Study of the Optimal Protocol for Methotrexate and Adalimumab Combination Therapy in Early Rheumatoid Arthritis (OPTIMA)

• ClinicalTrials.gov Identifier: NCT00420927
• Recruitment Status: Completed
• First Posted: January 11, 2007
• Results First Posted: September 29, 2011
• Last Update Posted: April 18, 2012
• Sponsor: Abbott
• Information provided by (Responsible Party): Abbott

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Rheumatoid Arthritis
• Interventions: Biological: adalimumab; Drug: methotrexate; Biological: placebo
• Enrollment: 1032

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	ADA+MTX	PBO+MTX	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1	Methotrexate (MTX) monotherapy plus blinded placebo during Period 1	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Period Title: Period 1
Started	515	517	0 [1]	0 [1]	0 [1]	0 [1]	0 [1]
Completed	466	460	0	0	0	0	0
Not Completed	49	57	0	0	0	0	0
Reason Not Completed
Adverse Event	19	15	0	0	0	0	0
Withdrawal by Subject	7	12	0	0	0	0	0
Lost to Follow-up	8	6	0	0	0	0	0
Lack of efficacy/Loss of efficacy	1	6	0	0	0	0	0
Death	2	0	0	0	0	0	0
Subject moved/relocated	0	2	0	0	0	0	0
Noncompliant with study drug	1	1	0	0	0	0	0
Randomization error	1	0	0	0	0	0	0
Suspected tuberculosis/positive test	1	1	0	0	0	0	0
Study site closure	0	1	0	0	0	0	0
Subject received new diagnosis	0	2	0	0	0	0	0
Received wrong treatment/incorrect dose	0	1	0	0	0	0	0
Failed to meet entry criteria	8	7	0	0	0	0	0
Took prohibited medication	1	3	0	0	0	0	0
[1] This treatment group is not relevant to Period 1.
Period Title: Period 2
Started	0 [1]	0 [1]	102	105	259	112	348
Completed	0	0	89	95	216	97	295
Not Completed	0	0	13	10	43	15	53
Reason Not Completed
Adverse Event	0	0	7	3	17	6	20
Withdrawal by Subject	0	0	1	3	11	2	12
Lost to Follow-up	0	0	2	2	6	3	9
Lack of efficacy/Loss of efficacy	0	0	2	1	6	2	6
Received wrong treatment/incorrect dose	0	0	0	0	0	0	1
Subject unable to find transportation	0	0	0	0	0	0	1
Physician Decision	0	0	0	0	1	1	0
Sponsor decision	0	0	1	0	0	0	1
Randomization error	0	0	0	0	1	1	0
Noncompliant with study drug	0	0	0	1	0	0	2
Methotrexate intolerance	0	0	0	0	0	0	1
Took prohibited medication	0	0	0	0	1	0	0
[1] This treatment group is not relevant to Period 2.

Baseline Characteristics

Arm/Group Title		ADA+MTX	PBO+MTX	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)	Total
Arm/Group Description		Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1	Methotrexate (MTX) monotherapy plus blinded placebo(PBO) during Period 1	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2	Total of all reporting groups
Overall Number of Baseline Participants		515	517	0	0	0	0	0	1032
Baseline Analysis Population Description		[Not Specified]
Age Categorical; Measure Type: Number; Unit of measure: Participants	Number Analyzed	515 participants	517 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1032 participants
<=18 years		0	0						0
Between 18 and 65 years		418	431						849
>=65 years		97	86						183
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	515 participants	517 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1032 participants
		50.7 (14.48)	50.4 (13.62)						50.6 (14.05)
Gender; Measure Type: Number; Unit of measure: Participants	Number Analyzed	515 participants	517 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1032 participants
Female		380	382						762
Male		135	135						270
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	515 participants	517 participants	0 participants	0 participants	0 participants	0 participants	0 participants	1032 participants
Argentina		32	29						61
Australia		5	8						13
Austria		11	12						23
Belgium		41	40						81
Canada		57	58						115
Czech Republic		22	19						41
France		4	8						12
Germany		43	41						84
Hungary		8	10						18
Mexico		26	27						53
Netherlands		0	3						3
New Zealand		3	3						6
Norway		4	5						9
Poland		12	9						21
Slovakia		6	3						9
South Africa		31	32						63
Spain		25	30						55
Sweden		10	11						21
United Kingdom		26	17						43
United States		149	152						301

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 4
Description	The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

The analysis was performed on the ITT Population comprised of all subjects who entered Period 2 and received at least 1 dose of study drug (blinded or open-label) during Period 2. Nonresponder imputation was used for missing data.

