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Efficacy and Safety of Adalimumab in Patients With Active Rheumatoid Arthritis Treated Concomitantly With Methotrexate.

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: NCT00195702
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : March 1, 2010
Last Update Posted : August 26, 2011
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: Placebo
Enrollment 619
Recruitment Details Subjects were enrolled at 95 sites in the United States and Canada between February 2000 and August 2001.
Pre-assignment Details Eligible subjects who were taking disease-modifying anti-rheumatic drugs (DMARDs) other than methotrexate (MTX) entered a 4- to 6-week washout period, during which previous DMARDs (except MTX) were discontinued. Subjects who were not taking DMARDs, other than MTX, entered directly into the 52-week double-blind treatment period of the study.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew DB Adalimumab 20 mg ew/OL Adalimumab 40 mg Eow DB Adalimumab 40 mg Eow/OL Adalimumab 40 mg Eow DB Placebo ew/OL Adalimumab 40 mg Eow
Hide Arm/Group Description Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received adalimumab 20 mg weekly (ew) during the double-blind (DB) phase, then received adalimumab 40 mg every other week (eow) during the open-label (OL) extension phase. Subjects received concomitant methotrexate (MTX) during both phases of the study. Subjects received adalimumab 40 mg every other week (eow) during the double-blind (DB) phase, then received adalimumab 40 mg every other week (eow) during the open-label (OL) extension phase. Subjects received concomitant methotrexate (MTX) during both phases of the study. Subjects received placebo weekly (ew) during the double-blind (DB) phase, then received adalimumab 40 mg every other week (eow) during the open-label (OL) extension phase. Subjects received concomitant methotrexate (MTX) during both phases of the study.
Period Title: Double-blind Phase
Started 212 [1] 207 200 0 0 0
Completed 168 159 140 0 0 0
Not Completed 44 48 60 0 0 0
[1]
For all groups, started indicates when the subjects entered the 52-week double-blind phase.
Period Title: Open-label Extension Phase
Started 0 0 0 165 [1] 158 [2] 134 [3]
Completed 0 0 0 66 80 56
Not Completed 0 0 0 99 78 78
[1]
3 subjects completed the double-blind phase but did not enter the open-label extension phase.
[2]
1 subject completed the double-blind phase but did not enter the open-label extension phase.
[3]
6 subjects completed the double-blind phase but did not enter the open-label extension phase.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew Total
Hide Arm/Group Description Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase. Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase. Total of all reporting groups
Overall Number of Baseline Participants 212 207 200 619
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 212 participants 207 participants 200 participants 619 participants
< 40 years 10 27 18 55
Between 40 and 64 years 150 115 137 402
Between 65 and 74 years 41 54 35 130
>= 75 years 11 11 10 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 212 participants 207 participants 200 participants 619 participants
Female
160
  75.5%
158
  76.3%
146
  73.0%
464
  75.0%
Male
52
  24.5%
49
  23.7%
54
  27.0%
155
  25.0%
1.Primary Outcome
Title Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
129 131 59
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the ACR20 response tested first. The ACR20 response rate at Week 24 was initially assessed using Pearson's chi-squared test at a significance level of 0.05. If significant, pairwise comparisons between each adalimumab dose group and the placebo group were performed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the ACR20 response tested first. The ACR20 response rate at Week 24 was initially assessed using Pearson's chi-squared test at a significance level of 0.05. If significant, pairwise comparisons between each adalimumab dose group and the placebo group were performed.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Modified Total Sharp X-ray Score at Week 52
Hide Description Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 52. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Missing values were imputed via linear extrapolation from baseline using data collected at baseline and Week 24 or early termination.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 196 183 172
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.8  (4.9) 0.1  (4.8) 2.7  (6.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the change in modified total Sharp x-ray score at Week 52 tested second. Normality was evaluated by applying the Shapiro-Wilk test procedure to the residuals from the parametric model. The final analysis was performed following a non-parametric approach, ranking the results prior to fitting the model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments An ANCOVA model with baseline erosion scores as the covariate was performed. An overall significance test at alpha =0.05 was done. Pairwise comparisons, each at alpha =0.05 (2-sided), were performed if the overall test was significant.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the change in modified total Sharp x-ray score at Week 52 tested second. Normality was evaluated by applying the Shapiro-Wilk test procedure to the residuals from the parametric model. The final analysis was performed following a non-parametric approach, ranking the results prior to fitting the model.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments An ANCOVA model with baseline erosion scores as the covariate was performed. An overall significance test at alpha =0.05 was done. Pairwise comparisons, each at alpha =0.05 (2-sided), were performed if the overall test was significant.
