CAMEO: Canadian Methotrexate and Etanercept Outcome Study
Study Details
Study Description
Brief Summary
The purpose of the study is to evaluate the use of etanercept in the treatment of rheumatoid arthritis with or without methotrexate treatment over a 24 month period
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
This noninferiority study was a multicenter, open-label, randomized trial of patients with rheumatoid arthritis (RA). Patients who did not have an adequate response to methotrexate (MTX) had etanercept (50 mg/week subcutaneously [SC]) added to existing MTX therapy of at least 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses of MTX) at baseline and were followed for 6 months. After 6 months of therapy, participants were randomized in a 1:1 ratio to one of the 2 treatment arms: either discontinue MTX (tapered over 6 weeks) and continue etanercept alone or continue both etanercept plus MTX for an additional 18 months.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: 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. |
Biological: Etanercept
Commercially available etanercept administered subcutaneously at 50 mg/week.
Other Names:
Drug: Methotrexate
Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)
|
| Experimental: Etanercept Only 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. |
Biological: Etanercept
Commercially available etanercept administered subcutaneously at 50 mg/week.
Other Names:
Drug: Methotrexate
Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)
|
Outcome Measures
Primary Outcome Measures
- Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28) [Month 6 (randomization) and Month 12]
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.
Secondary Outcome Measures
- Disease Activity Score (DAS) 28 Response [Month 6, 12, 18 and 24]
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.
- Change From Baseline in Disease Activity Score 28 (DAS28) [Baseline and Month 6, 12, 18 and 24]
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.
- Drug Persistence [Month 6, 12, 18 and 24]
Drug persistence is defined as the percentage of participants receiving etanercept at 6, 12, 18, and 24 months.
- Change From Baseline in Modified Total Sharp Score (mTSS) [Baseline, Month 12 and Month 24]
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.
- Change From Baseline in Joint Erosion Score [Baseline, Month 12 and Month 24]
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.
- Change From Baseline in Joint Space Narrowing [Baseline, Month 12 and Month 24]
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.
- Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI) [Month 6, 12, 18 and 24]
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.
- Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS) [Month 6, 12, 18 and 24]
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.
- Change From Month 6 in Short Form 36 Health Survey (SF-36) [Month 6, 12, 18 and 24]
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.
- Change From Month 6 in Work Productivity and Activity Impairment (WPAI) [Month 6, 12, 18 and 24]
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.
- Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM) [Month 6, 12, 18 and 24]
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.
- Number of Participants With Adverse Events (AEs) [25 months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 years of age or older at the baseline visit
-
An American College of Rheumatology(ACR) diagnosis of rheumatoid arthritis with onset of symptoms of at least 6 months
-
Active disease of at least 3 swollen joints from the Disease Activity Severity 28 at the baseline visit
-
A Disease Activity Severity 28 score of ≥ 3.2 at the baseline visit
-
Have not previously received etanercept therapy
-
Able to start etanercept therapy per the approved product monograph
-
Able to continue methotrexate therapy per the approved product monograph and have received a dose of at least 15 mg/wk (or 10 mg/wk in the case of documented intolerance to higher doses) for at least 12 weeks and this dose has been stable at least 4 weeks before the baseline visit
-
The patient or legally acceptable representative must provide written informed consent for participation in the study before any study specific procedures are performed
Exclusion Criteria:
-
Patients who have a positive purified protein derivative (PPD) skin test and who do not have a documented course of anti-tuberculosis therapy. Patients with a positive PPD skin test (equal to or greater than 5 mm), a negative chest x-ray at screening which should be repeated if indicated during of the study, at low risk based on exposure and travel and have initiated a course of anti-tuberculosis therapy of which at least 8 weeks have been completed would be eligible for the study. The full course of anti-tuberculosis therapy must be completed