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	59	73	94	61	129

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.023
	Comments	[Not Specified]
	Method	Chi-squared
	Comments	P value is from Pearson's chi-square test.

2. Secondary Outcome

Title	Number of Subjects With Low Disease Activity (DAS28 Less Than 3.2) and No Radiographic Progression From Baseline (Change in mTSS Less Than or Equal to 0.5) at Week 78, Arm 2 vs. Arm 1
Description	The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07, with scores below 3.2 indicating low disease activity. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	59	73	94	61	129

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.082
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

3. Secondary Outcome

Title	Number of Subjects With DAS28 Low Disease Activity (DAS28 Less Than 3.2) at Week 78
Description	The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, Nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	71	80	108	78	185

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.280
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.287
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

4. Secondary Outcome

Title	Number of Subjects With DAS28 Remission (DAS28 Less Than 2.6) at Week 78
Description	The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	57	77	71	66	138

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.026
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.009
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

5. Secondary Outcome

Title	Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS Less Than or Equal to 0.5) at Week 78
Description	For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448. 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	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	102	259	112	348
Measure Type: Number; Unit of Measure: Participants
	70	84	182	77	220

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.060
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.063
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

6. Secondary Outcome

Title	Number of Subjects Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 78
Description	Subjects were responders if they had greater than or equal to 20% improvement in tender joint count; greater than or equal to 20% improvement in swollen joint count; and greater than or equal to 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant (C-reactive protein).
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	84	89	172	90	257

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.395
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.640
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

7. Secondary Outcome

Title	Number of Subjects Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 78
Description	Subjects were responders if they had: greater than or equal to 50% improvement in tender joint count; greater than or equal to 50% improvement in swollen joint count; and greater than or equal to 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant (C-reactive protein).
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	72	82	120	78	198

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.159
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.217
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

8. Secondary Outcome

Title	Number of Subjects Meeting American College of Rheumatology 70% (ACR70) Response Criteria at Week 78
Description	Subjects were responders if they had: greater than or equal to 70% improvement in tender joint count; greater than or equal to 70% improvement in swollen joint count; and greater than or equal to 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant (C-reactive protein).
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

ITT Population, nonresponder imputation

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	57	73	78	64	137

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.060
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.043
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

9. Secondary Outcome

Title	Change From Baseline in DAS28 Score at Week 78
Description	The Disease Activity Score (DAS28) is calculated using the number of tender and swollen joints (out of 28 counted), C-reactive protein level, and the patient's global assessment of disease activity. The calculated range of DAS28 is 0.49 to 9.07. A DAS28 less than 2.6 indicates clinical remission, DAS28 2.6 to 3.2 indicates low disease activity, DAS28 3.2 to less than 5.1 indicates moderate disease activity, and DAS28 of 5.1 or greater indicates high disease activity.
Time Frame	Baseline to Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-3.54 (1.259)	-3.71 (1.134)	-2.70 (1.531)	-3.04 (1.513)	-3.07 (1.486)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.049
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

10. Secondary Outcome

Title	Number of Subjects With Clinical Disease Activity Index (CDAI) Low Disease Activity (CDAI Less Than or Equal to 10) at Week 78
Description	The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	75	84	109	82	195

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.240
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.271
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

11. Secondary Outcome

Title	Number of Subjects With Simplified Disease Activity Index (SDAI) Low Disease Activity (SDAI Less Than or Equal to 11) at Week 78
Description	The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	73	79	106	76	192

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.230
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.550
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

12. Secondary Outcome

Title	Number of Subjects With Clinical Disease Activity Index (CDAI) Remission (CDAI Less Than or Equal to 2.8) at Week 78
Description	The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	47	58	39	54	94

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.301
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.188
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

13. Secondary Outcome

Title	Number of Subjects With Simplified Disease Activity Index (SDAI) Remission (SDAI Less Than or Equal to 3.3) at Week 78
Description	The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	45	55	39	51	92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.314
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.235
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