Method ANCOVA
Comments [Not Specified]
3.Primary Outcome
Title Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52
Hide Description Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Last observation carried forward (LOCF) data analysis was used for missing values.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 204 198
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.61  (0.55) -0.59  (0.57) -0.25  (0.56)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the change from baseline in the HAQ at Week 52 tested last. The difference among all treatment groups was assessed using ANCOVA with the baseline value as the covariate. If this was significant (p<=0.05), pairwise comparisons between each adalimumab dose group and placebo were evaluated using the same method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Normality was evaluated by applying the Shapiro-Wilk test to residuals from the parametric model. The final analysis was performed using a parametric approach.
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
Comments The 3 primary efficacy variables were considered in a hierarchical order, with the change from baseline in the HAQ at Week 52 tested last. The difference among all treatment groups was assessed using ANCOVA with the baseline value as the covariate. If this was significant (p<=0.05), pairwise comparisons between each adalimumab dose group and placebo were evaluated using the same method.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments Normality was evaluated by applying the Shapiro-Wilk test to residuals from the parametric model. The final analysis was performed using a parametric approach.
Method ANCOVA
Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants Meeting ACR20 Response Criteria at Week 52
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
116 122 48
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Modified Total Sharp X-ray Score at Week 24
Hide Description Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 24. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Missing values were imputed via linear extrapolation from baseline using data collected at baseline and Week 52.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 196 183 172
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.6  (4.9) 0.3  (4.5) 1.3  (3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 [Not Specified]
6.Secondary Outcome
Title Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24
Hide Description Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. LOCF data analysis was used for missing values.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 204 198
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-0.60  (0.53) -0.56  (0.52) -0.24  (0.52)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 [Not Specified]
7.Secondary Outcome
Title Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24
Hide Description Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Responders had a >= 0.22-unit decrease (improvement) in HAQ scores from baseline to Week 12 or 24.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Subjects who were responders at Week 12 or 24 were evaluated to determine whether the response was maintained. LOCF data analysis was used for missing values.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
Maintained Response 130 121 73
Did Not Maintain Response 7 4 9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
8.Secondary Outcome
Title Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Subjects who were ACR20 responders at Week 24 were evaluated to determine whether the response was maintained. Observed data were analyzed.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 129 131 59
Measure Type: Number
Unit of Measure: Participants
Maintained Response 99 111 32
Did Not Maintain Response 21 12 23
Missing 9 8 4
9.Secondary Outcome
Title Number of Participants With a Continuous ACR70 Response for 6 Months During 52 Weeks of Treatment
Hide Description Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Baseline through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
20 18 3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 Chi-squared
Comments [Not Specified]
10.Secondary Outcome
Title Time to First Response According to ACR20 Criteria - Number of Participants Meeting ACR20 Criteria for the First Time at Each Time Point
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Baseline through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed. The number of subjects meeting ACR20 response criteria for the first time at each time point is presented.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
Non-responder 25 29 81
Week 2 69 53 26
Week 4 48 48 30
Week 8 29 33 21
Week 12 17 23 14
Week 16 7 8 12
Week 20 8 7 3
Week 24 2 2 7
Week 32 4 2 2
Week 40 0 2 1
Week 48 1 0 2
Week 52 2 0 1
11.Secondary Outcome
Title Time to First Response According to ACR50 Criteria - Number of Participants Meeting ACR50 Criteria for the First Time at Each Time Point
Hide Description Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Baseline through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed. The number of subjects meeting ACR50 response criteria for the first time at each time point is presented.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
Non-responder 71 69 135
Week 2 18 13 4
Week 4 17 26 6
Week 8 26 25 6
Week 12 25 21 10
Week 16 23 21 8
Week 20 16 10 9
Week 24 7 7 3
Week 32 4 7 8
Week 40 3 2 6
Week 48 1 3 3
Week 52 1 3 2
12.Secondary Outcome
Title Time to First Response According to ACR70 Criteria - Number of Participants Meeting ACR70 Criteria for the First Time at Each Time Point
Hide Description Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 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. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.
