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CAMEO: Canadian Methotrexate and Etanercept Outcome Study

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ClinicalTrials.gov Identifier: NCT00654368
Recruitment Status : Completed
First Posted : April 8, 2008
Results First Posted : June 13, 2014
Last Update Posted : July 23, 2014
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by (Responsible Party):
Amgen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Rheumatoid Arthritis
Interventions Biological: Etanercept
Drug: Methotrexate
Enrollment 258
Recruitment Details First patient was enrolled 28 June 2008 and last patient was enrolled 07 November 2010.
Pre-assignment Details A total of 258 participants were enrolled, of whom 205 were randomized after 6 months and 53 were not randomized.
Arm/Group Title Non-randomized Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description 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. 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. 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.
Period Title: Overall Study
Started 53 98 107
Completed 0 50 75
Not Completed 53 48 32
Reason Not Completed
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
Arm/Group Title Non-randomized Etanercept Alone Etanercept + Methotrexate Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 53 98 107 258
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 53 participants 98 participants 107 participants 258 participants
56.2  (13.4) 54.3  (11.9) 54.4  (12.7) 54.7  (12.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 53 participants 98 participants 107 participants 258 participants
Female
41
  77.4%
72
  73.5%
84
  78.5%
197
  76.4%
Male
12
  22.6%
26
  26.5%
23
  21.5%
61
  23.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 98 participants 107 participants 258 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  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 98 participants 107 participants 258 participants
< 2 years 11 23 23 57
>= 2 years 42 75 84 201
Reimbursement type  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 98 participants 107 participants 258 participants
Private 23 48 55 126
Public 16 33 37 86
Combination/Other 14 17 15 46
Disease Activity Score (DAS28-ESR)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 53 participants 98 participants 107 participants 258 participants
<= 5.1 20 43 41 104
> 5.1 33 55 66 154
[1]
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.
1.Primary Outcome
Title Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The per protocol population defined as all randomized participants with DAS28 measurements both at the 6- and 12-month visit.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 73 88
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-0.39  (0.11) 0.02  (1.26)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Etanercept Alone, Etanercept + Methotrexate
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments 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.
Method of Estimation Estimation Parameter Mean Difference
Estimated Value -0.41
Confidence Interval (2-Sided) 95%
-0.75 to -0.06
Estimation Comments 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 Outcome
Title Disease Activity Score (DAS) 28 Response
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
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)
3.Secondary Outcome
Title Change From Baseline in Disease Activity Score 28 (DAS28)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat; LOCF. The number of participants with available data at Month 6 was 95 and 105 in each treatment group respectively.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
4.Secondary Outcome
Title Drug Persistence
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Analysis Set
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Measure Type: Number
Unit of Measure: 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
5.Secondary Outcome
Title Change From Baseline in Modified Total Sharp Score (mTSS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 94 104
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
6.Secondary Outcome
Title Change From Baseline in Joint Erosion Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Radiographic Analysis Set - All randomized participants with a Baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 94 104
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
7.Secondary Outcome
Title Change From Baseline in Joint Space Narrowing
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Radiographic Analysis Set - All randomized participants with a baseline and at least 1 post baseline radiographic assessment. LOCF imputation was used.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 94 104
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
8.Secondary Outcome
Title Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis set; LOCF
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
9.Secondary Outcome
Title Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis set with available data; LOCF
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 106
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
10.Secondary Outcome
Title Change From Month 6 in Short Form 36 Health Survey (SF-36)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to treat analysis set with available SF-36 data at month 6; LOCF
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 106
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
11.Secondary Outcome
Title Change From Month 6 in Work Productivity and Activity Impairment (WPAI)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
12.Secondary Outcome
Title Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM)
Hide 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
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Hide Analysis Population Description
Intent to treat analysis set with available data; LOCF. n indicates the number of participants with available data at each time point.
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
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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.
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.
