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Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis (PREMIER)

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ClinicalTrials.gov Identifier: NCT00195663
Recruitment Status : Completed
First Posted : September 20, 2005
Results First Posted : February 25, 2010
Last Update Posted : July 12, 2013
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Brief Summary:
The purpose of the study is to assess the safety and efficacy of adalimumab in combination with methotrexate in patients with recent onset rheumatoid arthritis (RA), and to assess the long-term safety and maintenance of efficacy after treatment with adalimumab for up to 10 years.

Condition or disease Intervention/treatment Phase
Early Rheumatoid Arthritis Biological: Adalimumab Drug: Methotrexate Biological: Adalimumab placebo Drug: Methotrexate placebo Phase 3

Detailed Description:
This study had an initial 2-year double-blind treatment period followed by an 8-year open-label extension period, for a total of up to 10 years study duration. The study was designed to assess the potential of adalimumab + methotrexate to improve signs and symptoms of disease and to inhibit radiographic progression in patients with recent onset (disease duration less than 3 years) rheumatoid arthritis not previously treated with methotrexate. Adalimumab is a human anti-tumor necrosis factor (TNF) monoclonal antibody.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 799 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFα Antibody Adalimumab Given Every Second Week With Methotrexate Given Weekly and the Combination of Adalimumab and Methotrexate Administered Over 2 Years in Patients With Early Rheumatoid Arthritis (PREMIER).
Study Start Date : December 2000
Actual Primary Completion Date : April 2004
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Adalimumab
Participants received adalimumab 40 mg subcutaneous injection once every other week and placebo to methotrexate orally once a week during the 2-year double-blind treatment phase and then adalimumab 40 mg every other week for up to 8 years in the open-label extension.
Biological: Adalimumab
Other Names:
  • ABT-D2E7
  • Humira

Drug: Methotrexate placebo
Experimental: Adalimumab + methotrexate
Participants received adalimumab 40 mg subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.
Biological: Adalimumab
Other Names:
  • ABT-D2E7
  • Humira

Drug: Methotrexate
Experimental: Methotrexate
Participants received placebo to adalimumab subcutaneous injection once every other week and methotrexate orally once a week at a starting dose of 7.5 mg/week (could be escalated up to 20 mg/week) during the 2-year double-blind treatment phase. Participants received adalimumab 40 mg every other week for up to 8 years in the open-label extension phase.
Drug: Methotrexate
Biological: Adalimumab placebo



Primary Outcome Measures :
  1. Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52 [ Time Frame: Baseline and 52 Weeks ]

    American College of Rheumatology 50% (ACR50) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (HAQ-DI));
      • Acute phase reactant value (C-Reactive Protein).

    Participants who withdrew early were considered non-responders.


  2. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52 [ Time Frame: Baseline and Week 52 ]
    The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 52 were scored in a blinded manner. 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 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.


Secondary Outcome Measures :
  1. Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52 [ Time Frame: Baseline and Week 52 ]
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.

  2. Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 104 [ Time Frame: Baseline and Week 104 ]

    American College of Rheumatology 50% (ACR50) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Participants withdrawing early were considered non-responders.


  3. Change From Baseline in Modified Total Sharp Score (mTSS) at Week 104 [ Time Frame: Baseline and Week 104 ]
    The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and Week 104 were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  4. Number of Participants Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at Week 52 [ Time Frame: Week 52 ]
    The DAS28 is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C reactive protein, and general health were included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.

  5. Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36) at Week 52 [ Time Frame: Baseline and Week 52 ]
    The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.

  6. Number of Participants With Major Clinical Response After 104 Weeks of Treatment [ Time Frame: Any 6 continuous months from Baseline to Week 104 ]

    Major clinical response was defined as an American College of Rheumatology 70% (ACR70) response for any six continuous months, over 104 weeks of treatment. A participant was a responder if the following 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Participants withdrawing early were non-responders.


  7. Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36) at Week 52 [ Time Frame: Baseline and Week 52 ]
    The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.