Time Frame Baseline through Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Observed data were analyzed. The number of subjects meeting ACR70 response criteria for the first time at each time point is presented.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 212 207 200
Measure Type: Number
Unit of Measure: Participants
Non-responder 126 120 177
Week 2 5 5 2
Week 4 5 6 3
Week 8 11 7 1
Week 12 14 16 2
Week 16 15 9 1
Week 20 9 11 2
Week 24 4 11 2
Week 32 9 8 3
Week 40 4 4 2
Week 48 4 6 3
Week 52 6 4 2
13.Secondary Outcome
Title Estimated Yearly Progression of Rheumatoid Arthritis
Hide Description Estimated yearly progression was defined as modified total Sharp x-ray score at baseline divided by duration of rheumatoid arthritis disease at baseline. Actual progression during the study was defined as modified total Sharp x-ray score at Week 52 minus modified total Sharp x-ray score at baseline divided by the duration of the study. The range of scores for the modified total Sharp x-ray score was 0 (normal) to 398 (maximal disease).
Time Frame Baseline and Week 52
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Hide Analysis Population Description
Full analysis set, defined as all subjects who were randomized and received at least one injection of study drug. Missing values were imputed via linear extrapolation from baseline.
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase.
Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase.
Overall Number of Participants Analyzed 200 194 184
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Estimated yearly progression 11.11  (16.75) 9.46  (10.42) 9.97  (12.84)
Actual progression during study 0.77  (4.90) 0.09  (4.75) 2.66  (6.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 20 mg ew, DB Placebo ew
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 [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection DB Adalimumab 40 mg Eow, DB Placebo ew
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 [Not Specified]
14.Other Pre-specified Outcome
Title Baseline Measure: Gender - Female/Male - for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)
Hide Description Gender (female/male) recorded at Baseline for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.
Time Frame Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group
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Hide Analysis Population Description
Participants in the Any Adalimumab Through Year 10 group are intent-to-treat subjects.
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 553
Measure Type: Number
Unit of Measure: participants
Female 413
Male 140
15.Other Pre-specified Outcome
Title Baseline Measure: Age Categories for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)
Hide Description Age recorded at Baseline, reported by category, for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.
Time Frame Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group
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Hide Analysis Population Description
Participants in the Any Adalimumab Through Year 10 group are intent-to-treat subjects.
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 553
Measure Type: Number
Unit of Measure: participants
< 40 years 50
Between 40 and 64 years 361
Between 65 and 74 years 117
>= 75 years 25
16.Other Pre-specified Outcome
Title Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed as observed (without imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 290
Measure Type: Number
Unit of Measure: Participants
200
17.Other Pre-specified Outcome
Title Number of Participants Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 520
Hide Description Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 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 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed using data as observed (without imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 148
Measure Type: Number
Unit of Measure: participants
115
18.Other Pre-specified Outcome
Title Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260
Hide Description Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 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 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 290
Measure Type: Number
Unit of Measure: participants
153
19.Other Pre-specified Outcome
Title Number of Participants Meeting the American College of Rheumatology 50% (ACR50) Response Criteria at Week 520
Hide Description Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 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 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 148
Measure Type: Number
Unit of Measure: participants
100
20.Other Pre-specified Outcome
Title Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 260
Hide Description Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 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 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 290
Measure Type: Number
Unit of Measure: participants
87
21.Other Pre-specified Outcome
Title Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 520
Hide Description Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 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 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. All analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 148
Measure Type: Number
Unit of Measure: participants
78
22.Other Pre-specified Outcome
Title Number of Participants With a Continuous American College of Rheumatology 70% (ACR70) Response for at Least 6 Months Through Year 10
Hide Description Patients were responders if they had: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=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 Baseline through Week 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response. Analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 535
Measure Type: Number
Unit of Measure: participants
159
23.Other Pre-specified Outcome
Title Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 260
Hide Description The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.
Time Frame Week 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat with non-missing response who remained in the study. Baseline was the last non-missing value prior to the first injection of adalimumab. Analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 300
Measure Type: Number
Unit of Measure: participants
205
24.Other Pre-specified Outcome
Title Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 520
Hide Description The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.
Time Frame Week 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing response who remained in the study. Baseline was the last non-missing value prior to the first injection of adalimumab. Analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 149
Measure Type: Number
Unit of Measure: participants
110
25.Other Pre-specified Outcome
Title Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260
Hide Description Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.
Time Frame Baseline and Week 260
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing change who remained in the study. Baseline was the last non-missing value prior to the first injection of adalimumab. Analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 300
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.56  (0.62)
26.Other Pre-specified Outcome
Title Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520
Hide Description Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.
Time Frame Baseline and Week 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants analyzed were intent-to-treat subjects with non-missing change who remained in the study. Baseline was the last non-missing value prior to the first injection of adalimumab. Analyses were performed using data as observed (no imputation).
Arm/Group Title Any Adalimumab Through Year 10
Hide Arm/Group Description:
Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
Overall Number of Participants Analyzed 149
Mean (Standard Deviation)
Unit of Measure: units on a scale
-0.62  (0.60)
27.Other Pre-specified Outcome
Title Change From Baseline in Modified Total Sharp X-ray Score at Week 416
Hide Description Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 416. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
Time Frame Baseline and Week 416
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in each of the three groups were randomized subjects with non-missing radiographs who remained in the study. Baseline was defined as the value at the first visit. Analyses were performed using data as observed (no imputation).
Arm/Group Title DB Adalimumab 20 mg ew/OL Adalimumab 40 mg Eow DB Adalimumab 40 mg Eow/OL Adalimumab 40 mg Eow DB Placebo ew/OL Adalimumab 40 mg Eow
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) during the double-blind (DB) phase, followed by adalimumab every other week (eow) during the open-label (OL) extension, along with concomitant methotrexate (MTX).
Subjects received adalimumab 40 mg every other week (eow) during the double-blind (DB) phase, followed by adalimumab 40 mg eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
Subjects received placebo every week (ew) during the double-blind (DB) phase, followed by adalimumab 40 mg every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
Overall Number of Participants Analyzed 70 81 53
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.16  (7.969) 0.14  (9.310) 4.83  (10.012)
28.Other Pre-specified Outcome
Title Change From Baseline in Modified Total Sharp X-ray Score at Week 520
Hide Description Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 520. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.
Time Frame Baseline and Week 520
Hide Outcome Measure Data
Hide Analysis Population Description
Participants in each of the three groups were randomized subjects with non-missing radiographs who remained in the study. Baseline was defined as the value at the first visit. Analyses were performed using data as observed (no imputation).
Arm/Group Title DB Adalimumab 20 mg ew/OL Adalimumab 40 mg Eow DB Adalimumab 40 mg Eow/OL Adalimumab 40 mg Eow DB Placebo ew/OL Adalimumab 40 mg Eow
Hide Arm/Group Description:
Subjects received adalimumab 20 mg every week (ew) during the double-blind (DB) phase, followed by adalimumab every other week (eow) during the open-label (OL) extension, along with concomitant methotrexate (MTX).
Subjects received adalimumab 40 mg every other week (eow) during the double-blind (DB) phase, followed by adalimumab 40 mg eow during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
Subjects received placebo every week (ew) during the double-blind (DB) phase, followed by adalimumab 40 mg every other week (eow) during the open-label (OL) extension phase, along with concomitant methotrexate (MTX).
Overall Number of Participants Analyzed 70 79 54
Mean (Standard Deviation)
Unit of Measure: units on a scale
2.60  (8.822) 0.72  (10.430) 6.18  (12.071)
Time Frame For the double-blind (DB) phase: Week 0 to Week 52; for the Any Adalimumab Through Year 10 (intent-to-treat [ITT]) group: first adalimumab injection to the last day in Year 10 (for each subject, the day of the last adalimumab injection plus 70 days)
Adverse Event Reporting Description The protocol specified that adverse events (AEs) be summarized by HARTS body system/preferred term (used in the clinical study report and primary publication for the DB phase). AE terms for the DB phase were recoded using MedDRA version 12.1 for purposes of this disclosure. AEs for the Any Adalimumab group were coded using MedDRA version 13.1.
 
Arm/Group Title DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew Any Adalimumab Through Year 10
Hide Arm/Group Description Subjects received adalimumab 20 mg every week (ew) and concomitant methotrexate (MTX) during the 52-week double-blind treatment phase. Subjects received adalimumab 40 mg every other week (eow) and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received placebo every week and concomitant methotrexate (MTX) during the 52-week double-blind phase. Subjects received at least 1 dose of adalimumab over the 10-year duration of the study (the intent-to-treat population, N = 553).
All-Cause Mortality
DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew Any Adalimumab Through Year 10
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew Any Adalimumab Through Year 10
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   34/212 (16.04%)   27/207 (13.04%)   20/200 (10.00%)   271/553 (49.01%) 
Blood and lymphatic system disorders         
Agranulocytosis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Lymphadenopathy † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Pancytopenia † 1  0/212 (0.00%)  2/207 (0.97%)  0/200 (0.00%)  2/553 (0.36%) 
Anaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Cardiac disorders         
Acute myocardial infarction † 1  0/212 (0.00%)  1/207 (0.48%)  2/200 (1.00%)  2/553 (0.36%) 
Atrial fibrillation † 1  1/212 (0.47%)  1/207 (0.48%)  1/200 (0.50%)  7/553 (1.27%) 
Cardiac arrest † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Cardiac failure congestive † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  5/553 (0.90%) 
Coronary artery disease † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  7/553 (1.27%) 
Mitral valve incompetence † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Myocardial infarction † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  10/553 (1.81%) 
Pericarditis † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Angina pectoris † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Angina unstable † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Aortic valve incompetence † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Aortic valve stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Arrhythmia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Atrial flutter † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Atrial tachycardia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Atrioventricular block † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Atrioventricular block complete † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Atrioventricular block second degree † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Bradycardia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cardiac failure † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cardiogenic shock † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cardiomyopathy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Coronary artery stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Left ventricular failure † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Mitral valve disease † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Sick sinus syndrome † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Silent myocardial infarction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Supraventricular tachycardia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Congenital, familial and genetic disorders         
Cardiac septal defect † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ear and labyrinth disorders         
Inner ear disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Vestibular disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Endocrine disorders         
Inappropriate antidiuretic hormone secretion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Eye disorders         
Retinal detachment † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastrointestinal disorders         
Gastrooesophageal reflux disease † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Abdominal pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Colitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Colonic polyp † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Constipation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Diarrhea † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Diverticulum † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Diverticulum intestinal haemorrhagic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Duodenitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Enterocele † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Faecal incontinence † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Faeces discoloured † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastric ulcer haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastric volvulus † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastrititis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Gastrointestinal heamorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Haematochezia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hiatus hernia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Ileus † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Inguinal hernia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intestinal infarction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intestinal ischaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intestinal obstruction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intestinal ulcer perforation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Nausea † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Oesophageal stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pancreatitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Peptic ulcer haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Rectal haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Salivary gland mass † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Small intestinal obstruction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Umbilical hernia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Upper gastrointestinal haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Vomiting † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
General disorders         
Chest pain † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  4/553 (0.72%) 
Non-cardiac chest pain † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  6/553 (1.08%) 
Pelvic mass † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Cyst rupture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Death † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Device dislocation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Multi-organ failure † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pyrexia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Sudden death † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ulcer haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hepatobiliary disorders         
Cholelithiasis † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Cholestasis † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cholecystitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  5/553 (0.90%) 
Cholecystitis chronic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Immune system disorders         
Iodine allergy † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Serum sickness † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Hypersensitivity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Infections and infestations         
Acute tonsillitis † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Bronchitis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  6/553 (1.08%) 
Diverticulitis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  4/553 (0.72%) 
Escherichia sepsis † 1  1/212 (0.47%)  1/207 (0.48%)  0/200 (0.00%)  3/553 (0.54%) 
Gastroenteritis viral † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Herpes zoster † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  2/553 (0.36%) 
Histoplasmosis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  5/553 (0.90%) 
Infected skin ulcer † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pneumonia † 1  1/212 (0.47%)  4/207 (1.93%)  1/200 (0.50%)  20/553 (3.62%) 
Pyelonephritis † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  5/553 (0.90%) 
Septic shock † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  3/553 (0.54%) 
Tuberculosis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  2/553 (0.36%) 
Urinary tract infection † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  3/553 (0.54%) 
