CAMEO: Canadian Methotrexate and Etanercept Outcome Study

This study has been completed.
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00654368
First received: April 3, 2008
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: February 10, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Biological: Etanercept
Drug: Methotrexate

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
First patient was enrolled 28 June 2008 and last patient was enrolled 07 November 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 258 participants were enrolled, of whom 205 were randomized after 6 months and 53 were not randomized.

Reporting Groups
  Description
Non-randomized Enrolled participants received treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) but discontinued prior to completing this 6 months of treatment.
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Participant Flow:   Overall Study
    Non-randomized     Etanercept Alone     Etanercept + Methotrexate  
STARTED     53     98     107  
COMPLETED     0     50     75  
NOT COMPLETED     53     48     32  
Ineligibility determined                 6                 0                 0  
Protocol deviation                 3                 2                 1  
Non-compliance                 2                 1                 2  
Withdrawal by Subject                 5                 2                 2  
Disease progression                 21                 31                 13  
Requirement for alternative therapy                 1                 1                 1  
Physician Decision                 0                 0                 2  
Death                 1                 0                 0  
Pregnancy                 0                 0                 2  
Other                 0                 2                 3  
Adverse Event                 14                 9                 6  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Non-randomized Enrolled participants received treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) but discontinued prior to completing this 6 months of treatment.
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.
Total Total of all reporting groups

Baseline Measures
    Non-randomized     Etanercept Alone     Etanercept + Methotrexate     Total  
Number of Participants  
[units: participants]
  53     98     107     258  
Age  
[units: years]
Mean ± Standard Deviation
  56.2  ± 13.4     54.3  ± 11.9     54.4  ± 12.7     54.7  ± 12.5  
Gender  
[units: participants]
       
Female     41     72     84     197  
Male     12     26     23     61  
Race/Ethnicity, Customized  
[units: participants]
       
White or Caucasian     47     96     103     246  
Black or African American     2     1     0     3  
Hispanic or Latino     0     0     1     1  
Asian     2     0     0     2  
Native Hawaiian or other Pacific Islander     0     0     3     3  
Aborigine     1     0     0     1  
Other     1     1     0     2  
Duration of rheumatoid arthritis  
[units: participants]
       
< 2 years     11     23     23     57  
>= 2 years     42     75     84     201  
Reimbursement type  
[units: participants]
       
Private     23     48     55     126  
Public     16     33     37     86  
Combination/Other     14     17     15     46  
Disease Activity Score (DAS28-ESR) [1]
[units: participants]
       
<= 5.1     20     43     41     104  
> 5.1     33     55     66     154  
[1] The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity.



  Outcome Measures
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1.  Primary:   Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)   [ Time Frame: Month 6 (randomization) and Month 12 ]

Measure Type Primary
Measure Title Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)
Measure Description The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean change in DAS28 scores from Month 6 to Month 12 was multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity.
Time Frame Month 6 (randomization) and Month 12  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The per protocol population defined as all randomized participants with DAS28 measurements both at the 6- and 12-month visit.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  73     88  
Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)  
[units: scores on a scale]
Least Squares Mean ± Standard Error
  -0.39  ± 0.11     0.02  ± 1.26  


Statistical Analysis 1 for Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)
Groups [1] All groups
Non-Inferiority/Equivalence Test [2] Yes
Mean Difference [3] -0.41
95% Confidence Interval ( -0.75 to -0.06 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Details of power calculation, definition of non-inferiority margin, and other key parameters:
  If the lower bound of the one-sided 95% confidence interval (CI), defined below, exceeded the noninferiority margin of -0.6, then noninferiority was to be concluded.
[3] Other relevant estimation information:
  The 95% CI was calculated using the mean square error from an analysis of variance (ANOVA) fitted with effects for treatment and covariates of duration of disease, type of reimbursement, and 6 month DAS28.



