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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00195663




Registration number
NCT00195663
Ethics application status
Date submitted
13/09/2005
Date registered
20/09/2005
Date last updated
12/07/2013

Titles & IDs
Public title
Efficacy and Safety of Adalimumab and Methotrexate (MTX) Versus MTX Monotherapy in Subjects With Early Rheumatoid Arthritis
Scientific title
A Prospective Multi-Centre Randomised, Double-Blind, Active Comparator-Controlled, Parallel-Groups Study Comparing the Fully Human Monoclonal Anti-TNFa 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).
Secondary ID [1] 0 0
DE013
Universal Trial Number (UTN)
Trial acronym
PREMIER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Early Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Adalimumab
Treatment: Drugs - Methotrexate
Other interventions - Adalimumab placebo
Treatment: Drugs - Methotrexate placebo

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.

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.

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.


Other interventions: Adalimumab


Treatment: Drugs: Methotrexate


Other interventions: Adalimumab placebo


Treatment: Drugs: Methotrexate placebo


Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52 - 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.
Timepoint [1] 0 0
Baseline and 52 Weeks
Primary outcome [2] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at 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.
Timepoint [2] 0 0
Baseline and Week 52
Secondary outcome [1] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at 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.
Timepoint [1] 0 0
Baseline and Week 52
Secondary outcome [2] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at 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.
Timepoint [2] 0 0
Baseline and Week 104
Secondary outcome [3] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) at 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.
Timepoint [3] 0 0
Baseline and Week 104
Secondary outcome [4] 0 0
Number of Participants Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at 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.
Timepoint [4] 0 0
Week 52
Secondary outcome [5] 0 0
Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36) at 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.
Timepoint [5] 0 0
Baseline and Week 52
Secondary outcome [6] 0 0
Number of Participants With Major Clinical Response After 104 Weeks of Treatment - 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.
Timepoint [6] 0 0
Any 6 continuous months from Baseline to Week 104
Secondary outcome [7] 0 0
Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36) at 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.
Timepoint [7] 0 0
Baseline and Week 52
Secondary outcome [8] 0 0
Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at 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.
Timepoint [8] 0 0
Baseline and Weeks 26 and 76
Secondary outcome [9] 0 0
Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria During the Double-blind Phase - 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.
Timepoint [9] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [10] 0 0
Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria During the Double-blind Phase - 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.
Timepoint [10] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [11] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase - 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.
Timepoint [11] 0 0
Baseline and Weeks 12, 26, 76, and 104
Secondary outcome [12] 0 0
Number of Participants With Improvement in the HAQ-DI Score = 0.3 During the Double-blind Treatment Phase - 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.
Timepoint [12] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [13] 0 0
Change From Baseline in Health Utilities Index Mark 2 and Mark 3 (HUI 2/3) During the Double-blind Treatment Phase - 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.
Timepoint [13] 0 0
Baseline and Weeks 26, 52, and 104
Secondary outcome [14] 0 0
Change From Baseline in the Short Form-36 Health Status Survey (SF-36) During the Double-blind Treatment Phase - 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.
Timepoint [14] 0 0
Baseline and Weeks 26 and 104
Secondary outcome [15] 0 0
Numeric American College of Rheumatology (ACR-N) During the Double-blind Treatment Phase - 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.
Timepoint [15] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [16] 0 0
Change From Baseline in Disease Activity Score (DAS28) During the Double-blind Treatment Phase - 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.
Timepoint [16] 0 0
Baseline and Weeks 26, 52, 76, and 104
Secondary outcome [17] 0 0
Change From Baseline in Joint Erosion Score During the Double-blind Treatment Period - 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.
Timepoint [17] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [18] 0 0
Change From Baseline in Joint Space Narrowing Score During the Double-blind Treatment Period - 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.
Timepoint [18] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [19] 0 0
Number of Participants With No Worsening in Modified Total Sharp Score or Components During the Double-blind Treatment Phase - 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.
Timepoint [19] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [20] 0 0
Number of Participants With No Erosions at Baseline and No New Erosions at 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).
Timepoint [20] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [21] 0 0
Number of Participants With Non-Involved Joints at Baseline and No Newly Involved Joints at 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]).
Timepoint [21] 0 0
Baseline and Weeks 52 and 104
Secondary outcome [22] 0 0
Number of Participants Meeting ACR20 Response Criteria Over 10 Years by Adalimumab Exposure - 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.
Timepoint [22] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [23] 0 0
Number of Participants Meeting ACR50 Response Criteria Over 10 Years by Adalimumab Exposure - 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.
Timepoint [23] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [24] 0 0
Number of Participants Meeting ACR70 Response Criteria Over 10 Years by Adalimumab Exposure - 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.
Timepoint [24] 0 0
Baseline and after 1, 2, 5, and 10 years of adalimumab exposure. Baseline was the last value prior to the first dose of adalimumab.
Secondary outcome [25] 0 0
Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure - 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.
Timepoint [25] 0 0
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.
Secondary outcome [26] 0 0
Change From Baseline in DAS28 Over 10 Years by 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.
Timepoint [26] 0 0
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.
Secondary outcome [27] 0 0
Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by 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.
Timepoint [27] 0 0
After 1, 2, 5, and 10 years of adalimumab exposure
Secondary outcome [28] 0 0
Change From Baseline in Modified Total Sharp Score (mTSS) Over 10 Years - 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.
Timepoint [28] 0 0
Baseline (prior to first study drug treatment) and Years 2 and 10
Secondary outcome [29] 0 0
Number of Participants With No Radiographic Progression Over 10 Years - 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.
Timepoint [29] 0 0
Baseline (prior to first study drug treatment) and Years 2 and 10.
Secondary outcome [30] 0 0
Composite Score of ACR50 Plus No Change in Modified Total Sharp Score
Timepoint [30] 0 0
Year 10
Secondary outcome [31] 0 0
Number of Participants With a Major Clinical Response Over 10 Years by Adalimumab Exposure - 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).
Timepoint [31] 0 0
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
Secondary outcome [32] 0 0
Number of Participants With Improvement in HAQ-DI by 0.22 and 0.5 Units Over 10 Years by Adalimumab Exposure - 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.
Timepoint [32] 0 0
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.

