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

Primary Purpose

Early Rheumatoid Arthritis

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Adalimumab

Methotrexate

Adalimumab placebo

Methotrexate placebo

About this trial

This is an interventional treatment trial for Early Rheumatoid Arthritis focused on measuring Early Rheumatoid Arthritis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Adalimumab

Adalimumab + methotrexate

Methotrexate

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase

Number of Participants With Improvement in the HAQ-DI Score ≥ 0.3 During the Double-blind Treatment Phase

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.

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.

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.

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.

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.

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.

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.

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).

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]).

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.

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.

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.

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure

Change From Baseline in DAS28 Over 10 Years by Adalimumab Exposure

Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by Adalimumab Exposure

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.

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.

Composite Score of ACR50 Plus No Change in Modified Total Sharp Score

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).

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.

Full Information

NCT ID

NCT00195663

First Posted

September 13, 2005

Last Updated

June 7, 2013

Sponsor

AbbVie (prior sponsor, Abbott)

1. Study Identification

Unique Protocol Identification Number

NCT00195663

Brief Title

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

Acronym

PREMIER

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 Type

Interventional

2. Study Status

Record Verification Date

June 2013

Overall Recruitment Status

Completed

Study Start Date

December 2000 (undefined)

Primary Completion Date

April 2004 (Actual)

Study Completion Date

April 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AbbVie (prior sponsor, Abbott)

4. Oversight

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Early Rheumatoid Arthritis

Keywords

Early Rheumatoid Arthritis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

799 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Adalimumab

Arm Type

Experimental

Arm Description

Arm Title

Adalimumab + methotrexate

Arm Type

Experimental

Arm Description

Arm Title

Methotrexate

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Adalimumab

Other Intervention Name(s)

ABT-D2E7, Humira

Intervention Type

Drug

Intervention Name(s)

Methotrexate

Intervention Type

Biological

Intervention Name(s)

Adalimumab placebo

Intervention Type

Drug

Intervention Name(s)

Methotrexate placebo

Primary Outcome Measure Information:

Title

Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 52

Description

Time Frame

Baseline and 52 Weeks

Title

Change From Baseline in Modified Total Sharp Score (mTSS) at Week 52

Description

Time Frame

Baseline and Week 52

Secondary Outcome Measure Information:

Title

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52

Description

Time Frame

Baseline and Week 52

Title

Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Week 104

Description

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.

Time Frame

Baseline and Week 104

Title

Change From Baseline in Modified Total Sharp Score (mTSS) at Week 104

Description

Time Frame

Baseline and Week 104

Title

Number of Participants Who Achieved Clinical Remission, Defined as a Disease Activity 28 (DAS28) Score < 2.6 at Week 52

Description

Time Frame

Week 52

Title

Change From Baseline in the Physical Component of the Short Form-36 Health Status Survey (SF-36) at Week 52

Description

Time Frame

Baseline and Week 52

Title

Number of Participants With Major Clinical Response After 104 Weeks of Treatment

Description

Time Frame

Any 6 continuous months from Baseline to Week 104

Title

Change From Baseline in the Mental Component of the Short Form-36 Health Status Survey (SF-36) at Week 52

Description

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.

Time Frame

Baseline and Week 52

Title

Number of Participants Meeting American College of Rheumatology 50% (ACR50) Response Criteria at Weeks 26 and 76

Description

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.

Time Frame

Baseline and Weeks 26 and 76

Title

Number of Participants Meeting American College of Rheumatology 20% (ACR20) Response Criteria During the Double-blind Phase

Description

Time Frame

Baseline and Weeks 26, 52, 76, and 104

Title

Number of Participants Meeting American College of Rheumatology 70% (ACR70) Response Criteria During the Double-blind Phase

Description

Time Frame

Baseline and Weeks 26, 52, 76, and 104

Title

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 12, 26, 76, and 104

Title

Number of Participants With Improvement in the HAQ-DI Score ≥ 0.3 During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 26, 52, 76, and 104

Title

Change From Baseline in Health Utilities Index Mark 2 and Mark 3 (HUI 2/3) During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 26, 52, and 104

Title

Change From Baseline in the Short Form-36 Health Status Survey (SF-36) During the Double-blind Treatment Phase

Description

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.