2.  Secondary:   Disease Activity Score (DAS) 28 Response   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Disease Activity Score (DAS) 28 Response
Measure Description The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. Remission is defined by a DAS28 score less than 2.6. Low disease activity is defined by a DAS28 score less than or equal to 3.2. Moderate is defined as a DAS28 higher than 3.2 but lower than or equal to 5.1. DAS28 above 5.1 indicates high disease activity. End of study is Month 24 or early termination.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat population (all randomized participants); Last observation carried forward (LOCF) imputation was used. At Month 6 data were available for 95 and 105 participants in each treatment group respectively.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Disease Activity Score (DAS) 28 Response  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
   
Month 6: Remission     30.5  
  ( 21.3 to 39.8 )  
  25.7  
  ( 17.4 to 34.1 )  
Month 6: Low     16.8  
  ( 9.3 to 24.4 )  
  19.0  
  ( 11.5 to 26.6 )  
Month 6: Moderate     41.1  
  ( 31.2 to 50.9 )  
  41.9  
  ( 32.5 to 51.3 )  
Month 6: High     11.6  
  ( 5.1 to 18.0 )  
  13.3  
  ( 6.8 to 19.8 )  
Month 12: Remission     19.4  
  ( 11.6 to 27.2 )  
  23.4  
  ( 15.3 to 31.4 )  
Month 12: Low     10.2  
  ( 4.2 to 16.2 )  
  19.6  
  ( 12.1 to 27.2 )  
Month 12: Moderate     49.0  
  ( 39.1 to 58.9 )  
  44.9  
  ( 35.4 to 54.3 )  
Month 12: High     21.4  
  ( 13.3 to 29.6 )  
  12.1  
  ( 6.0 to 18.3 )  
Month 18: Remission     21.4  
  ( 13.3 to 29.6 )  
  32.7  
  ( 23.8 to 41.6 )  
Month 18: Low     12.2  
  ( 5.8 to 18.7 )  
  19.6  
  ( 12.1 to 27.2 )  
Month 18: Moderate     41.8  
  ( 32.1 to 51.6 )  
  34.6  
  ( 25.6 to 43.6 )  
Month 18: High     24.5  
  ( 16.0 to 33.0 )  
  13.1  
  ( 6.7 to 19.5 )  
End of Study: Remission     21.4  
  ( 13.3 to 29.6 )  
  29.9  
  ( 21.2 to 38.6 )  
End of Study: Low     8.2  
  ( 2.7 to 13.6 )  
  14.0  
  ( 7.4 to 20.6 )  
End of Study: Moderate     45.9  
  ( 36.1 to 55.8 )  
  39.3  
  ( 30.0 to 48.5 )  
End of Study: High     24.5  
  ( 16.0 to 33.0 )  
  16.8  
  ( 9.7 to 23.9 )  

No statistical analysis provided for Disease Activity Score (DAS) 28 Response



3.  Secondary:   Change From Baseline in Disease Activity Score 28 (DAS28)   [ Time Frame: Baseline and Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Disease Activity Score 28 (DAS28)
Measure Description The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of swollen and tender joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity measured on a 100 mm visual analog scale. The DAS28 score ranges from zero to ten. A DAS28 score above 5.1 means high disease activity whereas a DAS28 less than or equal to 3.2 indicates low disease activity. In this study, the mean changes in DAS28 scores from Baseline were multiplied by a factor of -1, such that a negative change in DAS28 indicates worsening in disease activity. End of study is Month 24 or early termination.
Time Frame Baseline and Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat; LOCF. The number of participants with available data at Month 6 was 95 and 105 in each treatment group respectively.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Change From Baseline in Disease Activity Score 28 (DAS28)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from Baseline to Month 6     1.97  ± 1.23     1.97  ± 1.51  
Change from Baseline to Month 12     1.43  ± 1.27     1.91  ± 1.61  
Change from Baseline to Month 18     1.35  ± 1.30     2.01  ± 1.59  
Change from Baseline to End of Study     1.37  ± 1.32     1.86  ± 1.71  

No statistical analysis provided for Change From Baseline in Disease Activity Score 28 (DAS28)



4.  Secondary:   Drug Persistence   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Drug Persistence
Measure Description Drug persistence is defined as the percentage of participants receiving etanercept at 6, 12, 18, and 24 months.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to Treat Analysis Set

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Drug Persistence  
[units: percentage of participants]
   
Month 6     100     100  
Month 12     93.2     87.6  
Month 18     81.9     78.8  
Month 24     51.4     69.5  