  8. Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Weeks 26 and 76 [ Time Frame: Baseline and Weeks 26 and 76 ]

    American College of Rheumatology 50% (ACR50) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Participants withdrawing early were considered non-responders.


  9. Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria During the Double-blind Phase [ Time Frame: Baseline and Weeks 26, 52, 76, and 104 ]

    American College of Rheumatology 20% (ACR20) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Participants withdrawing early were considered non-responders.


  10. Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria During the Double-blind Phase [ Time Frame: Baseline and Weeks 26, 52, 76, and 104 ]

    American College of Rheumatology 70% (ACR70) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Participants withdrawing early were considered non-responders.


  11. Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 12, 26, 76, and 104 ]
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.

  12. Number of Participants With Improvement in the HAQ-DI Score ≥ 0.3 During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 26, 52, 76, and 104 ]
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability.

  13. Change From Baseline in Health Utilities Index Mark 2 and Mark 3 (HUI 2/3) During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 26, 52, and 104 ]

    The HUI 2/3 is an assessment of various aspects of participants' health and ability to perform various tasks on a day-to-day basis, including reading, seeing, hearing, speaking, general outlook on life, pain/discomfort, ability to walk, use of hands, memory, ability to think/solve, and ability to perform basic activities such as eating, bathing, and dressing. The HUI 2/3 is a combined 15-item questionnaire based on a recall period of the previous 4 weeks. HUI-2 and HUI-3 scores are calculated independently. The HUI-2 score includes 6 attributes: Sensation, Mobility, Emotion, Cognition, Self-Care, and Pain. The HUI-3 score is comprised of 8 attributes: Vision, Hearing, Speech, Ambulation, Dexterity, Emotion, Cognition, and Pain.

    The range of each score is from 0 (dead) to 1 (perfect health). An increase from Baseline indicates improvement.


  14. Change From Baseline in the Short Form-36 Health Status Survey (SF-36) During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 26 and 104 ]
    The SF-36 determined participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 comprise the physical component and items 5-8 comprise the mental component of the SF-36. Scores on each item were summed and averaged (range = 0-100); increases from Baseline indicate improvement.

  15. Numeric American College of Rheumatology (ACR-N) During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 26, 52, 76, and 104 ]
    ACR-N is a composite, continuous variable which measures the percentage of improvement from Baseline in individual participants based on the 7 core set variables of the ACR. ACR-N is defined as the smallest percent change from Baseline of 3 measures: tender joint counts (TJC), swollen joint counts (SJC), and the median percent improvement in the 5 remaining measures (Patient's Assessment of Pain, Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity, Health Assessment Questionnaire - Disability Index [HAQ-DI], and C-Reactive Protein). A positive ACR-N value indicates improvement; a negative ACR-N value indicates worsening; ACR-N of 0 indicates no change.

  16. Change From Baseline in Disease Activity Score (DAS28) During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 26, 52, 76, and 104 ]

    The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

    • 28 tender joint counts,
    • 28 swollen joint counts,
    • C-reactive protein, and
    • Patient's global assessment of disease activity.

    Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  17. Change From Baseline in Joint Erosion Score During the Double-blind Treatment Period [ Time Frame: Baseline and Weeks 52 and 104 ]
    Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints on each hand/wrist (17 joints) and each forefoot (6 joints) were scored for erosions on a scale of 0 = no erosions; 1 = 1 discrete erosion or ≤20% joint involvement; 2 = 2 separate quadrants with erosion or 21-40% joint involvement; 3 = 3 separate quadrants with erosion or 41-60% joint involvement; 4 = all 4 quadrants with erosion or 61-80% joint involvement; and 5 = extensive destruction with >80% joint involvement. Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion)to 230 (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.