14. Secondary Outcome

Title	Change From Baseline in CDAI Score at Week 78
Description	The CDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, and physician's global assessment of disease activity. Scores range from 0 to 76.0, with a higher score reflecting worsening disease.
Time Frame	Baseline to Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-33.30 (12.808)	-33.29 (12.964)	-29.06 (16.561)	-27.63 (15.526)	-31.30 (14.769)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.030
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.403
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

15. Secondary Outcome

Title	Change From Baseline in SDAI Score at Week 78
Description	The SDAI is calculated using number of swollen joints (28 joints assessed), number of tender joints (28 joints assessed), patient's global assessment of disease activity, physician's global assessment of disease activity, and acute phase reactant (C-reactive protein). Scores range from 0.1 to 86.0, with a higher score reflecting worsening disease.
Time Frame	Baseline to Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	-35.61 (13.527)	-35.16 (13.784)	-31.00 (17.856)	-29.30 (17.120)	-33.43 (15.852)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.036
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.349
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

16. Secondary Outcome

Title	Change From Baseline in Synovitis Score According to the Rheumatoid Arthritis Magnetic Resonance Imaging (RA MRI) Scoring System (RAMRIS) at Week 78
Description	Synovitis was assessed using high-field magnetic resonance imaging (MRI) of the hand and wrist. Images were read and scored according to the Outcomes Measures in Rheumatology Clinical Trials' Rheumatoid Arthritis MRI Scoring System (OMERACT RAMRIS). Synovitis in the wrist and finger joints in the most affected hand was scored from 0 (normal) to 3 (severe), for a maximum total score of 21.
Time Frame	Baseline to Week 78

Outcome Measure Data

Analysis Population Description

The analysis is based on the Primary Analysis Set, a subset of the ITT Analysis Set that includes subjects who participated in the 78-week HF MRI substudy and whose Baseline HF MRI data were collected on or before the first study drug dose. Observed scores are used in the analysis.

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	2	4	14	4	13
Mean (Standard Deviation); Unit of Measure: Scores on a scale
	2.00 (2.121)	-3.38 (2.562)	-3.25 (3.631)	-3.88 (3.351)	-4.27 (4.211)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.037
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	Analysis of covariance adjusting for baseline

17. Secondary Outcome

Title	Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5) and Normal Function (HAQ-DI Less Than 0.5) at Week 78
Description	In the Health Assessment Questionnaire Disability Index (HAQ-DI), participants rated their ability to perform daily tasks on a scale of 0 (without any difficulty) to 3 (unable to do). A mean score of 0-1 represents mild to moderate functional disability, 1-2 represents moderate to severe, 2-3 severe to very severe disability. For the modified Total Sharp score (mTSS), x-rays of hand/wrist and feet joints are scored for erosions (0 to 5) and joint space narrowing (0 to 4). The erosion score and the narrowing score are added to determine the total score, which ranges from 0 (no damage) to 448.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	49	59	65	53	84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.192
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.241
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

18. Secondary Outcome

Title	Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than or Equal to 0.5), and ACR70 Response at Week 78
Description	In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (worst joint damage). American College of Rheumatology 70% (ACR70) response indicates at least 70% improvement in tender and swollen joint counts and at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; HAQ-DI; and C-reactive protein.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	37	56	40	43	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.028
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.014
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

19. Secondary Outcome

Title	Number of Subjects With No Radiographic Progression (Change From Baseline in mTSS of Less Than or Equal to 0.5), Normal Function (HAQ-DI Less Than 0.5), and DAS28 Remission (DAS28 Less Than 2.6) at Week 78
Description	In the Health Assessment Questionnaire Disability Index (HAQ-DI), a score of 0-1 represents mild to moderate, 1-2 moderate to severe, 2-3 severe to very severe disability. The modified Total Sharp score (mTSS) ranges from 0 (no joint damage) to 448 (severe joint damage). The Disease Activity Score (DAS28) ranges from 0.49 to 9.07, with scores less than 2.6 indicating clinical remission.
Time Frame	Week 78