No statistical analysis provided for Drug Persistence



5.  Secondary:   Change From Baseline in Modified Total Sharp Score (mTSS)   [ Time Frame: Baseline, Month 12 and Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Modified Total Sharp Score (mTSS)
Measure Description The modified Total Sharp Score (mTSS) is a measure of change in joint health. X-rays of hands and feet were scored in a blinded manner by an independent reader. Joints were scored for erosions on a scale from 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale from 0 (no damage) to 4 (bony ankylosis or complete luxation). Erosion scores and narrowing scores were added to obtain the total mTSS score, ranging from 0 (normal) to 448 (maximal disease). An increase in mTSS from Baseline (represented by a positive change from Baseline score) indicates disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease (negative change from Baseline score) represents improvement. End of study is Month 24 or early termination.
Time Frame Baseline, Month 12 and Month 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  94     104  
Change From Baseline in Modified Total Sharp Score (mTSS)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from Baseline to Month 12 (n=89, 102)     0.3  ± 1.9     0.1  ± 1.2  
Change from Baseline to End of Study (n=94, 104)     0.4  ± 1.9     0.0  ± 1.4  

No statistical analysis provided for Change From Baseline in Modified Total Sharp Score (mTSS)



6.  Secondary:   Change From Baseline in Joint Erosion Score   [ Time Frame: Baseline, Month 12 and Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Joint Erosion Score
Measure Description X-rays of hands and feet were read centrally and in a blinded manner. Sixteen joints on each hand/wrist and 6 joints on each foot were scored for erosions on a scale of 0 to 5 (or for the feet from 0 to 10, with each side of the joint independently scored from 0 to 5) according to the following: One point is scored if erosions are discrete, rising to 2, 3, 4, or 5 depending on the amount of surface area affected (complete collapse of the bone is scored as 5). Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion) to 280 (worst). A large increase in erosion score is indicative of worsening, whereas a small change or no change is indicative of inhibition of joint erosion. End of study is Month 24 or early termination.
Time Frame Baseline, Month 12 and Month 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Radiographic Analysis Set - All randomized participants with a Baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  94     104  
Change From Baseline in Joint Erosion Score  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from Baseline to Month 12 (n=89, 102)     0.0  ± 0.6     0.0  ± 0.6  
Change from Baseline to End of Study (n=94, 104)     0.1  ± 0.6     0.0  ± 0.7  

No statistical analysis provided for Change From Baseline in Joint Erosion Score



7.  Secondary:   Change From Baseline in Joint Space Narrowing   [ Time Frame: Baseline, Month 12 and Month 24 ]

Measure Type Secondary
Measure Title Change From Baseline in Joint Space Narrowing
Measure Description

X-rays of hands and feet were read centrally and in a blinded manner. Joint space narrowing (JSN) scores were recorded for each hand/wrist (15 joints) and each foot (6 joints) on a 5-point scale scored as follows:

0 = normal; 1 = focal or doubtful; 2 = generalised, less than 50% of the original joint space; 3 = generalised, more than 50% of the original joint space or subluxation; 4 = bony ankylosis or complete luxation. The scores were summed to calculate the total JSN score ranging from 0 to 168 (worst). A large increase in joint narrowing score is indicative of worsening, whereas a small change or no change is indicative of inhibition of JSN.

End of study is Month 24 or early termination.

Time Frame Baseline, Month 12 and Month 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  94     104  
Change From Baseline in Joint Space Narrowing  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from Baseline to Month 12 (n=89, 102)     0.2  ± 1.5     0.1  ± 0.9  
Change from Baseline to End of Study (n=94, 104)     0.3  ± 1.5     -0.0  ± 1.0  

No statistical analysis provided for Change From Baseline in Joint Space Narrowing



8.  Secondary:   Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)
Measure Description The HAQ disability index is a patient-reported questionnaire specific for rheumatoid arthritis that addresses health-related quality of life. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants choose from four response categories, ranging from 'without any difficulty' (score=0) to 'unable to do' (score=3). The overall score is the average of each of the 8 category scores and ranges from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A negative change score indicates an improvement. End of study is Month 24 or early termination.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat analysis set; LOCF

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from Month 6 to Month 12     0.148  ± 0.354     0.026  ± 0.430  
Change from Month 6 to Month 18     0.179  ± 0.452     -0.004  ± 0.485  
Change from Month 6 to End of Study     0.198  ± 0.448     0.016  ± 0.539  

No statistical analysis provided for Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)



9.  Secondary:   Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)
Measure Description The HAQ pain visual analog scale (VAS) is a measure of pain on a continuous 100 point scale. Participants were asked to indicate how much pain they had in the past week as a result of their illness on a horizontal line from 0 (no pain) to 100 (severe pain). End of study is Month 24 or early termination.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat analysis set with available data; LOCF

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     106  
Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Change from month 6 to month 12     7.3  ± 21.3     2.4  ± 23.8  
Change from month 6 to month 18     8.0  ± 25.6     1.8  ± 24.4  
Change from month 6 to end of study     8.7  ± 26.1     5.1  ± 27.3  

No statistical analysis provided for Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)



10.  Secondary:   Change From Month 6 in Short Form 36 Health Survey (SF-36)   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Month 6 in Short Form 36 Health Survey (SF-36)
Measure Description

The SF-36 assesses the general quality of life (QOL) of participants by evaluating the domains of physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. The questionnaire consists of 36 questions that are completed by the participant.

The SF-36 is split into two major components: physical health and mental health. Under physical health are the following four domains: physical health, bodily pain, physical functioning and physical role limitations. Under the mental health domain there are four domains; mental health, vitality, social functioning, and emotional role limitation. The individual domain scores are aggregated to derive a physical-component summary score and a mental-component summary score which range from 0 to 100, with higher scores indicating a better level of functioning.

End of study is month 24 or early termination.

Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat analysis set with available SF-36 data at month 6; LOCF

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     106  
Change From Month 6 in Short Form 36 Health Survey (SF-36)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Physical Component: Change at Month 12     -1.74  ± 8.87     -0.30  ± 7.40  
Physical Component: Change at Month 18     -3.28  ± 9.40     -0.10  ± 8.61  
Physical Component: Change at End of Study     -3.08  ± 8.95     -0.75  ± 9.42  
Mental Health Component: Change at 12 Months     -1.16  ± 10.29     -1.27  ± 9.40  
Mental Health Component: Change at 18 Months     -0.30  ± 9.40     -0.92  ± 10.34  
Mental Health Component: Change at End of Study     -1.30  ± 10.47     0.08  ± 10.70  

No statistical analysis provided for Change From Month 6 in Short Form 36 Health Survey (SF-36)



11.  Secondary:   Change From Month 6 in Work Productivity and Activity Impairment (WPAI)   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Month 6 in Work Productivity and Activity Impairment (WPAI)
Measure Description This 6-item assessment measures productivity losses during the past 7 days and includes measures on work time missed due to health, impairment while working due to health (the participant’s assessment of the degree to which health affected their productivity while working), overall work impairment due to health (takes into account both hours missed due to health and the participant’s assessment of the degree to which health affected their productivity while working) and activity impairment due to health (the degree in which health problems affected their ability to do regular daily activities). Scores for each measure are expressed from 0 to 100 with higher numbers indicating greater impairment and less productivity, i.e., worse outcomes. For each measure change from Month 6 is reported; a negative change score indicates improvement. End of study is month 24 or early termination.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat analysis set with available data; Work time missed and work impairment scores are only calculated for participants who were employed at the time. LOCF imputation was used.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Change From Month 6 in Work Productivity and Activity Impairment (WPAI)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Work Time Missed: Month 12 (n=45, 44)     -4.2  ± 19.3     -0.3  ± 15.0  
Work Time Missed: Month 18 (n=42, 43)     -5.5  ± 20.2     0.9  ± 17.5  
Work Time Missed: End of Study (n=42, 44)     -3.8  ± 23.3     -0.1  ± 15.6  
Work Impairment: Month 12 (n=43, 46)     5.8  ± 15.0     -1.3  ± 19.6  
Work Impairment: Month 18 (n=40, 45)     7.3  ± 24.2     -1.3  ± 21.8  
Work Impairment: End of Study (n=40, 46)     10.5  ± 22.2     -1.7  ± 24.1  
Overall Work Impairment: Month 12 (n=43, 44)     3.4  ± 16.8     -0.7  ± 20.1  
Overall Work Impairment: Month 18 (n=40, 43)     4.3  ± 26.0     -2.7  ± 24.2  
Overall Work Impairment: End of Study (n=40, 44)     8.2  ± 26.4     -1.7  ± 25.0  
Activity Impairment: Month 12 (n=98, 107)     6.7  ± 21.2     4.3  ± 22.7  
Activity Impairment: Month 18 (n=98, 107)     7.4  ± 25.8     0.7  ± 25.3  
Activity Impairment: End of Study (n=98, 107)     9.1  ± 27.0     1.8  ± 27.4  