  18. Change From Baseline in Joint Space Narrowing Score During the Double-blind Treatment Period [ Time Frame: Baseline and Weeks 52 and 104 ]
    Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joint space narrowing (JSN) scores were recorded for each hand/wrist (16 joints) and each forefoot (5 joints) on a 5-point scale (0 = no narrowing; 1 = up to 25% narrowing; 2 = 26-65% narrowing; 3 = 66-99% narrowing; and 4 = complete narrowing). Scores were summed to calculate the total score ranging from 0 (no narrowing) to 168 (maximum narrowing). A large increase in joint narrowing score is indicative of worsening, whereas a small change or no change is indicative of inhibition of JSN.

  19. Number of Participants With No Worsening in Modified Total Sharp Score or Components During the Double-blind Treatment Phase [ Time Frame: Baseline and Weeks 52 and 104 ]

    The number of participants with no worsening in the modified Total Sharp Score (mTSS) and in erosion and joint space narrowing (JSN) scores, where no worsening is defined as a change from Baseline of ≤ 0 in mTSS, erosion score and JSN score, at Weeks 52 and 104.

    Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.


  20. Number of Participants With No Erosions at Baseline and No New Erosions at Weeks 52 and 104 [ Time Frame: Baseline and Weeks 52 and 104 ]

    The number of participants with no erosions at Baseline and no erosions at Weeks 52 and 104, where no erosions and no new erosions are defined as an erosion score = 0.

    Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints on each hand/wrist (17 joints) and each forefoot (6 joints) were scored for erosions on a scale of 0 = no erosions; 1 = 1 discrete erosion or ≤20% joint involvement; 2 = 2 separate quadrants with erosion or 21-40% joint involvement; 3 = 3 separate quadrants with erosion or 41-60% joint involvement; 4 = all 4 quadrants with erosion or 61-80% joint involvement; and 5 = extensive destruction with >80% joint involvement. Scores were summed to calculate the total erosion score, which ranges from 0 (no erosion) to 230 (worst).


  21. Number of Participants With Non-Involved Joints at Baseline and No Newly Involved Joints at Weeks 52 and 104 [ Time Frame: Baseline and Weeks 52 and 104 ]

    Number of participants with non-involved joints at Baseline and no newly involved joints at Weeks 52 and 104, where involved joints or no newly involved joints are defined as modified Total Sharp Score (mTSS) = 0.

    Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]).


  22. Number of Participants Meeting ACR20 Response Criteria Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab. ]

    American College of Rheumatology 20% (ACR20) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Baseline is the last value prior to the first dose of adalimumab. For participants randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.


  23. Number of Participants Meeting ACR50 Response Criteria Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab. ]

    American College of Rheumatology 50% (ACR50) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Baseline is the last value prior to the first dose of adalimumab. For patients randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.


  24. Number of Participants Meeting ACR70 Response Criteria Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab. ]

    American College of Rheumatology 70% (ACR70) response. 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

    Baseline is the last value prior to the first dose of adalimumab. For patients randomized to the methotrexate (MTX) arm in the double-blind (DB) phase, Baseline was the last visit prior to the first adalimumab dose at Week 106 of the open-label (OL) phase.


  25. Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106. ]
    The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. Negative mean changes from Baseline in the overall score indicate improvement.

  26. Change From Baseline in DAS28 Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106. ]

    The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

    • 28 tender joint counts,
    • 28 swollen joint counts,
    • C-reactive protein, and
    • Patient's global assessment of disease activity.

    Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  27. Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by Adalimumab Exposure [ Time Frame: After 1, 2, 5, and 10 years of adalimumab exposure ]

    The DAS28 is a composite score of rheumatoid arthritis disease activity derived from the following variables:

    • 28 tender joint counts,
    • 28 swollen joint counts,
    • C-reactive protein, and
    • Patient's global assessment of disease activity.

    Scores on the DAS28 range from 0 to 10. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score less than 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.


  28. Change From Baseline in Modified Total Sharp Score (mTSS) Over 10 Years [ Time Frame: Baseline (prior to first study drug treatment) and Years 2 and 10 ]
    The modified TSS (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement.