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)
Arm/Group Description:	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA)during Period 1, MTX monotherapy plus blinded placebo (PBO) during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1 and Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1, open-label combination therapy with ADA and MTX during Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1 and Period 2	Methotrexate (MTX) monotherapy plus blinded placebo (PBO) during Period 1, open-label combination therapy with adalimumab (ADA) and MTX during Period 2
Overall Number of Participants Analyzed	102	105	259	112	348
Measure Type: Number; Unit of Measure: Participants
	39	53	38	43	63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/ADA+MTX (Arm 2), PBO+MTX/PBO+MTX (Arm 4)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.074
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ADA+MTX/PBO+MTX (Arm 1), ADA+MTX/ADA+MTX (Arm 2)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.077
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events reported during Period 1 (Weeks 0 to 26) are presented by Period 1 treatment group. Adverse events reported during Period 2 (Weeks 26 to 78) are presented by Period 2 treatment arm (Arm 1 through Arm 5).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)	Period 1 ADA+MTX	Period 1 PBO+MTX
Arm/Group Description	Blinded combination ADA+MTX therapy during Period 1 and blinded MTX monotherapy during Period 2	Blinded combination ADA+MTX therapy during Period 1 and Period 2	Blinded combination therapy during Period 1, open-label combination therapy during Period 2	Blinded MTX monotherapy during Period 1 and Period 2	Blinded MTX monotherapy during Period 1, open-label combination therapy during Period 2	Combination therapy with methotrexate (MTX) and blinded adalimumab (ADA) during Period 1	Combination therapy with methotrexate (MTX) and blinded placebo (PBO) during Period 1
All-Cause Mortality
	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)	Period 1 ADA+MTX	Period 1 PBO+MTX
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--	--/--	--/--	--/--
Serious Adverse Events
	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)	Period 1 ADA+MTX	Period 1 PBO+MTX
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	11/102 (10.78%)	12/105 (11.43%)	18/259 (6.95%)	9/112 (8.04%)	32/348 (9.20%)	37/515 (7.18%)	32/517 (6.19%)
Cardiac disorders
Acute myocardial infarction * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Angina unstable * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Atrial fibrillation * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	1/517 (0.19%)
Bradycardia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Cardiac failure * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Cardiac failure congestive * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	1/517 (0.19%)
Coronary artery disease * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	2/515 (0.39%)	0/517 (0.00%)
Coronary artery insufficiency * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Myocardial infarction * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Right ventricular failure * 1 [1]	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Sinus bradycardia * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Supraventricular tachycardia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Congenital, familial and genetic disorders
Microgenia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Ear and labyrinth disorders
Cerumen impaction * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Vertigo * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Eye disorders
Cataract * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Gastrointestinal disorders
Abdominal hernia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Abdominal pain * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Colitis ulcerative * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Diarrhoea * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Duodenal ulcer * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Gastric dilatation * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Gastric ulcer * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	2/517 (0.39%)
Gastritis haemorrhagic * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Gastrointestinal haemorrhage * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Haemorrhoids * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Intestinal perforation * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Nausea * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Oedematous pancreatitis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Oesophageal achalasia * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Oesophageal ulcer * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Vomiting * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
General disorders
Death * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Drug intolerance * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	1/517 (0.19%)
Medical device complication * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Pyrexia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Sudden death * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Hepatobiliary disorders
Cholecystitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Cholelithiasis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Ischaemic hepatitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Infections and infestations
Atypical mycobacterial infection * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Bronchitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Bronchopneumonia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Bronchopulmonary aspergillosis * 1 [1]	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Candida sepsis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Cellulitis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	2/515 (0.39%)	1/517 (0.19%)
Diverticulitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Enterocolitis infectious * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Erysipelas * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Gangrene * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Gastroenteritis * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Herpes zoster * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Infection * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Influenza * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Lobar pneumonia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Lower respiratory tract infection * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Lower respiratory tract infection bacterial * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Orchitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Osteomyelitis * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Peritoneal tuberculosis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Pharyngitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Pneumonia * 1 [2]	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	2/348 (0.57%)	4/515 (0.78%)	1/517 (0.19%)
Pneumonia bacterial * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Pneumonia legionella * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Pulmonary tuberculosis * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	2/348 (0.57%)	0/515 (0.00%)	0/517 (0.00%)
Respiratory tract infection * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Sepsis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Sinusitis * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Staphylococcal abscess * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Staphylococcal infection * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Staphylococcal sepsis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Urinary tract infection * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Viral infection * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Vulvovaginitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Injury, poisoning and procedural complications
