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Completed

NCT Number: NCT00195702

Efficacy and Safety of Adalimumab in Patients With Active Rheumatoid Arthritis Treated Concomitantly With Methotrexate.

The purpose of the study was to assess the safety, immunogenicity, and clinical efficacy of adalimumab compared with placebo (during double-blind phase) and to to evaluate the long-term safety and maintenance of efficacy following repeated administration of adalimumab (during open-label extension phase) in patients with persistently active rheumatoid arthritis who were receiving concurrent methotrexate therapy.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Site Ref # / Investigator 475, Calgary, Alberta, Canada

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About this study

This was a 10-year study which had an initial 52-week, double-blind, placebo-controlled phase followed by an open-label extension phase up to 9 years in duration. Data were analyzed for the double-blind phase using all patients who were randomized and received at least one dose of study drug through Week 52 and for all patients who received at least one dose of adalimumab during the 10-year study (the Intent-to-Treat [ITT] population).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 18 or older and in good health (Investigator discretion) with a recent stable medical history
  • Met American College of Rheumatology (ACR) criteria for diagnosis of active rheumatoid arthritis (RA) and had at both screening and baseline visits >=6 swollen joints and >=9 tender joints, despite a minimum of 3-months treatment with methotrexate (MTX). (Distal interphalangeal joints [DIPs] were not to be included in joint count for inclusion. The screening and baseline visits could be 3 to 28 days apart for patients not previously receiving disease-modifying anti-rheumatic drugs [DMARDs] other than MTX or 4 to 6 weeks for patients requiring a DMARD washout period.)
  • Insufficient efficacy with MTX 12.5 to 25 mg per week (10 mg per week if MTX intolerant).
  • If patient on a second-line treatment (DMARD) other than MTX, he/she had to discontinue it for at least 28 days before the baseline visit (the washout period).
  • Treatment with oral folic acid 1-3 mg/day or, if appropriate, up to 10 mg leucovorin per week.
  • Both rheumatoid factor positivity and a C-reactive protein value >=1 mg/dL, or at least one joint erosion on X-ray.

Exclusion criteria

  • Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study.
  • Female subject who was pregnant or breast-feeding or considering becoming pregnant.
  • Preceding treatment with any tumor necrosis factor (TNF) antagonist, including adalimumab.
  • Prior exposure to alkylating agents, such as chlorambucil or cyclophosphamide.
  • Intra-articular, intramuscular, or intravenous administration of corticosteroids within 4 weeks prior to the screening visit.
  • Subject was wheelchair bound or bedridden.

Treatment and study plan

Adalimumab

Biological

Self-administered, subcutaneous injection of 20 mg adalimumab (1.6 mL/injection) once weekly (ew) for up to 52 weeks.

Other names: ABT-D2E7, Humira

Placebo

Drug

Self-administered, subcutaneous injection of placebo (1.6 mL/injection) once weekly (ew) for up to 52 weeks.

Primary outcomes

  1. Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 24

    Time frame: Week 24

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  2. Change From Baseline in Modified Total Sharp X-ray Score at Week 52

    Time frame: Baseline and Week 52

    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 52. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

  3. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 52

    Time frame: Baseline and Week 52

    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.

Secondary outcomes

  1. Number of Participants Meeting ACR20 Response Criteria at Week 52

    Time frame: Week 52

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  2. Change From Baseline in Modified Total Sharp X-ray Score at Week 24

    Time frame: Baseline and Week 24

    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 24. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

  3. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 24

    Time frame: Baseline and Week 24

    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from baseline in the disability index of the HAQ indicated improvement.

  4. Maintenance of the Disability Index of the HAQ at Week 52 for Participants Who Were Responders at Week 12 or Week 24

    Time frame: Week 52

    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3) eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores included the following: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Responders had a >= 0.22-unit decrease (improvement) in HAQ scores from baseline to Week 12 or 24.

  5. Maintenance of ACR20 Response at Week 52 for Participants Who Were ACR20 Responders at Week 24

    Time frame: Week 52

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  6. Number of Participants With a Continuous ACR70 Response for 6 Months During 52 Weeks of Treatment

    Time frame: Baseline through Week 52

    Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  7. Time to First Response According to ACR20 Criteria - Number of Participants Meeting ACR20 Criteria for the First Time at Each Time Point

    Time frame: Baseline through Week 52

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  8. Time to First Response According to ACR50 Criteria - Number of Participants Meeting ACR50 Criteria for the First Time at Each Time Point

    Time frame: Baseline through Week 52

    Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  9. Time to First Response According to ACR70 Criteria - Number of Participants Meeting ACR70 Criteria for the First Time at Each Time Point

    Time frame: Baseline through Week 52

    Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein. Patients withdrawing early or receiving additional disease-modifying anti-rheumatic drugs (DMARDs) after Week 16 were non-responders.