No statistical analysis provided for Change From Month 6 in Work Productivity and Activity Impairment (WPAI)



12.  Secondary:   Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)   [ Time Frame: Month 6, 12, 18 and 24 ]

Measure Type Secondary
Measure Title Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)
Measure Description The Treatment Satisfaction Questionnaire for Medication is a 14-item self-administered questionnaire which measures patients’ experiences with their medication on four dimensions: effectiveness, side effects, convenience and global satisfaction. Optional responses are: Extremely Dissatisfied (1), Very Dissatisfied (2), Dissatisfied (3), Somewhat Satisfied (4), Satisfied (5), Very Satisfied (6), and Extremely Satisfied (7). For each dimension, responses are added and transformed to a scale from 0 – 100, where higher scores indicate greater satisfaction. Change from Month 6 is reported for each dimension; a positive change score indicates improvement. End of study is Month 24 or early termination.
Time Frame Month 6, 12, 18 and 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat analysis set with available data; LOCF. n indicates the number of participants with available data at each time point.

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)  
[units: scores on a scale]
Mean ± Standard Deviation
   
Effectiveness: Month 12 (n=98, 107)     -5.0  ± 27.3     -1.2  ± 30.0  
Effectiveness: Month 18 (n=98, 107)     -7.4  ± 25.2     -1.1  ± 29.4  
Effectiveness: End of Study (n=98, 107)     -5.0  ± 25.6     -1.5  ± 29.7  
Side Effects: Month 12 (n= 97, 106)     2.5  ± 21.4     0.6  ± 19.0  
Side Effects: Month 18 (n=97, 106)     -0.5  ± 24.8     0.9  ± 17.9  
Side Effects: End of Study (n=97, 106)     0.6  ± 24.7     1.2  ± 19.4  
Convenience: Month 12 (n=97, 107)     0.6  ± 16.5     0.9  ± 14.3  
Convenience: Month 18 (n=97, 107)     0.9  ± 15.6     -0.8  ± 15.1  
Convenience: End of Study (n=97, 107)     2.0  ± 15.0     -0.6  ± 15.3  
Global Satisfaction: Month 12 (n=97, 107)     -1.3  ± 19.4     1.2  ± 17.3  
Global Satisfaction: Month 18 (n=97, 107)     -6.3  ± 24.0     -1.5  ± 20.0  
Global Satisfaction: End of Study (n=97, 107)     -5.4  ± 23.7     -1.3  ± 20.9  

No statistical analysis provided for Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)



13.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: 25 months ]

Measure Type Secondary
Measure Title Number of Participants With Adverse Events (AEs)
Measure Description A serious adverse event (SAE) is defined by regulatory authorities as one that: • is fatal • is life threatening • requires in-patient hospitalization or prolongation of existing hospitalization • results in persistent or significant disability/incapacity • is a congenital anomaly/birth defect • other significant medical hazard.
Time Frame 25 months  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Analysis Set

Reporting Groups
  Description
Etanercept Alone After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to discontinue methotrexate (tapered over 6 weeks) and continue etanercept alone for an additional 18 months.
Etanercept + Methotrexate After six months of treatment with 50 mg/week subcutaneous etanercept added to existing methotrexate therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses) participants were randomized to continue both etanercept plus methotrexate for an additional 18 months.

Measured Values
    Etanercept Alone     Etanercept + Methotrexate  
Number of Participants Analyzed  
[units: participants]
  98     107  
Number of Participants With Adverse Events (AEs)  
[units: participants]
   
Any adverse event     86     92  
Serious adverse event     11     17  
AEs leading to withdrawal from study drug     9     6  

No statistical analysis provided for Number of Participants With Adverse Events (AEs)




  Serious Adverse Events


  Other Adverse Events


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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


No publications provided


Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00654368     History of Changes
Other Study ID Numbers: 20070301
Study First Received: April 3, 2008
Results First Received: February 10, 2014
Last Updated: July 14, 2014
Health Authority: Canada: Institutional Review Board