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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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:
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
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)
Hide 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.
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
Hide 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
Hide 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
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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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)
Hide 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
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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
Hide 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
Hide Outcome Measure Data
Hide 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)
Hide 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
Hide 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]
Hide 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]
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
Hide 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   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Hide 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
Hide 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
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
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Name/Title: Global Medical Services
Organization: Abbott
Phone: 1-800-633-9110
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
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