Time Frame

Baseline and Weeks 26 and 104

Title

Numeric American College of Rheumatology (ACR-N) During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 26, 52, 76, and 104

Title

Change From Baseline in Disease Activity Score (DAS28) During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 26, 52, 76, and 104

Title

Change From Baseline in Joint Erosion Score During the Double-blind Treatment Period

Description

Time Frame

Baseline and Weeks 52 and 104

Title

Change From Baseline in Joint Space Narrowing Score During the Double-blind Treatment Period

Description

Time Frame

Baseline and Weeks 52 and 104

Title

Number of Participants With No Worsening in Modified Total Sharp Score or Components During the Double-blind Treatment Phase

Description

Time Frame

Baseline and Weeks 52 and 104

Title

Number of Participants With No Erosions at Baseline and No New Erosions at Weeks 52 and 104

Description

Time Frame

Baseline and Weeks 52 and 104

Title

Number of Participants With Non-Involved Joints at Baseline and No Newly Involved Joints at Weeks 52 and 104

Description

Time Frame

Baseline and Weeks 52 and 104

Title

Number of Participants Meeting ACR20 Response Criteria Over 10 Years by Adalimumab Exposure

Description

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.

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.

Title

Number of Participants Meeting ACR50 Response Criteria Over 10 Years by Adalimumab Exposure

Description

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.

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.

Title

Number of Participants Meeting ACR70 Response Criteria Over 10 Years by Adalimumab Exposure

Description

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.

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.

Title

Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Over 10 Years by Adalimumab Exposure

Description

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.

Title

Change From Baseline in DAS28 Over 10 Years by Adalimumab Exposure

Description

Time Frame

Title

Number of Participants With DAS28 < 2.6 and < 3.2 Over 10 Years by Adalimumab Exposure

Description

Time Frame

After 1, 2, 5, and 10 years of adalimumab exposure

Title

Change From Baseline in Modified Total Sharp Score (mTSS) Over 10 Years

Description

Time Frame

Baseline (prior to first study drug treatment) and Years 2 and 10

Title

Number of Participants With No Radiographic Progression Over 10 Years

Description

Time Frame

Baseline (prior to first study drug treatment) and Years 2 and 10.

Title

Composite Score of ACR50 Plus No Change in Modified Total Sharp Score

Time Frame

Year 10

Title

Number of Participants With a Major Clinical Response Over 10 Years by Adalimumab Exposure

Description

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

Title

Number of Participants With Improvement in HAQ-DI by 0.22 and 0.5 Units Over 10 Years by Adalimumab Exposure

Description

Time Frame

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dawn Carlson

Organizational Affiliation

AbbVie

Official's Role

Study Director

Facility Information:

Facility Name

Site Reference ID/Investigator# 322

City

Scottsdale

State/Province

Arizona

ZIP/Postal Code

85260

Country

United States

Facility Name

Site Ref # / Investigator 95957

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

Site Reference ID/Investigator# 429

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

Site Reference ID/Investigator# 2491

City

Los Angeles

State/Province

California

ZIP/Postal Code

90048

Country

United States

Facility Name

Site Reference ID/Investigator# 2500

City

Denver

State/Province

Colorado

ZIP/Postal Code

80230

Country

United States

Facility Name

Site Reference ID/Investigator# 762

City

Aventura

State/Province

Florida

ZIP/Postal Code

33180

Country

United States

Facility Name

Site Reference ID/Investigator# 328

City

Sarasota

State/Province

Florida

ZIP/Postal Code

34239

Country

United States

Facility Name

Site Reference ID/Investigator# 327

City

Tampa

State/Province

Florida

ZIP/Postal Code

33614

Country

United States

Facility Name

Site Reference ID/Investigator# 325

City

Zephyrhills

State/Province

Florida

ZIP/Postal Code

33542

Country

United States

Facility Name

Site Reference ID/Investigator# 302

City

Rockford

State/Province

Illinois

ZIP/Postal Code

61103

Country

United States

Facility Name

Site Reference ID/Investigator# 319

City

Cumberland

State/Province

Maryland

ZIP/Postal Code

21502

Country

United States

Facility Name

Site Ref # / Investigator 95960

City

Hagerstown

State/Province

Maryland

ZIP/Postal Code

21740

Country

United States

Facility Name

Site Reference ID/Investigator# 326

City

Wheaton

State/Province

Maryland

ZIP/Postal Code

20902

Country

United States

Facility Name

Site Reference ID/Investigator# 2533

City

Worcester

State/Province

Massachusetts

ZIP/Postal Code

01605-0000

Country

United States

Facility Name

Site Reference ID/Investigator# 336

City

Lincoln

State/Province

Nebraska

ZIP/Postal Code

68516

Country

United States

Facility Name

Site Reference ID/Investigator# 318

City

Concord

State/Province

New Hampshire

ZIP/Postal Code

03301

Country

United States

Facility Name

Site Reference ID/Investigator# 488

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27704

Country

United States

Facility Name

Site Reference ID/Investigator# 314

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45408

Country

United States

Facility Name

Site Reference ID/Investigator# 761

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73103

Country

United States

Facility Name

Site Reference ID/Investigator# 757

City

Eugene

State/Province

Oregon

ZIP/Postal Code

97401

Country

United States

Facility Name

Site Reference ID/Investigator# 361

City

Lake Oswego

State/Province

Oregon

ZIP/Postal Code

97035

Country

United States

Facility Name

Site Reference ID/Investigator# 316

City

Bethlehem

State/Province

Pennsylvania

ZIP/Postal Code

18015

Country

United States

Facility Name

Site Reference ID/Investigator# 4649

City

Duncansville

State/Province

Pennsylvania

ZIP/Postal Code

16635

Country

United States

Facility Name

Site Ref # / Investigator 96122

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Site Reference ID/Investigator# 306

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Site Reference ID/Investigator# 313

City

Austin

State/Province

Texas

ZIP/Postal Code

78705

Country

United States

Facility Name

Site Reference ID/Investigator# 2437

City

Dallas

State/Province

Texas

ZIP/Postal Code

75231

Country

United States

Facility Name

Site Reference ID/Investigator# 2532

City

Houston

State/Province

Texas

ZIP/Postal Code

77074

Country

United States

Facility Name

Site Reference ID/Investigator# 758

City

Houston

State/Province

Texas

ZIP/Postal Code

77074

Country

United States

Facility Name

Site Reference ID/Investigator# 321

City

Spokane

State/Province

Washington

ZIP/Postal Code

99204

Country

United States

Facility Name

Site Reference ID/Investigator# 305

City

Yakima

State/Province

Washington

ZIP/Postal Code

98902

Country

United States

Facility Name

Site Reference ID/Investigator# 310

City

Brisbane

ZIP/Postal Code

4102

Country

Australia

Facility Name

Site Reference ID/Investigator# 755

City

Camperdown

ZIP/Postal Code

2050

Country

Australia

Facility Name

Site Reference ID/Investigator# 337

City

Clayton

ZIP/Postal Code

3168

Country

Australia

Facility Name

Site Reference ID/Investigator# 331

City

Darlinghurst, Sydney

ZIP/Postal Code

2010

Country

Australia

Facility Name

Site Reference ID/Investigator# 745

City

Kogarah

ZIP/Postal Code

2217

Country

Australia

Facility Name

Site Reference ID/Investigator# 738

City

Maroochydore

ZIP/Postal Code

4558

Country

Australia

Facility Name

Site Reference ID/Investigator# 335

City

New Lambton

ZIP/Postal Code

2305

Country

Australia

Facility Name

Site Reference ID/Investigator# 737

City

Shenton Park

ZIP/Postal Code

6008

Country

Australia

Facility Name

Site Reference ID/Investigator# 307

City

South Hobart

ZIP/Postal Code

7004

Country

Australia

Facility Name

Site Reference ID/Investigator# 427

City

West Heidelberg

ZIP/Postal Code

3081

Country

Australia

Facility Name

Site Reference ID/Investigator# 739

City

Woodville

ZIP/Postal Code

5011

Country

Australia

Facility Name

Site Reference ID/Investigator# 344

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

Site Reference ID/Investigator# 753

City

Brussels

ZIP/Postal Code

1070

Country

Belgium

Facility Name

Site Reference ID/Investigator# 308

City

Brussels

ZIP/Postal Code

1090

Country

Belgium

Facility Name

Site Reference ID/Investigator# 752

City

Brussels

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Site Reference ID/Investigator# 748

City

Diepenbeek

ZIP/Postal Code

3590

Country

Belgium

Facility Name

Site Reference ID/Investigator# 6136

City

Ghent

ZIP/Postal Code

9000

Country

Belgium

Facility Name

Site Ref # / Investigator 98256

City

Leuven

ZIP/Postal Code

3000

Country

Belgium

Facility Name

Site Reference ID/Investigator# 333

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Site Ref # / Investigator 98199