Femur fracture * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Forearm fracture * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Hip fracture * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Intentional overdose * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Kidney rupture * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Overdose * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Rib fracture * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Thoracic vertebral fracture * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Upper limb fracture * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Vaccination complication * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Wrist fracture * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Metabolism and nutrition disorders
Gout * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Hypoglycaemia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Malnutrition * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Musculoskeletal and connective tissue disorders
Arthralgia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	1/517 (0.19%)
Back pain * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Intervertebral disc protrusion * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	1/517 (0.19%)
Knee deformity * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Monarthritis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Osteoarthritis * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	2/517 (0.39%)
Osteoporotic fracture * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Polyarthritis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Rheumatoid arthritis * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	4/348 (1.15%)	1/515 (0.19%)	2/517 (0.39%)
Synovitis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	2/348 (0.57%)	0/515 (0.00%)	0/517 (0.00%)
Benign mediastinal neoplasm * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Bile duct cancer * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Breast cancer * 1	0/102 (0.00%)	0/105 (0.00%)	2/259 (0.77%)	1/112 (0.89%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Lung neoplasm malignant * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Oesophageal squamous cell carcinoma * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Nervous system disorders
Carotid artery aneurysm * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Cerebrovascular accident * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Dizziness * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Facial palsy * 1 [3]	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Headache * 1	1/102 (0.98%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Syncope * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	1/517 (0.19%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Psychiatric disorders
Acute stress disorder * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Confusional state * 1 [4]	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Suicide attempt * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Renal and urinary disorders
Nephrolithiasis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Renal failure acute * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Ureteric obstruction * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Reproductive system and breast disorders
Benign prostatic hyperplasia * 1	0/102 (0.00%)	2/105 (1.90%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Cervical dysplasia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Metrorrhagia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Micromastia * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Prostatitis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Uterine prolapse * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome * 1 [1]	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Alveolitis allergic * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	2/515 (0.39%)	0/517 (0.00%)
Asthma * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Chronic obstructive pulmonary disease * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Emphysema * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Haemothorax * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Interstitial lung disease * 1 [5]	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	2/348 (0.57%)	2/515 (0.39%)	0/517 (0.00%)
Pleural effusion * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	1/515 (0.19%)	0/517 (0.00%)
Pneumonitis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	2/515 (0.39%)	1/517 (0.19%)
Pulmonary embolism * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Pulmonary fibrosis * 1	0/102 (0.00%)	1/105 (0.95%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Respiratory failure * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	1/517 (0.19%)
Skin and subcutaneous tissue disorders
Dermatitis allergic * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Social circumstances
Physical abuse * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	1/348 (0.29%)	0/515 (0.00%)	0/517 (0.00%)
Surgical and medical procedures
Abortion induced * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	1/112 (0.89%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Vascular disorders
Aortic stenosis * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
Deep vein thrombosis * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Hypertension * 1	0/102 (0.00%)	0/105 (0.00%)	1/259 (0.39%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	0/517 (0.00%)
Thrombophlebitis superficial * 1	0/102 (0.00%)	0/105 (0.00%)	0/259 (0.00%)	0/112 (0.00%)	0/348 (0.00%)	0/515 (0.00%)	1/517 (0.19%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.0; [1] Adverse event resulted in death of subject; [2] Adverse event resulted in death of 1 subject in Arm 5; [3] Adverse event resulted in death of subject, who also had a fatal adverse event of confusional state (cause of death possibly cerebrovascular accident); [4] Adverse event resulted in death of subject, who also had a fatal adverse event of facial palsy (cause of death possibly cerebrovascular accident); [5] Adverse event resulted in death of 2 subjects in ADA+MTX group during Period 1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	ADA+MTX/PBO+MTX (Arm 1)	ADA+MTX/ADA+MTX (Arm 2)	ADA+MTX/OL ADA+MTX (Arm 3)	PBO+MTX/PBO+MTX (Arm 4)	PBO+MTX/OL ADA+MTX (Arm 5)	Period 1 ADA+MTX	Period 1 PBO+MTX
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	28/102 (27.45%)	38/105 (36.19%)	106/259 (40.93%)	44/112 (39.29%)	134/348 (38.51%)	149/515 (28.93%)	128/517 (24.76%)
Gastrointestinal disorders
Diarrhoea * 1	1/102 (0.98%)	1/105 (0.95%)	10/259 (3.86%)	1/112 (0.89%)	15/348 (4.31%)	23/515 (4.47%)	27/517 (5.22%)
Nausea * 1	7/102 (6.86%)	4/105 (3.81%)	15/259 (5.79%)	9/112 (8.04%)	27/348 (7.76%)	60/515 (11.65%)	55/517 (10.64%)
Infections and infestations
Bronchitis * 1	3/102 (2.94%)	2/105 (1.90%)	14/259 (5.41%)	6/112 (5.36%)	19/348 (5.46%)	16/515 (3.11%)	20/517 (3.87%)
Influenza * 1	3/102 (2.94%)	6/105 (5.71%)	9/259 (3.47%)	3/112 (2.68%)	11/348 (3.16%)	22/515 (4.27%)	12/517 (2.32%)
Nasopharyngitis * 1	5/102 (4.90%)	6/105 (5.71%)	23/259 (8.88%)	4/112 (3.57%)	23/348 (6.61%)	34/515 (6.60%)	25/517 (4.84%)
Sinusitis * 1	3/102 (2.94%)	2/105 (1.90%)	9/259 (3.47%)	8/112 (7.14%)	19/348 (5.46%)	13/515 (2.52%)	15/517 (2.90%)
Upper respiratory tract infection * 1	5/102 (4.90%)	5/105 (4.76%)	29/259 (11.20%)	7/112 (6.25%)	27/348 (7.76%)	35/515 (6.80%)	38/517 (7.35%)
Urinary tract infection * 1	2/102 (1.96%)	5/105 (4.76%)	12/259 (4.63%)	5/112 (4.46%)	22/348 (6.32%)	25/515 (4.85%)	22/517 (4.26%)
Investigations
Alanine aminotransferase increased * 1	5/102 (4.90%)	4/105 (3.81%)	16/259 (6.18%)	3/112 (2.68%)	16/348 (4.60%)	11/515 (2.14%)	14/517 (2.71%)
Nervous system disorders
Headache * 1	2/102 (1.96%)	3/105 (2.86%)	9/259 (3.47%)	2/112 (1.79%)	10/348 (2.87%)	26/515 (5.05%)	24/517 (4.64%)
Respiratory, thoracic and mediastinal disorders
Cough * 1	3/102 (2.94%)	7/105 (6.67%)	13/259 (5.02%)	4/112 (3.57%)	14/348 (4.02%)	20/515 (3.88%)	18/517 (3.48%)
Vascular disorders
Hypertension * 1	1/102 (0.98%)	5/105 (4.76%)	6/259 (2.32%)	6/112 (5.36%)	7/348 (2.01%)	18/515 (3.50%)	19/517 (3.68%)
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 13.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Any investigator or institution that plans on presenting/publishing results disclosure, should provide written notification to Abbott within 60 days of their presentation/publication. Abbott requests that no presentation/publication will be allowed until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay of any proposed presentation/publication maybe requested if Abbott needs to secure patent or other proprietary protection.

