference ID/Investigator# 46584	Torun		Poland	87-100
58	Site Reference ID/Investigator# 44984	Warsaw		Poland	02-118
59	Site Reference ID/Investigator# 44983	Warsaw		Poland	02-256
60	Site Reference ID/Investigator# 38975	Caguas		Puerto Rico	00725
61	Site Reference ID/Investigator# 40122	San Juan		Puerto Rico	00906-6312
62	Site Reference ID/Investigator# 39693	San Juan		Puerto Rico	00936-5067
63	Site Reference ID/Investigator# 38916	San Juan		Puerto Rico	00936-8344
64	Site Reference ID/Investigator# 39692	Vega Baja		Puerto Rico	00693
65	Site Reference ID/Investigator# 44947	A Coruna		Spain	15006
66	Site Reference ID/Investigator# 44987	Elche (Alicante)		Spain	03203
67	Site Reference ID/Investigator# 44948	Oviedo (Asturias)		Spain	33006
68	Site Reference ID/Investigator# 47782	Valencia		Spain	46026

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Dawn Carlson, MD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01185301
• Other Study ID Numbers: M12-073; 2010-019514-24
• First Posted: Aug 19, 2010
• Last Update Posted: Nov 15, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by AbbVie (prior sponsor, Abbott): Arthritis; Erosion; Humira; Adalimumab; Injection; Rheumatoid; Methotrexate
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab; Methotrexate

Study Results

Participant Flow

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Period Title: Overall Study
STARTED	98	100	99	98
COMPLETED	83	93	93	89
NOT COMPLETED	15	7	6	9

Baseline Characteristics

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX	Total
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks	Total of all reporting groups
Overall Participants	98	100	99	98	395
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.0 (13.19)	49.7 (13.14)	52.1 (12.94)	53.8 (14.41)	51.9 (13.46)
Age, Customized (participants) [Number]
< 65 years	84 85.7%	89 89%	85 85.9%	77 78.6%	335 84.8%
> 65 years	14 14.3%	11 11%	14 14.1%	21 21.4%	60 15.2%
Sex: Female, Male (Count of Participants)
Female	70 71.4%	78 78%	78 78.8%	74 75.5%	300 75.9%
Male	28 28.6%	22 22%	21 21.2%	24 24.5%	95 24.1%
28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) (scores on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [scores on a scale]	6.10 (0.921)	6.22 (0.943)	5.86 (0.971)	5.91 (1.014)	6.02 (0.970)
Modified Total Sharp Score (mTSS) (score) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score]	9.79 (12.849)	8.60 (8.912)	10.76 (13.017)	10.55 (12.852)	9.92 (12.005)
Health Assessment Questionnaire - Disability Index (HAQ-DI) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.49 (0.737)	1.57 (0.624)	1.62 (0.667)	1.58 (0.653)	1.57 (0.670)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With 28-Joint Disease Activity Score of C-reactive Protein (DAS28[CRP]) Low Disease Activity at Week 26
Description	Percentage of participants achieving low disease activity as defined by a clinical response (DAS28[CRP] < 3.2). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	42.9 43.8%	44.0 44%	56.6 57.2%	60.2 61.4%

2. Secondary Outcome

Title	Percentage of Participants With DAS28(CRP) Remission at Week 26
Description	Disease remission was defined as a disease activity score, based on CRP, for 28 joints that was < 2.6 (DAS28[CRP] < 2.6). The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	27.6 28.2%	32.0 32%	37.4 37.8%	44.9 45.8%

3. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR) 20 Criteria Response at Week 26
Description	Response, as defined by ACR 20 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	67.3 68.7%	74.0 74%	76.8 77.6%	79.6 81.2%

4. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR) 50 Criteria Response at Week 26
Description	Response, as defined by ACR 50 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	45.9 46.8%	51.0 51%	53.5 54%	62.2 63.5%

5. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR) 70 Criteria Response at Week 26
Description	Response, as defined by ACR 70 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	24.5 25%	34.0 34%	41.4 41.8%	45.9 46.8%

6. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR) 90 Criteria Response at Week 26
Description	Response, as defined by ACR 90 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 90% improvement in tender joint count; ≥ 90% improvement in swollen joint count; and ≥ 90% 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	7.1 7.2%	10.0 10%	17.2 17.4%	16.3 16.6%