  10. Estimated Yearly Progression of Rheumatoid Arthritis

    Time frame: Baseline and Week 52

    Estimated yearly progression was defined as modified total Sharp x-ray score at baseline divided by duration of rheumatoid arthritis disease at baseline. Actual progression during the study was defined as modified total Sharp x-ray score at Week 52 minus modified total Sharp x-ray score at baseline divided by the duration of the study. The range of scores for the modified total Sharp x-ray score was 0 (normal) to 398 (maximal disease).

Other outcomes

  1. Baseline Measure: Gender - Female/Male - for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)

    Time frame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group

    Gender (female/male) recorded at Baseline for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.

  2. Baseline Measure: Age Categories for the Any Adalimumab Through Year 10 Group (Intent-to-Treat)

    Time frame: Baseline for Intent-to-Treat (Any Adalimumab Through Year 10) Group

    Age recorded at Baseline, reported by category, for the Intent-to-Treat population (the Any Adalimumab Through Year 10 group) of the study. This measure was not included in the Baseline Characteristics section due to the difficulty of maintaining correct subject numbers and totals in that section.

  3. Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria at Week 260

    Time frame: Week 260

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  4. Number of Participants Meeting the American College of Rheumatology 20% (ACR20) Response Criteria at Week 520

    Time frame: Week 520

    Patients were responders if they had: >= 20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  5. Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 260

    Time frame: Week 260

    Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  6. Number of Participants Meeting the American College of Rheumatology 50% (ACR50) Response Criteria at Week 520

    Time frame: Week 520

    Patients were responders if they had: >= 50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  7. Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 260

    Time frame: Week 260

    Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  8. Number of Participants Meeting the American College of Rheumatology 70% (ACR70) Response Criteria at Week 520

    Time frame: Week 520

    Patients were responders if they had: >= 70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  9. Number of Participants With a Continuous American College of Rheumatology 70% (ACR70) Response for at Least 6 Months Through Year 10

    Time frame: Baseline through Week 520

    Patients were responders if they had: >=70% improvement in tender joint count; >=70% improvement in swollen joint count; and >=70% improvement in at least 3 of 5 remaining ACR core measures: patient assessment of pain; patient global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and acute phase reactant: C-reactive protein.

  10. Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 260

    Time frame: Week 260

    The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.

  11. Number of Participants With at Least a 0.22 Reduction From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 520

    Time frame: Week 520

    The Health Assessment Questionnaire (HAQ) Disability Index is a self-reported measure of disability, which assesses the patient's ability to perform the following tasks: dress and groom; arise; eat; walk; reach; grip; maintain hygiene; and maintain daily activity. Possible responses/scores are 0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do). Negative mean changes from Baseline indicate improvement. An improvement of 0.22 in score (a -0.22 or greater reduction from Baseline score) is a minimally clinically significant change.

  12. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 260

    Time frame: Baseline and Week 260

    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.

  13. Change From Baseline in the Disability Index of the Health Assessment Questionnaire (HAQ) at Week 520

    Time frame: Baseline and Week 520

    Subjects assessed their ability to perform the following tasks: 1) dress/groom; 2) arise; 3)eat; 4) walk; 5) reach; 6) grip; 7) maintain hygiene; and 8) maintain daily activity. Subjects assessed their ability to do these tasks over the past week by marking their response on a questionnaire. Possible responses/scores were: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Negative mean changes from Baseline in the disability index of the HAQ indicated improvement.

  14. Change From Baseline in Modified Total Sharp X-ray Score at Week 416

    Time frame: Baseline and Week 416

    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 416. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

  15. Change From Baseline in Modified Total Sharp X-ray Score at Week 520

    Time frame: Baseline and Week 520

    Modified total Sharp x-ray score (mTSS) is a measure of change in joint health. Radiographs of hands/wrists and feet were obtained at screening and Week 520. Digitized images of these were scored in a blinded manner. Joints were scored for erosions from 0 (no damage) to 5 and for joint space narrowing from 0 (no damage) to 4; scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). Large positive change indicates disease progression; small positive/no change indicates slowing/halting of disease progression; and negative change may indicate improvement of disease.

Sponsors and collaborators

Lead sponsor

Abbott

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab in Rheumatoid Arthritis Patients Currently Receiving Treatment With Methotrexate

Important dates

Study start
2000
Primary completion
2002
Study completion
2010
First posted
Sep 20, 2005
Registry last updated
Aug 26, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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