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Site Reference ID/Investigator# 310 - Brisbane
Recruitment hospital [2] 0 0
Site Reference ID/Investigator# 755 - Camperdown
Recruitment hospital [3] 0 0
Site Reference ID/Investigator# 337 - Clayton
Recruitment hospital [4] 0 0
Site Reference ID/Investigator# 331 - Darlinghurst, Sydney
Recruitment hospital [5] 0 0
Site Reference ID/Investigator# 745 - Kogarah
Recruitment hospital [6] 0 0
Site Reference ID/Investigator# 738 - Maroochydore
Recruitment hospital [7] 0 0
Site Reference ID/Investigator# 335 - New Lambton
Recruitment hospital [8] 0 0
Site Reference ID/Investigator# 737 - Shenton Park
Recruitment hospital [9] 0 0
Site Reference ID/Investigator# 307 - South Hobart
Recruitment hospital [10] 0 0
Site Reference ID/Investigator# 427 - West Heidelberg
Recruitment hospital [11] 0 0
Site Reference ID/Investigator# 739 - Woodville
Recruitment postcode(s) [1] 0 0
4102 - Brisbane
Recruitment postcode(s) [2] 0 0
2050 - Camperdown
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst, Sydney
Recruitment postcode(s) [5] 0 0
2217 - Kogarah
Recruitment postcode(s) [6] 0 0
4558 - Maroochydore
Recruitment postcode(s) [7] 0 0
2305 - New Lambton
Recruitment postcode(s) [8] 0 0
6008 - Shenton Park
Recruitment postcode(s) [9] 0 0
7004 - South Hobart
Recruitment postcode(s) [10] 0 0
3081 - West Heidelberg
Recruitment postcode(s) [11] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Maryland
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Nebraska
Country [9] 0 0
United States of America
State/province [9] 0 0
New Hampshire
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oklahoma
Country [13] 0 0
United States of America
State/province [13] 0 0
Oregon
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Austria
State/province [17] 0 0
Vienna
Country [18] 0 0
Belgium
State/province [18] 0 0
Brussels
Country [19] 0 0
Belgium
State/province [19] 0 0
Diepenbeek
Country [20] 0 0
Belgium
State/province [20] 0 0
Ghent
Country [21] 0 0
Belgium
State/province [21] 0 0
Leuven
Country [22] 0 0
Belgium
State/province [22] 0 0
Liege
Country [23] 0 0
Canada
State/province [23] 0 0
Ontario
Country [24] 0 0
Canada
State/province [24] 0 0
Edmonton
Country [25] 0 0
Canada
State/province [25] 0 0
Hamilton
Country [26] 0 0
Canada
State/province [26] 0 0
Montreal
Country [27] 0 0
Canada
State/province [27] 0 0
Newmarket
Country [28] 0 0
Canada
State/province [28] 0 0
Pointe-Claire
Country [29] 0 0
Canada
State/province [29] 0 0
Richmond
Country [30] 0 0
Canada
State/province [30] 0 0
St. John's
Country [31] 0 0
Canada
State/province [31] 0 0
Toronto
Country [32] 0 0
Canada
State/province [32] 0 0
Victoria
Country [33] 0 0
Canada
State/province [33] 0 0
Winnipeg
Country [34] 0 0
Czech Republic
State/province [34] 0 0
Hradec Kralove
Country [35] 0 0
Czech Republic
State/province [35] 0 0
Plzen
Country [36] 0 0
Czech Republic
State/province [36] 0 0
Prague 2
Country [37] 0 0
Denmark
State/province [37] 0 0
Grasten
Country [38] 0 0
Finland
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Heinola
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Finland
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Helsinki
Country [40] 0 0
France
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Bobigny
Country [41] 0 0
France
State/province [41] 0 0
Montpellier Cedex 5
Country [42] 0 0
France
State/province [42] 0 0
Paris Cedex 14
Country [43] 0 0
France