Abscess † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Abscess limb † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Appendicitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Arthritis bacterial † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Arthritis infective † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Bacteraemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Bronchiectasis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cellulitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  15/553 (2.71%) 
Candidiasis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Enterococal infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Erysipelas † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Eye infection bacterial † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Folliculitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastroenteritis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Haematoma infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Herpes zoster ophthalmic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Histoplasmosis disseminated † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Incision site infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Liver abscess † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lobar pneumonia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  7/553 (1.27%) 
Localised infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Meningitis viral † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Necrotising fasciitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Osteomyelitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Pneumonia primary atypical † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pneumonia streptococcal † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Postoperative wound infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pyelonephritis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  5/553 (0.90%) 
Sepsis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  4/553 (0.72%) 
Sepsis syndrome † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Soft tissue infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Staphylococcal bacteraemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Staphylococcal infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Staphylococcal sepsis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Streptococcal infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Urosepsis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Pseudomonas infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Injury, poisoning and procedural complications         
Ankle fracture † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Cardiac pacemaker malfunction † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Cervical vertebral fracture † 1  0/212 (0.00%)  1/207 (0.48%)  1/200 (0.50%)  1/553 (0.18%) 
Chemical poisoning † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Femur fracture † 1  2/212 (0.94%)  1/207 (0.48%)  0/200 (0.00%)  6/553 (1.08%) 
Fibula fracture † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hip fracture † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  7/553 (1.27%) 
Joint dislocation † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  2/553 (0.36%) 
Joint dislocation postoperative † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Multiple fractures † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Pelvic fracture † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  2/553 (0.36%) 
Rib fracture † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  1/553 (0.18%) 
Subdural haematoma † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Tibia fracture † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Anastomotic ulcer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Arthropod bite † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Back injuury † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Compression fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Eye injury † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Facial bones fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Fall † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  4/553 (0.72%) 
Femoral neck fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Head injury † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Joint sprain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ligament rupture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Limb injury † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lower limb fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Lumbar vertebral fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Postoperative wound complication † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Procedural complication † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Procedural nausea † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Procedural pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Procedural vomiting † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pubis fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Road traffic accident † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Skin flap necrosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Spinal compression fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Upper limb fracture † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Vascular pseudoaneurysm † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Investigations         
Blood albumin decreased † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Blood pressure increased † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Metabolism and nutrition disorders         
Dehydration † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  6/553 (1.08%) 
Ketoacidosis † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Decreased appetite † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Fluid overload † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hypoglycaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Hypokalaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hyponatraemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  13/553 (2.35%) 
Arthropathy † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Back pain † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Haemarthrosis † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  1/553 (0.18%) 
Joint swelling † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Muscular weakness † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Polyarthritis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Rheumatoid arthritis † 1  2/212 (0.94%)  0/207 (0.00%)  1/200 (0.50%)  35/553 (6.33%) 
Spinal disorder † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Arthritis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Bursitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Flank pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Foot deformity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Fracture nonunion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hand deformity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Intervertebral disc degeneration † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intervertebral disc disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intervertebral disc protrusion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  4/553 (0.72%) 
Limb discomfort † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lumbar spinal stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Musculoskeletal pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Osteoarthritis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  18/553 (3.25%) 
Pain in extremity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Rotator cuff syndrome † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Sacroiliitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Scoliosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Spinal column stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Spondylolisthesis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Synovial cyst † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Osteonecrosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Synovitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