Results Point of Contact

• Name/Title: Global Medical Services
• Organization: Abbott
• Phone: 1-800-633-9110

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.

Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018 Nov;77(11):1566-1572. doi: 10.1136/annrheumdis-2018-213502. Epub 2018 Aug 3.

Kavanaugh A, van Vollenhoven RF, Fleischmann R, Emery P, Sainsbury I, Florentinus S, Chen S, Guerette B, Kupper H, Smolen JS. Testing treat-to-target outcomes with initial methotrexate monotherapy compared with initial tumour necrosis factor inhibitor (adalimumab) plus methotrexate in early rheumatoid arthritis. Ann Rheum Dis. 2018 Feb;77(2):289-292. doi: 10.1136/annrheumdis-2017-211871. Epub 2017 Nov 16.

Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.

Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.

Smolen JS, Emery P, Fleischmann R, van Vollenhoven RF, Pavelka K, Durez P, Guerette B, Kupper H, Redden L, Arora V, Kavanaugh A. Adjustment of therapy in rheumatoid arthritis on the basis of achievement of stable low disease activity with adalimumab plus methotrexate or methotrexate alone: the randomised controlled OPTIMA trial. Lancet. 2014 Jan 25;383(9914):321-32. doi: 10.1016/S0140-6736(13)61751-1. Epub 2013 Oct 26. Erratum In: Lancet. 2014 Jan 25;383(9914):308.

• Responsible Party: Abbott
• ClinicalTrials.gov Identifier: NCT00420927
• Other Study ID Numbers: M06-810; 2006-004139-31 ( EudraCT Number )
• First Submitted: January 9, 2007
• First Posted: January 11, 2007
• Results First Submitted: July 1, 2011
• Results First Posted: September 29, 2011
• Last Update Posted: April 18, 2012