  29. Number of Participants With No Radiographic Progression Over 10 Years [ Time Frame: Baseline (prior to first study drug treatment) and Years 2 and 10. ]
    The modified Total Sharp Score (mTSS) is a measure of change in joint health. Digitized images of radiographs of hands and feet obtained at screening and during the study were scored in a blinded manner. Joints were scored for erosions on a scale of 0 (no damage) to 5 (complete collapse) and joint space narrowing on a scale of 0 (no damage) to 4 (ankylosis or complete dislocation). Erosion scores and narrowing scores were added to obtain the mTSS (range = 0 [normal] to 398 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening, no change represents halting of disease progression, and a decrease represents improvement. The number of participants with change from Baseline ≤ 0.5 and ≤ 0 is reported as a measure of no disease progression.

  30. Composite Score of ACR50 Plus No Change in Modified Total Sharp Score [ Time Frame: Year 10 ]
  31. Number of Participants With a Major Clinical Response Over 10 Years by Adalimumab Exposure [ Time Frame: From the first dose of adalimumab (at Week 1 or Week 106 for patients initially randomized to methotrexate in the DB phase) to Year 10 ]

    A major clinical response was defined as maintenance of an ACR70 response for at least a 6-month continuous period at any time during the study following the first dose of adalimumab. A participant was a responder if the following 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:

      • Patient's assessment of pain (measured on a 100 mm visual analog scale [VAS]);
      • Patient's global assessment of disease activity (measured on a 100 mm VAS);
      • Physician's global assessment of disease activity (measured on a 100 mm VAS);
      • Patient's self-assessment of physical function (Health Assessment Questionnaire - Disability Index [HAQ-DI]);
      • Acute phase reactant value (C-Reactive Protein).

  32. Number of Participants With Improvement in HAQ-DI by 0.22 and 0.5 Units Over 10 Years by Adalimumab Exposure [ Time Frame: Baseline and Years 1, 2, 5, and 10. Baseline was the last value prior to the first dose of adalimumab. For patients randomized to the MTX arm in the DB phase, Baseline was the last visit prior to the first adalimumab dose at Week 106. ]
    The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. A decrease in the HAQ-DI score represents an improvement in physical function; a clinically significant improvement is defined as a decrease of least 0.22 from Baseline in the HAQ-DI score. The number of participants with improvement in HAQ-DI of at least 0.22 and 0.5 units from Baseline is reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subject was age 18 or older and in good health (Investigator discretion) with a recent stable medical history.
  • Diagnosis of rheumatoid arthritis (RA) as defined by the 1987-revised American College of Rheumatology (ACR) criteria, with a disease duration less than 3 years, at least 8 swollen joints out of the 66 joints assessed, at least 10 tender joints out of the 68 joints assessed, at least 1 joint erosion or rheumatoid factor (RF) positivity, erythrocyte sedimentation rate (ESR) >= 28 mm/1h or C-reactive protein (CRP) >= 1.5 mg/dl

Exclusion Criteria:

  • Chronic arthritis diagnosed before the age of 16
  • Preceding treatment with MTX, cyclophosphamide, cyclosporin, azathioprine or more than 2 other disease-modifying anti-rheumatic drugs (DMARDs)
  • Subject previously received anti-tumor necrosis factor (TNF) therapy
  • Permanently wheelchair-bound or bedridden patients
  • Subject considered by the investigator, for any reason, to be an unsuitable candidate for the study
  • Female subject who is pregnant or breast-feeding or considering becoming pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00195663


  Show 123 Study Locations
Sponsors and Collaborators
AbbVie (prior sponsor, Abbott)
Investigators
Study Director: Dawn Carlson AbbVie

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: AbbVie (prior sponsor, Abbott)
ClinicalTrials.gov Identifier: NCT00195663     History of Changes
Other Study ID Numbers: DE013
First Posted: September 20, 2005    Key Record Dates
Results First Posted: February 25, 2010
Last Update Posted: July 12, 2013
Last Verified: June 2013

Keywords provided by AbbVie ( AbbVie (prior sponsor, Abbott) ):
Early Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Adalimumab
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Inflammatory Agents