B-cell lymphoma † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Basal cell carcinoma † 1  1/212 (0.47%)  1/207 (0.48%)  0/200 (0.00%)  3/553 (0.54%) 
Benign breast neoplasm † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Breast cancer † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  5/553 (0.90%) 
Cardiac myxoma † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Metastases to bone † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Polycythaemia vera † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Squamous cell carcinoma † 1  1/212 (0.47%)  1/207 (0.48%)  0/200 (0.00%)  3/553 (0.54%) 
Testicular seminoma (pure) † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Cervix carcinoma stage I † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Colon adenoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Colon cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Colorectal cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Colorectal cancer metastatic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastrointestinal carcinoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hodgkin's disease † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lung adenocarcinoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lung squamous cell carcinoma stage unspecified † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lymphoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Metastases to abdominal cavity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Metastases to liver † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Metastatic gastric cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Non-Hodgkin's lymphoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Non-small cell lung cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Non-small cell lung cancer metastatic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Oesophageal adenocarcinoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ovarian adenoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ovarian cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ovarian epithelial cancer metastatic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pituitary tumour benign † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Renal cell carcinoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Skin cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Small intestine carcinoma metastatic † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Uterine cancer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Nervous system disorders         
Cerebrovascular accident † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  3/553 (0.54%) 
Multiple sclerosis † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Paraesthesia † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Tremor † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Balance disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Carotid artery occlusion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Carotid artery stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Cerebral haemorrhage † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Dizziness † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Embolic stroke † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Intracranial aneurysm † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Ischaemic cerebral infarction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lacunar infarction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Loss of consciousness † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Lumbar radiculopathy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Muscle contractions involuntary † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Presyncope † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Syncope † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  4/553 (0.72%) 
Transient ischaemic attack † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  6/553 (1.08%) 
Psychiatric disorders         
Confusional state † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  2/553 (0.36%) 
Depression † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  2/553 (0.36%) 
Bipolar disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Psychotic disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Renal and urinary disorders         
Renal vessel disorder † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Azotaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Bladder disorder † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Bladder prolapse † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Calculus urinary † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Nephrolithiasis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Renal failure † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Renal failure acute † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Stress urinary incontinence † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Urinary incontinence † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Reproductive system and breast disorders         
Postmenopausal haemorrhage † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Benign prostatic hyperplasia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Dysfunctional uterine bleeding † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Female genital tract fistula † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Menorrhagia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Pelvic prolapse † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Prostatitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Rectocele † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Uterine prolapse † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Respiratory, thoracic and mediastinal disorders         
Bronchospasm † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Chronic obstructive pulmonary disease † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  4/553 (0.72%) 
Dyspnoea † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  2/553 (0.36%) 
Lung disorder † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Pleural effusion † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  2/553 (0.36%) 
Pneumonitis † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Pulmonary embolism † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  5/553 (0.90%) 
Asthma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Emphysema † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Interstitial lung disease † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pneumonia aspiration † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pneumothorax † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pulmonary fibrosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pulmonary hypertension † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Pulmonary toxicity † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Respiratory distress † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Respiratory failure † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Skin and subcutaneous tissue disorders         
Rash † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Skin ulcer † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Decubitus ulcer † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hypoaesthesia facial † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Surgical and medical procedures         
Cholecystectomy † 1  1/212 (0.47%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hysterectomy † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Knee arthroplasty † 1  2/212 (0.94%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Skin neoplasm excision † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Toe operation † 1  0/212 (0.00%)  1/207 (0.48%)  0/200 (0.00%)  1/553 (0.18%) 