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Pierre Benite
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France
State/province [44] 0 0
Rennes
Country [45] 0 0
France
State/province [45] 0 0
Strasbourg, Cedex 1
Country [46] 0 0
Germany
State/province [46] 0 0
Berlin-Buch
Country [47] 0 0
Germany
State/province [47] 0 0
Berlin
Country [48] 0 0
Germany
State/province [48] 0 0
Erlangen
Country [49] 0 0
Germany
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Freiburg
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Germany
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Goerlitz
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Germany
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Leipzig
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Germany
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Munich
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Germany
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Ratingen
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Germany
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Vogelsang-Gommern
Country [55] 0 0
Ireland
State/province [55] 0 0
Cork
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Ireland
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Dublin 4
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Italy
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Genoa
Country [58] 0 0
Italy
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Naples
Country [59] 0 0
Italy
State/province [59] 0 0
Udine
Country [60] 0 0
Italy
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Verona
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Netherlands
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Groningen
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Netherlands
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Leiden
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Netherlands
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Maastricht
Country [64] 0 0
Netherlands
State/province [64] 0 0
Nijmegen
Country [65] 0 0
Norway
State/province [65] 0 0
Osla
Country [66] 0 0
Slovakia
State/province [66] 0 0
Piestany
Country [67] 0 0
Spain
State/province [67] 0 0
Alicante
Country [68] 0 0
Spain
State/province [68] 0 0
Barcelona
Country [69] 0 0
Spain
State/province [69] 0 0
Guadalajara
Country [70] 0 0
Spain
State/province [70] 0 0
Madrid
Country [71] 0 0
Spain
State/province [71] 0 0
Santiago de Compostela
Country [72] 0 0
Spain
State/province [72] 0 0
Sevilla
Country [73] 0 0
Sweden
State/province [73] 0 0
Stockholm
Country [74] 0 0
Sweden
State/province [74] 0 0
Umea
Country [75] 0 0
Sweden
State/province [75] 0 0
Uppsala
Country [76] 0 0
Sweden
State/province [76] 0 0
Vasteras
Country [77] 0 0
Switzerland
State/province [77] 0 0
Lausanne
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Bangor
Country [79] 0 0
United Kingdom
State/province [79] 0 0
Cambridge
Country [80] 0 0
United Kingdom
State/province [80] 0 0
Hereford
Country [81] 0 0
United Kingdom
State/province [81] 0 0
Leeds
Country [82] 0 0
United Kingdom
State/province [82] 0 0
London
Country [83] 0 0
United Kingdom
State/province [83] 0 0
Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie (prior sponsor, Abbott)
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00195663
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Dawn Carlson
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications