Evaluating Etanercept Use in Patients With Moderate to Severe Rheumatoid Arthritis Who Have Lost Response to Adalimumab

Phase 4

Terminated

Conditions: Moderate to Severe Rheumatoid Arthritis

Interventions: Biological: Etanercept
Drug: Methotrexate

Registration Number: NCT01927757

Lead Sponsor: Amgen

Brief Summary: To evaluate the efficacy of etanercept in adults with moderate-to-severe rheumatoid arthritis (RA) who did not respond to or lost a satisfactory response to adalimumab when used as their first biologic agent.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 90

Inclusion Criteria

Able to provide informed consent
Diagnosed with moderate to severe rheumatoid arthritis for at least 6 months
Active RA with at least 3 swollen and tender joints
Failure to respond to a combination treatment of adalimumab and methotrexate (must have taken combination at least 3 months) or loss of a satisfactory response to the combination of adalimumab and methotrexate, which was taken for at least 6 months (if currently taking adalimumab must complete 2 weeks without it prior to starting study drug)
Negative for hepatitis B and C
Negative serum and urine pregnancy tests before starting study
currently taking (stable dose) 15 mg methotrexate weekly for at least 8 weeks/has been taking methotrexate for at least 12 weeks total - lower dose of 10 mg per week is permitted with documented intolerability
Normal chest X-ray within 3 months
Negative testing for tuberculosis (TB)

Exclusion Criteria

Class IV RA (wheel-chair or bed-bound)
Significant concurrent medical conditions, including: (uncontrolled type 1 diabetes, poorly controlled type 2 diabetes, symptomatic heart failure, myocardial infarction in past year, history of unstable angina within past year, uncontrolled hypertension, severe chronic pulmonary disease, major chronic inflammatory or connective tissue disease other than RA, Multiple sclerosis, active malignancy, or history of cancer, alcoholic hepatitis or history of alcoholic liver disease)
Other inclusion/exclusion criteria may apply

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Etanercept	Etanercept	Participants received etanercept 50 mg administered subcutaneously once a week with methotrexate for 24 weeks
Etanercept	Methotrexate	Participants received etanercept 50 mg administered subcutaneously once a week with methotrexate for 24 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Week 12	Baseline and Week 12	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With an ACR 20 Response at Week 12 by Anti-adalimumab Antibody Subgroup	Baseline and Week 12	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.
Percentage of Participants With DAS 28-CRP < 3.2	Weeks 12 and 24	The DAS28-CRP 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; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores less than 3.2 are considered low disease activity.
Percentage of Participants With an ACR 20 Response at Week 12 by Response Failure Type Subgroup	Baseline and Week 12	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.
Percentage of Participants With an ACR 20 Response at Week 24	Baseline and Week 24	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 20% improvement in tender joint count; • ≥ 20% improvement in swollen joint count; and • ≥ 20% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.
Percentage of Participants With an ACR 50 Response at Weeks 12 and 24	Baseline and Weeks 12 and 24	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 50% improvement in tender joint count; • ≥ 50% improvement in swollen joint count; and • ≥ 50% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.
Percentage of Participants With an ACR 70 Response at Weeks 12 and 24	Baseline and Weeks 12 and 24	A participant was a responder if the following 3 criteria for improvement from Baseline were met: • ≥ 70% improvement in tender joint count; • ≥ 70% improvement in swollen joint count; and • ≥ 70% improvement in at least 3 of the 5 following parameters: o Patient Global Assessment of Joint Pain (measured on a 100 mm VAS); o Patient Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Physician Global Assessment of Disease Activity (measured on a horizontal scale from 0 to 100); o Health Assessment Questionnaire - Disability Index (HAQ-DI) scale from 0 to 3, where zero represents no disability and three very severe, high-dependency disability; o C-reactive protein level.
Change From Baseline in Disease Activity Score 28-C-Reactive Protein (DAS28-CRP)	Baseline and weeks 12 and 24	The DAS28-CRP 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; * C-reactive protein (CRP) level * Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores above 5.1 indicate high disease activity. A negative change from baseline indicates improvement.
Percentage of Participants With DAS28-CRP Improvement of ≥ 1.2 Units From Baseline	Baseline and weeks 12 and 24	The DAS28-CRP 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; • C-reactive protein (CRP) level • Patient's global assessment of disease activity assessed on a score from 0 to 100. The DAS28-CRP score ranges from zero up to approximately ten. DAS28-CRP scores above 5.1 indicate high disease activity.
Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI)	Baseline and weeks 12 and 24	The HAQ-DI is a questionnaire on which participants are asked to rate their level of difficulty on daily activities (dressing and grooming, arising, eating, and walking) and personal abilities (hygiene, reach, grip, and activity) as well as their use of aids, devices, or help from another person for these activities and disabilities. Responses are scored from 0 indicating no difficulty to 3 indicating inability to perform a task in that area. The overall score is the average of each of the 8 category scores and ranges from 0 (no disability) to 3 (very severe, high-dependency disability).
Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 12	Baseline and Week 12	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses of each domain, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning.
Change From Baseline in 36-item Short Form Health Survey (SF-36) at Week 24	Baseline and Week 24	The Medical Outcome Study Short Form 36-Item Health Survey, Version 2 (SF-36) is a self-administered instrument that measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). Norm-based scores were used in analyses of each domain, calibrated so that 50 is the average score and the standard deviation equals 10. Higher scores indicate a higher level of functioning.
Work Productivity and Activity Impairment (WPAI)	Baseline, week 12 and week 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.