-
Patients who have previously received infliximab or adalimumab
-
Active infections within 2 weeks of the baseline visit or during the study period
-
Any history of human immunodeficiency (HIV) infection, untreated tuberculosis, multiple sclerosis, congestive heart failure, hepatitis B, hepatitis C, cytopenia, prior or current use of cyclophosphamide or malignancy (other than basal cell carcinoma or squamous cell carcinoma of the skin, or in situ carcinoma of the cervix) in the past 5 years
-
Women who are pregnant or lactating or of childbearing potential who are not using adequate contraception
-
Receipt of any investigational therapy within 4 weeks of the initiation of study medication or during the study period
-
Presence of any significant and uncontrolled medical condition, which in the investigator's opinion precludes the use of etanercept, as outlined in the product monograph
-
Participants not available for follow-up assessment or unable to comply with study procedures
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Vancouver | British Columbia | Canada | V5Z 3Y1 |
| 2 | Research Site | Victoria | British Columbia | Canada | V8P 5P6 |
| 3 | Research Site | Victoria | British Columbia | Canada | V8V 3P9 |
| 4 | Research Site | Winnipeg | Manitoba | Canada | R3A 1M3 |
| 5 | Research Site | Quispamsis | New Brunswick | Canada | E2E 4J8 |
| 6 | Research Site | St. John's | Newfoundland and Labrador | Canada | A1A 5E8 |
| 7 | Research Site | St. John's | Newfoundland and Labrador | Canada | A1C 5B8 |
| 8 | Research Site | Sydney | Nova Scotia | Canada | B1S 3N1 |
| 9 | Research Site | Bowmanville | Ontario | Canada | L1C 1P6 |
| 10 | Research Site | Brampton | Ontario | Canada | L6T 3J1 |
| 11 | Research Site | Burlington | Ontario | Canada | L7R 4B7 |
| 12 | Research Site | Hamilton | Ontario | Canada | L8N 1Y2 |
| 13 | Research Site | London | Ontario | Canada | N6A 4V2 |
| 14 | Research Site | Mississauga | Ontario | Canada | L5M 2V8 |
| 15 | Research Site | Newmarket | Ontario | Canada | L3Y 3R7 |
| 16 | Research Site | Ottawa | Ontario | Canada | K1S 1C2 |
| 17 | Research Site | St Catharines | Ontario | Canada | L2N 7E4 |
| 18 | Research Site | Toronto | Ontario | Canada | M5G 1X5 |
| 19 | Research Site | Toronto | Ontario | Canada | M9B 6H8 |
| 20 | Research Site | Laval | Quebec | Canada | H7T 2P5 |
| 21 | Research Site | Montreal | Quebec | Canada | H2L 1S6 |
| 22 | Research Site | Montreal | Quebec | Canada | H3T 1E2 |
| 23 | Research Site | Montreal | Quebec | Canada | H3Z 2Z3 |
| 24 | Research Site | Rimouski | Quebec | Canada | G5L 8W1 |
| 25 | Research Site | Saint Leonard | Quebec | Canada | H1R 1X8 |
| 26 | Research Site | Saint-Eustache | Quebec | Canada | J7P 4J2 |
| 27 | Research Site | Saskatoon | Saskatchewan | Canada | S7K 0H6 |
| 28 | Research Site | Quebec | Canada | G1V 3M7 |
Sponsors and Collaborators
- Amgen
- Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- 20070301
Study Results
Participant Flow
| Recruitment Details | First patient was enrolled 28 June 2008 and last patient was enrolled 07 November 2010. |
|---|---|
| Pre-assignment Detail | 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 |
|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Non-randomized | Etanercept Alone | Etanercept + Methotrexate | Total |
|---|---|---|---|---|
| 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 Participants | 53 | 98 | 107 | 258 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
56.2
(13.4)
|
54.3
(11.9)
|
54.4
(12.7)
|
54.7
(12.5)
|
| Sex: Female, Male (Count of 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 (participants) [Number] | ||||
| White or Caucasian |
47
88.7%
|
96
98%
|
103
96.3%
|
246
95.3%
|
| Black or African American |
2
3.8%
|
1
1%
|
0
0%
|
3
1.2%
|
| Hispanic or Latino |
0
0%
|
0
0%
|
1
0.9%
|
1
0.4%
|
| Asian |
2
3.8%
|
0
0%
|
0
0%
|
2
0.8%
|
| Native Hawaiian or other Pacific Islander |
0
0%
|
0
0%
|
3
2.8%
|
3
1.2%
|
| Aborigine |
1
1.9%
|
0
0%
|
0
0%
|
1
0.4%
|
| Other |
1
1.9%
|
1
1%
|
0
0%
|
2
0.8%
|
| Duration of rheumatoid arthritis (participants) [Number] | ||||
| < 2 years |
11
20.8%
|
23
23.5%
|
23
21.5%
|
57
22.1%
|
| >= 2 years |
42
79.2%
|
75
76.5%
|
84
78.5%
|
201
77.9%
|
| Reimbursement type (participants) [Number] | ||||
| Private |
23
43.4%
|
48
49%
|
55
51.4%
|
126
48.8%
|
| Public |
16
30.2%
|
33
33.7%
|
37
34.6%
|
86
33.3%
|
| Combination/Other |
14
26.4%
|
17
17.3%
|
15
14%
|
46
17.8%
|
| Disease Activity Score (DAS28-ESR) (participants) [Number] | ||||
| <= 5.1 |
20
37.7%
|
43
43.9%
|
41
38.3%
|
104
40.3%
|
| > 5.1 |
33
62.3%
|
55
56.1%
|
66
61.7%
|
154
59.7%
|
Outcome Measures
| Title | Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 73 | 88 |
