CAMEO: Canadian Methotrexate and Etanercept Outcome Study

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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Canadian Methotrexate and Etanercept Outcome Study: An Open Label Randomized Trial of Etanercept and Methotrexate Versus Etanercept Alone in the Treatment of Rheumatoid Arthritis (CAMEO)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: Etanercept
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Etanercept + Methotrexate<br>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<br>* Commercially available etanercept administered subcutaneously at 50 mg/week.<br>* Other names: Enbrel®;Drug: Methotrexate<br>* Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)<br>|
| Experimental: Etanercept Only<br>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<br>* Commercially available etanercept administered subcutaneously at 50 mg/week.<br>* Other names: Enbrel®;Drug: Methotrexate<br>* Commercially available methotrexate administed orally, subcutaneously or intramuscularly 15 mg/week (or 10 mg/week in case of documented intolerance to higher doses)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Month 6 to Month 12 in Disease Activity Sscore 28 (DAS28) | 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. | Month 6 (randomization) and Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Activity Score (DAS) 28 Response | 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. | Month 6, 12, 18 and 24 | 
| Change From Baseline in Disease Activity Score 28 (DAS28) | 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. | Baseline and Month 6, 12, 18 and 24 | 
| Drug Persistence | Drug persistence is defined as the percentage of participants receiving etanercept at 6, 12, 18, and 24 months. | Month 6, 12, 18 and 24 | 
| Change From Baseline in Modified Total Sharp Score (mTSS) | 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. | Baseline, Month 12 and Month 24 | 
| Change From Baseline in Joint Erosion Score | 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. | Baseline, Month 12 and Month 24 | 
| Change From Baseline in Joint Space Narrowing | 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. | Baseline, Month 12 and Month 24 | 
| Change From Month 6 in Health Assessment Questionnaire Disability Index (HAQ DI) | 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. | Month 6, 12, 18 and 24 | 
| Change From Month 6 in Health Assessment Questionnaire Pain Visual Analog Scale (VAS) | 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. | Month 6, 12, 18 and 24 | 
| Change From Month 6 in Short Form 36 Health Survey (SF-36) | 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. | Month 6, 12, 18 and 24 | 
| Change From Month 6 in Work Productivity and Activity Impairment (WPAI) | 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. | Month 6, 12, 18 and 24 | 
| Change From Month 6 in Treatment Satisfaction Questionnaire for Medication (TSQM) | 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. | Month 6, 12, 18 and 24 | 
| Number of Participants With Adverse Events (AEs) | 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. | 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amgen