7. Secondary Outcome

Title	Percentage of Participants With American College of Rheumatology (ACR) 100 Criteria Response at Week 26
Description	Response, as defined by ACR 100 criteria at Week 26. A participant is a responder if the following 3 criteria for improvement from Baseline are met: ≥ 100% improvement in tender joint count; ≥ 100% improvement in swollen joint count; and ≥ 100% 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 Disability Index of the Health Assessment Questionnaire Acute phase reactant value (C-reactive protein).
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	1.0 1%	1.0 1%	2.0 2%	4.1 4.2%

8. Secondary Outcome

Title	Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) Score at Week 26
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 very severe, high-dependency disability. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population with non-missing baseline and at least 1 non-missing post-baseline value (baseline is defined as the last non-missing value prior to the first dose of study drug); last observation carried forward.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	96	98	96	98
Mean (Standard Deviation) [units on a scale]	-0.72 (0.664)	-0.71 (0.717)	-0.78 (0.647)	-0.82 (0.698)

9. Secondary Outcome

Title	Percentage of Participants With a Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) ≤ -0.22 at Week 26
Description	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is a change from Baseline of ≥ 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI score of < 0.5. Negative change from Baseline in the overall score indicates improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	68.4 69.8%	70.0 70%	73.7 74.4%	77.6 79.2%

10. Secondary Outcome

Title	Change From Baseline in Modified Total Sharp Score (mTSS) at Week 26
Description	The modified Total Sharp Score (mTSS) is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population with available data at time point (observed cases).

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	88	94	95	90
Mean (Standard Deviation) [score on a scale]	0.9 (5.62)	0.3 (1.92)	0.4 (3.17)	0.2 (2.22)

11. Secondary Outcome

Title	Percentage of Participants With No Radiographic Progression at Week 26
Description	"No radiographic progression" was defined as a change from Baseline in modified Total Sharp Score (mTSS) at Week 26 of ≤ 0.5. mTSS is a measure of change in joint health from digitized images of radiographs of hands and feet. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	64.3 65.6%	72.0 72%	76.8 77.6%	77.6 79.2%

12. Secondary Outcome

Title	Percentage of Participants With Simplified Disease Activity Index (SDAI) Remission at Week 26
Description	SDAI is a measure of disease activity derived as follows: SDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) + CRP (mg/dL), where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]), and CRP is C-reactive protein measured in mg/dL. SDAI total score = 0 to 86. SDAI ≤ 3.3 indicates disease remission, > 3.4 to 11 = low disease activity, > 11 to 26 = moderate disease activity, and > 26 = high disease activity.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	11.2 11.4%	22.0 22%	28.3 28.6%	29.6 30.2%

13. Secondary Outcome

Title	Percentage of Participants With Clinical Disease Activity Index (CDAI) Remission at Week 26
Description	CDAI is a measure of disease activity derived as follows: CDAI = SJC28 + TJC28 + GH (cm) + PhGA (cm) where TJC28 and SJC28 represent total tender joint count and total swollen joint count, respectively, based on 28 joints (including the left and right side of the body), GH = Patient's Global Assessment of Disease Activity, and PhGA = Physician's Global Assessment of Disease Activity (both measured on a visual analogue scale with a range of 0 [none] to 10 [severe]). CDAI total score = 0 to 76. CDAI ≤ 2.8 indicates disease remission, > 2.8 to 10 = low disease activity, > 10 to 22 = moderate disease activity, and > 22 = high disease activity.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Intent-to-Treat population; participants with a missing response were imputed as non-responders.