Ankle operation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Breast prosthesis implantation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Breast reconstruction † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Finger amputation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Foot operation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Gastric bypass † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hip arthroplasty † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Mastectomy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Spinal laminectomy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Vascular disorders         
Thrombosis † 1  0/212 (0.00%)  0/207 (0.00%)  1/200 (0.50%)  0/553 (0.00%) 
Angiopathy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Aortic aneurysm † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  3/553 (0.54%) 
Aortic stenosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
Deep vein thrombosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  5/553 (0.90%) 
Haematoma † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hypertensive crisis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hypertensive emergency † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  1/553 (0.18%) 
Hypotension † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  2/553 (0.36%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1 and 13.1
2
Term from vocabulary, MedDRA 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DB Adalimumab 20 mg ew DB Adalimumab 40 mg Eow DB Placebo ew Any Adalimumab Through Year 10
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   167/212 (78.77%)   148/207 (71.50%)   149/200 (74.50%)   511/553 (92.41%) 
Blood and lymphatic system disorders         
Anaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  39/553 (7.05%) 
Eye disorders         
Cataract † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  59/553 (10.67%) 
Dry eye † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  31/553 (5.61%) 
Gastrointestinal disorders         
Diarrhoea † 1  23/212 (10.85%)  20/207 (9.66%)  30/200 (15.00%)  97/553 (17.54%) 
Nausea † 1  28/212 (13.21%)  19/207 (9.18%)  25/200 (12.50%)  94/553 (17.00%) 
Vomiting † 1  6/212 (2.83%)  4/207 (1.93%)  12/200 (6.00%)  42/553 (7.59%) 
Abdominal discomfort † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  31/553 (5.61%) 
Abdominal pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  40/553 (7.23%) 
Abdominal pain upper † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  35/553 (6.33%) 
Constipation † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  47/553 (8.50%) 
Dyspepsia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  51/553 (9.22%) 
Gastrooesophageal reflux disease † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  52/553 (9.40%) 
General disorders         
Injection site pain † 1  37/212 (17.45%)  37/207 (17.87%)  43/200 (21.50%)  74/553 (13.38%) 
Oedema peripheral † 1  2/212 (0.94%)  11/207 (5.31%)  7/200 (3.50%)  76/553 (13.74%) 
Fatigue † 1  18/212 (8.49%)  11/207 (5.31%)  15/200 (7.50%)  79/553 (14.29%) 
Chest pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  42/553 (7.59%) 
Immune system disorders         
Seasonal allergy † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  33/553 (5.97%) 
Infections and infestations         
Bronchitis † 1  16/212 (7.55%)  7/207 (3.38%)  15/200 (7.50%)  106/553 (19.17%) 
Influenza † 1  10/212 (4.72%)  6/207 (2.90%)  13/200 (6.50%)  79/553 (14.29%) 
Upper respiratory tract infection † 1  35/212 (16.51%)  35/207 (16.91%)  22/200 (11.00%)  225/553 (40.69%) 
Urinary tract infection † 1  16/212 (7.55%)  18/207 (8.70%)  15/200 (7.50%)  118/553 (21.34%) 
Nasopharyngitis † 1  23/212 (10.85%)  24/207 (11.59%)  18/200 (9.00%)  119/553 (21.52%) 
Sinusitis † 1  21/212 (9.91%)  22/207 (10.63%)  17/200 (8.50%)  150/553 (27.12%) 
Ear infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  30/553 (5.42%) 
Gastroenteritis viral † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  35/553 (6.33%) 
Herpes zoster † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  50/553 (9.04%) 
Localised infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  30/553 (5.42%) 
Oral herpes † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  29/553 (5.24%) 
Pneumonia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  32/553 (5.79%) 
Tooth infection † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  29/553 (5.24%) 
Injury, poisoning and procedural complications         
Contusion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  46/553 (8.32%) 
Joint sprain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  35/553 (6.33%) 
Limb injury † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  29/553 (5.24%) 
Muscle strain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  32/553 (5.79%) 
Procedural pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  38/553 (6.87%) 
Investigations         
Alanine aminotransferase increased † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  42/553 (7.59%) 
Aspartate aminotransferase increased † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  42/553 (7.59%) 
Metabolism and nutrition disorders         
Hypercholesterolaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  48/553 (8.68%) 
Hyperlipidaemia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  29/553 (5.24%) 
Musculoskeletal and connective tissue disorders         
Arthralgia † 1  19/212 (8.96%)  11/207 (5.31%)  15/200 (7.50%)  120/553 (21.70%) 
Back pain † 1  15/212 (7.08%)  10/207 (4.83%)  9/200 (4.50%)  103/553 (18.63%) 
Pain in extremity † 1  11/212 (5.19%)  11/207 (5.31%)  8/200 (4.00%)  77/553 (13.92%) 
Muscle spasms † 1  9/212 (4.25%)  8/207 (3.86%)  10/200 (5.00%)  44/553 (7.96%) 
Rheumatoid arthritis † 1  10/212 (4.72%)  14/207 (6.76%)  24/200 (12.00%)  123/553 (22.24%) 
Bursitis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  45/553 (8.14%) 
Joint swelling † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  45/553 (8.14%) 
Musculoskeletal pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  50/553 (9.04%) 
Neck pain † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  32/553 (5.79%) 
Osteoarthritis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  32/553 (5.79%) 
Osteopenia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  35/553 (6.33%) 
Osteoporosis † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  35/553 (6.33%) 
Nervous system disorders         
Dizziness † 1  11/212 (5.19%)  7/207 (3.38%)  11/200 (5.50%)  63/553 (11.39%) 
Headache † 1  28/212 (13.21%)  24/207 (11.59%)  10/200 (5.00%)  95/553 (17.18%) 
Psychiatric disorders         
Anxiety † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  29/553 (5.24%) 
Depression † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  71/553 (12.84%) 
Insomnia † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  49/553 (8.86%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1  10/212 (4.72%)  16/207 (7.73%)  14/200 (7.00%)  72/553 (13.02%) 
Sinus congestion † 1  11/212 (5.19%)  11/207 (5.31%)  9/200 (4.50%)  42/553 (7.59%) 
Oropharyngeal pain † 1  8/212 (3.77%)  8/207 (3.86%)  17/200 (8.50%)  51/553 (9.22%) 
Dyspnoea † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  38/553 (6.87%) 
Skin and subcutaneous tissue disorders         
Rash † 1  12/212 (5.66%)  15/207 (7.25%)  10/200 (5.00%)  83/553 (15.01%) 
Pruritus † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  28/553 (5.06%) 
Skin lesion † 2  0/212 (0.00%)  0/207 (0.00%)  0/200 (0.00%)  32/553 (5.79%) 
Vascular disorders         
Hypertension † 1  11/212 (5.19%)  9/207 (4.35%)  4/200 (2.00%)  116/553 (20.98%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1 and 13.1
2
Term from vocabulary, MedDRA 13.1
[Not Specified]
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.
Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: Abbott
Phone: 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: NCT00195702    
Other Study ID Numbers: DE019
First Submitted: September 13, 2005
First Posted: September 20, 2005
Results First Submitted: December 8, 2009
Results First Posted: March 1, 2010
Last Update Posted: August 26, 2011