| Least Squares Mean (Standard Error) [scores on a scale] |
-0.39
(0.11)
|
0.02
(1.26)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Etanercept Alone, Etanercept + Methotrexate |
|---|---|---|
| Comments | ||
| 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. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference |
| Estimated Value | -0.41 | |
| Confidence Interval |
(2-Sided) 95% -0.75 to -0.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| 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. | |
| Title | Disease Activity Score (DAS) 28 Response |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| Month 6: Remission |
30.5
57.5%
|
25.7
26.2%
|
| Month 6: Low |
16.8
31.7%
|
19.0
19.4%
|
| Month 6: Moderate |
41.1
77.5%
|
41.9
42.8%
|
| Month 6: High |
11.6
21.9%
|
13.3
13.6%
|
| Month 12: Remission |
19.4
36.6%
|
23.4
23.9%
|
| Month 12: Low |
10.2
19.2%
|
19.6
20%
|
| Month 12: Moderate |
49.0
92.5%
|
44.9
45.8%
|
| Month 12: High |
21.4
40.4%
|
12.1
12.3%
|
| Month 18: Remission |
21.4
40.4%
|
32.7
33.4%
|
| Month 18: Low |
12.2
23%
|
19.6
20%
|
| Month 18: Moderate |
41.8
78.9%
|
34.6
35.3%
|
| Month 18: High |
24.5
46.2%
|
13.1
13.4%
|
| End of Study: Remission |
21.4
40.4%
|
29.9
30.5%
|
| End of Study: Low |
8.2
15.5%
|
14.0
14.3%
|
| End of Study: Moderate |
45.9
86.6%
|
39.3
40.1%
|
| End of Study: High |
24.5
46.2%
|
16.8
17.1%
|
| Title | Change From Baseline in Disease Activity Score 28 (DAS28) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| 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)
|
| Title | Drug Persistence |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to Treat Analysis Set |
| Arm/Group Title | Etanercept Alone | Etanercept + Methotrexate |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| Month 6 |
100
188.7%
|
100
102%
|
| Month 12 |
93.2
175.8%
|
87.6
89.4%
|
| Month 18 |
81.9
154.5%
|
78.8
80.4%
|
| Month 24 |
51.4
97%
|
69.5
70.9%
|
| Title | Change From Baseline in Modified Total Sharp Score (mTSS) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 94 | 104 |
| 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)
|
| Title | Change From Baseline in Joint Erosion Score |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 94 | 104 |
| 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)
|
| Title | Change From Baseline in Joint Space Narrowing |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 94 | 104 |
| 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)
|
| Title | Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis set; LOCF |
| Arm/Group Title | Etanercept Alone | Etanercept + Methotrexate |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| 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)
|
| Title | Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis set with available data; LOCF |
| Arm/Group Title | Etanercept Alone | Etanercept + Methotrexate |
|---|---|---|
| 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. |
| Measure Participants | 98 | 106 |
| 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)
|
| Title | Change From Month 6 in Short Form 36 Health Survey (SF-36) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent to treat analysis set with available SF-36 data at month 6; LOCF |
| Arm/Group Title | Etanercept Alone | Etanercept + Methotrexate |
|---|---|---|
| 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. |
| Measure Participants | 98 | 106 |
| 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)
|
| Title | Change From Month 6 in Work Productivity and Activity Impairment (WPAI) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| 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)
|
| Title | Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| 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)
|
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Analysis Set |
| Arm/Group Title | Etanercept Alone | Etanercept + Methotrexate |
|---|---|---|
| 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. |
| Measure Participants | 98 | 107 |
| Any adverse event |
86
162.3%
|
92
93.9%
|
| Serious adverse event |
11
20.8%
|
17
17.3%
|
| AEs leading to withdrawal from study drug |
9
17%
|
6
6.1%
|
Adverse Events
| 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 | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Non-randomized | Etanercept Alone | Etanercept + Methotrexate | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/53 (13.2%) | 11/98 (11.2%) | 17/107 (15.9%) | |||
| Cardiac disorders | ||||||
| Atrial fibrillation | 1/53 (1.9%) | 1/98 (1%) | 0/107 (0%) | |||
| Cardiac failure chronic | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Coronary artery disease | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Prinzmetal angina | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Eye disorders | ||||||