Arm/Group Title	ADA + 2.5 mg MTX	ADA + 5 mg MTX	ADA + 10 mg MTX	ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks	5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks	MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
Measure Participants	98	100	99	98
Number [percentage of participants]	12.2 12.4%	22.0 22%	29.3 29.6%	27.6 28.2%

Adverse Events

Time Frame	Treatment-emergent adverse events and serious adverse events, defined as those that began after the first dose of study drug, but within 70 days after the last dose of study drug. Duration of treatment was 24 weeks for ADA and 25 weeks for MTX.
Arm/Group Title	ADA + 2.5 mg MTX		ADA + 5 mg MTX		ADA + 10 mg MTX		ADA + 20 mg MTX
Arm/Group Description	2.5 mg methotrexate (MTX) oral capsule weekly with 40 mg adalimumab (ADA) subcutaneous (SC) injection every other week (EOW) for 26 weeks		5 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks		10 mg MTX oral capsule weekly with 40 mg ADA SC injection EOW for 26 weeks		MTX oral capsule dose escalation from 10 mg to 20 mg in 2.5 mg increments every other week (10 mg x 2 weeks, 12.5 mg x 2 weeks, 15 mg x 2 weeks, 17.5 mg x 2 weeks), then 20 mg for 18 weeks with 40 mg ADA SC injection EOW for 26 weeks
All Cause Mortality
	ADA + 2.5 mg MTX		ADA + 5 mg MTX		ADA + 10 mg MTX		ADA + 20 mg MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	ADA + 2.5 mg MTX		ADA + 5 mg MTX		ADA + 10 mg MTX		ADA + 20 mg MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/98 (5.1%)		2/100 (2%)		3/99 (3%)		7/98 (7.1%)
Blood and lymphatic system disorders
ANAEMIA	0/98 (0%)		0/100 (0%)		1/99 (1%)		1/98 (1%)
Cardiac disorders
ACUTE CORONARY SYNDROME	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
COLITIS ULCERATIVE	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
INGUINAL HERNIA	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
General disorders
ASTHENIA	1/98 (1%)		0/100 (0%)		0/99 (0%)		0/98 (0%)
CHEST PAIN	0/98 (0%)		0/100 (0%)		1/99 (1%)		0/98 (0%)
Infections and infestations
APPENDICITIS	0/98 (0%)		1/100 (1%)		0/99 (0%)		0/98 (0%)
SEPSIS	0/98 (0%)		1/100 (1%)		0/99 (0%)		0/98 (0%)
Musculoskeletal and connective tissue disorders
INTERVERTEBRAL DISC DEGENERATION	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
OSTEOARTHRITIS	1/98 (1%)		0/100 (0%)		0/99 (0%)		0/98 (0%)
RHEUMATOID ARTHRITIS	3/98 (3.1%)		0/100 (0%)		1/99 (1%)		0/98 (0%)
Vascular disorders
HYPERTENSION	0/98 (0%)		0/100 (0%)		0/99 (0%)		1/98 (1%)
Other (Not Including Serious) Adverse Events
	ADA + 2.5 mg MTX		ADA + 5 mg MTX		ADA + 10 mg MTX		ADA + 20 mg MTX
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/98 (24.5%)		26/100 (26%)		34/99 (34.3%)		41/98 (41.8%)
Gastrointestinal disorders
ABDOMINAL PAIN	0/98 (0%)		0/100 (0%)		1/99 (1%)		5/98 (5.1%)
ABDOMINAL PAIN UPPER	4/98 (4.1%)		5/100 (5%)		4/99 (4%)		4/98 (4.1%)
DIARRHOEA	3/98 (3.1%)		6/100 (6%)		6/99 (6.1%)		3/98 (3.1%)
NAUSEA	7/98 (7.1%)		5/100 (5%)		13/99 (13.1%)		8/98 (8.2%)
General disorders
FATIGUE	2/98 (2%)		2/100 (2%)		6/99 (6.1%)		4/98 (4.1%)
Infections and infestations
NASOPHARYNGITIS	3/98 (3.1%)		6/100 (6%)		6/99 (6.1%)		11/98 (11.2%)
UPPER RESPIRATORY TRACT INFECTION	2/98 (2%)		2/100 (2%)		3/99 (3%)		5/98 (5.1%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	6/98 (6.1%)		2/100 (2%)		3/99 (3%)		0/98 (0%)
Nervous system disorders
DIZZINESS	4/98 (4.1%)		0/100 (0%)		6/99 (6.1%)		4/98 (4.1%)
HEADACHE	4/98 (4.1%)		6/100 (6%)		5/99 (5.1%)		9/98 (9.2%)
Skin and subcutaneous tissue disorders
ALOPECIA	1/98 (1%)		5/100 (5%)		6/99 (6.1%)		8/98 (8.2%)

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.