Overall Number of Participants Analyzed 98 107
Mean (Standard Deviation)
Unit of Measure: scores on a scale
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)
13.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide 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
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Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 98 107
Measure Type: Number
Unit of Measure: participants
Any adverse event 86 92
Serious adverse event 11 17
AEs leading to withdrawal from study drug 9 6
Time Frame 25 months
Adverse Event Reporting Description The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
 
Arm/Group Title Non-randomized Etanercept Alone Etanercept + Methotrexate
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
Non-randomized Etanercept Alone Etanercept + Methotrexate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Non-randomized Etanercept Alone Etanercept + Methotrexate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/53 (13.21%)   11/98 (11.22%)   17/107 (15.89%) 
Cardiac disorders       
Atrial fibrillation  1  1/53 (1.89%)  1/98 (1.02%)  0/107 (0.00%) 
Cardiac failure chronic  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Coronary artery disease  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Prinzmetal angina  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Eye disorders       
Ulcerative keratitis  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Gastrointestinal disorders       
Colitis  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Small intestinal obstruction  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Infections and infestations       
Bronchopneumonia  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Cellulitis  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Device related infection  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Diverticulitis  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Infectious pleural effusion  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Lung abscess  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Pneumonia  1  2/53 (3.77%)  3/98 (3.06%)  2/107 (1.87%) 
Sepsis  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Urinary tract infection  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Injury, poisoning and procedural complications       
Tibia fracture  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Osteoarthritis  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Rheumatoid arthritis  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Lung cancer metastatic  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Lung squamous cell carcinoma stage unspecified  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Non-Hodgkin's lymphoma  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Prostate cancer  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Squamous cell carcinoma  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Transitional cell carcinoma  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Nervous system disorders       
Cerebrovascular accident  1  1/53 (1.89%)  1/98 (1.02%)  0/107 (0.00%) 
Demyelinating polyneuropathy  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
VIIth nerve paralysis  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
Abortion spontaneous  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Psychiatric disorders       
Depression  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Suicide attempt  1  0/53 (0.00%)  0/98 (0.00%)  2/107 (1.87%) 
Renal and urinary disorders       
Renal cyst ruptured  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Renal failure  1  0/53 (0.00%)  1/98 (1.02%)  0/107 (0.00%) 
Reproductive system and breast disorders       
Uterine prolapse  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Respiratory, thoracic and mediastinal disorders       
Alveolitis  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Chronic obstructive pulmonary disease  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Interstitial lung disease  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Pneumonitis  1  1/53 (1.89%)  1/98 (1.02%)  0/107 (0.00%) 
Pulmonary embolism  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Surgical and medical procedures       
Hip arthroplasty  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Vascular disorders       
Aortic stenosis  1  0/53 (0.00%)  0/98 (0.00%)  1/107 (0.93%) 
Deep vein thrombosis  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Superior vena cava syndrome  1  1/53 (1.89%)  0/98 (0.00%)  0/107 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Non-randomized Etanercept Alone Etanercept + Methotrexate
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   18/53 (33.96%)   56/98 (57.14%)   73/107 (68.22%) 
Gastrointestinal disorders       
Nausea  1  3/53 (5.66%)  2/98 (2.04%)  6/107 (5.61%) 
General disorders       
Fatigue  1  1/53 (1.89%)  3/98 (3.06%)  6/107 (5.61%) 
Injection site reaction  1  2/53 (3.77%)  6/98 (6.12%)  7/107 (6.54%) 
Infections and infestations       
Bronchitis  1  0/53 (0.00%)  5/98 (5.10%)  7/107 (6.54%) 
Influenza  1  0/53 (0.00%)  7/98 (7.14%)  5/107 (4.67%) 
Nasopharyngitis  1  1/53 (1.89%)  10/98 (10.20%)  12/107 (11.21%) 
Pneumonia  1  1/53 (1.89%)  1/98 (1.02%)  9/107 (8.41%) 
Sinusitis  1  1/53 (1.89%)  8/98 (8.16%)  11/107 (10.28%) 
Upper respiratory tract infection  1  2/53 (3.77%)  13/98 (13.27%)  19/107 (17.76%) 
Urinary tract infection  1  4/53 (7.55%)  3/98 (3.06%)  8/107 (7.48%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  0/53 (0.00%)  4/98 (4.08%)  7/107 (6.54%) 
Rheumatoid arthritis  1  1/53 (1.89%)  5/98 (5.10%)  10/107 (9.35%) 
Nervous system disorders       
Headache  1  5/53 (9.43%)  9/98 (9.18%)  9/107 (8.41%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  0/53 (0.00%)  6/98 (6.12%)  5/107 (4.67%) 
Oropharyngeal pain  1  0/53 (0.00%)  5/98 (5.10%)  4/107 (3.74%) 
Skin and subcutaneous tissue disorders       
Rash  1  1/53 (1.89%)  4/98 (4.08%)  9/107 (8.41%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 15.1
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 Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results aftercompletion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Amgen Inc.
Phone: 866-572-6436
Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00654368    
Other Study ID Numbers: 20070301
First Submitted: April 3, 2008
First Posted: April 8, 2008
Results First Submitted: February 10, 2014
Results First Posted: June 13, 2014
Last Update Posted: July 23, 2014