| Ulcerative keratitis | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Gastrointestinal disorders | ||||||
| Colitis | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Small intestinal obstruction | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Infections and infestations | ||||||
| Bronchopneumonia | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Cellulitis | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Device related infection | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Diverticulitis | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Infectious pleural effusion | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Lung abscess | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Pneumonia | 2/53 (3.8%) | 3/98 (3.1%) | 2/107 (1.9%) | |||
| Sepsis | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Urinary tract infection | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Injury, poisoning and procedural complications | ||||||
| Tibia fracture | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Osteoarthritis | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Rheumatoid arthritis | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Lung cancer metastatic | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Lung squamous cell carcinoma stage unspecified | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Non-Hodgkin's lymphoma | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Prostate cancer | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Squamous cell carcinoma | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Transitional cell carcinoma | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Nervous system disorders | ||||||
| Cerebrovascular accident | 1/53 (1.9%) | 1/98 (1%) | 0/107 (0%) | |||
| Demyelinating polyneuropathy | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| VIIth nerve paralysis | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion spontaneous | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Psychiatric disorders | ||||||
| Depression | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Suicide attempt | 0/53 (0%) | 0/98 (0%) | 2/107 (1.9%) | |||
| Renal and urinary disorders | ||||||
| Renal cyst ruptured | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Renal failure | 0/53 (0%) | 1/98 (1%) | 0/107 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Uterine prolapse | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Alveolitis | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Chronic obstructive pulmonary disease | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Interstitial lung disease | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Pneumonitis | 1/53 (1.9%) | 1/98 (1%) | 0/107 (0%) | |||
| Pulmonary embolism | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Surgical and medical procedures | ||||||
| Hip arthroplasty | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Vascular disorders | ||||||
| Aortic stenosis | 0/53 (0%) | 0/98 (0%) | 1/107 (0.9%) | |||
| Deep vein thrombosis | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
| Superior vena cava syndrome | 1/53 (1.9%) | 0/98 (0%) | 0/107 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Non-randomized | Etanercept Alone | Etanercept + Methotrexate | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 18/53 (34%) | 56/98 (57.1%) | 73/107 (68.2%) | |||
| Gastrointestinal disorders | ||||||
| Nausea | 3/53 (5.7%) | 2/98 (2%) | 6/107 (5.6%) | |||
| General disorders | ||||||
| Fatigue | 1/53 (1.9%) | 3/98 (3.1%) | 6/107 (5.6%) | |||
| Injection site reaction | 2/53 (3.8%) | 6/98 (6.1%) | 7/107 (6.5%) | |||
| Infections and infestations | ||||||
| Bronchitis | 0/53 (0%) | 5/98 (5.1%) | 7/107 (6.5%) | |||
| Influenza | 0/53 (0%) | 7/98 (7.1%) | 5/107 (4.7%) | |||
| Nasopharyngitis | 1/53 (1.9%) | 10/98 (10.2%) | 12/107 (11.2%) | |||
| Pneumonia | 1/53 (1.9%) | 1/98 (1%) | 9/107 (8.4%) | |||
| Sinusitis | 1/53 (1.9%) | 8/98 (8.2%) | 11/107 (10.3%) | |||
| Upper respiratory tract infection | 2/53 (3.8%) | 13/98 (13.3%) | 19/107 (17.8%) | |||
| Urinary tract infection | 4/53 (7.5%) | 3/98 (3.1%) | 8/107 (7.5%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/53 (0%) | 4/98 (4.1%) | 7/107 (6.5%) | |||
| Rheumatoid arthritis | 1/53 (1.9%) | 5/98 (5.1%) | 10/107 (9.3%) | |||
| Nervous system disorders | ||||||
| Headache | 5/53 (9.4%) | 9/98 (9.2%) | 9/107 (8.4%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 0/53 (0%) | 6/98 (6.1%) | 5/107 (4.7%) | |||
| Oropharyngeal pain | 0/53 (0%) | 5/98 (5.1%) | 4/107 (3.7%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 1/53 (1.9%) | 4/98 (4.1%) | 9/107 (8.4%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
- 20070301