City

North York

State/Province

Ontario

ZIP/Postal Code

M3H 5Y8

Country

Canada

Facility Name

Site Reference ID/Investigator# 4646

City

Edmonton

ZIP/Postal Code

T6G 2S2

Country

Canada

Facility Name

Site Reference ID/Investigator# 303

City

Hamilton

ZIP/Postal Code

L8N 1Y2

Country

Canada

Facility Name

Site Reference ID/Investigator# 330

City

Hamilton

ZIP/Postal Code

L8N 2B6

Country

Canada

Facility Name

Site Reference ID/Investigator# 4634

City

Montreal

ZIP/Postal Code

H2L 1S6

Country

Canada

Facility Name

Site Reference ID/Investigator# 311

City

Montreal

ZIP/Postal Code

H3Z 2Z3

Country

Canada

Facility Name

Site Reference ID/Investigator# 309

City

Newmarket

ZIP/Postal Code

L3Y 3R7

Country

Canada

Facility Name

Site Reference ID/Investigator# 304

City

Pointe-Claire

ZIP/Postal Code

H9J 3W3

Country

Canada

Facility Name

Site Reference ID/Investigator# 4633

City

Richmond

ZIP/Postal Code

V7C 5L9

Country

Canada

Facility Name

Site Reference ID/Investigator# 763

City

St. John's

ZIP/Postal Code

A1A 5E8

Country

Canada

Facility Name

Site Reference ID/Investigator# 4635

City

Toronto

ZIP/Postal Code

M4N 3M5

Country

Canada

Facility Name

Site Reference ID/Investigator# 490

City

Toronto

ZIP/Postal Code

M5L 3L9

Country

Canada

Facility Name

Site Reference ID/Investigator# 760

City

Victoria

ZIP/Postal Code

V8V 3P9

Country

Canada

Facility Name

Site Reference ID/Investigator# 4632

City

Winnipeg

ZIP/Postal Code

R3N OK6

Country

Canada

Facility Name

Site Reference ID/Investigator# 754

City

Hradec Kralove

ZIP/Postal Code

500 05

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 332

City

Plzen

ZIP/Postal Code

305 99

Country

Czech Republic

Facility Name

Site Reference ID/Investigator# 734

City

Prague 2

ZIP/Postal Code

128 50

Country

Czech Republic

Facility Name

Site Ref # / Investigator 95878

City

Grasten

ZIP/Postal Code

6300

Country

Denmark

Facility Name

Site Reference ID/Investigator# 6135

City

Heinola

ZIP/Postal Code

FI-18120

Country

Finland

Facility Name

Site Ref # / Investigator 6134

City

Helsinki

ZIP/Postal Code

00029

Country

Finland

Facility Name

Site Reference ID/Investigator# 428

City

Bobigny

ZIP/Postal Code

93009

Country

France

Facility Name

Site Reference ID/Investigator# 348

City

Montpellier Cedex 5

ZIP/Postal Code

34295

Country

France

Facility Name

Site Reference ID/Investigator# 4650

City

Paris Cedex 14

ZIP/Postal Code

75679

Country

France

Facility Name

Site Reference ID/Investigator# 3415

City

Pierre Benite

ZIP/Postal Code

69310

Country

France

Facility Name

Site Reference ID/Investigator# 733

City

Rennes

ZIP/Postal Code

35056

Country

France

Facility Name

Site Reference ID/Investigator# 346

City

Strasbourg, Cedex 1

ZIP/Postal Code

67098

Country

France

Facility Name

Site Reference ID/Investigator# 3417

City

Berlin-Buch

ZIP/Postal Code

13125

Country

Germany

Facility Name

Site Reference ID/Investigator# 4631

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Site Reference ID/Investigator# 759

City

Berlin

ZIP/Postal Code

14059

Country

Germany

Facility Name

Site Reference ID/Investigator# 4630

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Site Reference ID/Investigator# 347

City

Freiburg

ZIP/Postal Code

79106

Country

Germany

Facility Name

Site Reference ID/Investigator# 742

City

Goerlitz

ZIP/Postal Code

02826

Country

Germany

Facility Name

Site Reference ID/Investigator# 746

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Site Ref # / Investigator 98125

City

Munich

ZIP/Postal Code

80336

Country

Germany

Facility Name

Site Reference ID/Investigator# 339

City

Munich

ZIP/Postal Code

80336

Country

Germany

Facility Name

Site Reference ID/Investigator# 744

City

Ratingen

ZIP/Postal Code

40882

Country

Germany

Facility Name

Site Reference ID/Investigator# 338

City

Vogelsang-Gommern

ZIP/Postal Code

39245

Country

Germany

Facility Name

Site Reference ID/Investigator# 740

City

Cork

ZIP/Postal Code

WDQ-23-KM9

Country

Ireland

Facility Name

Site Reference ID/Investigator# 751

City

Dublin 4

Country

Ireland

Facility Name

Site Ref # / Investigator 95719

City

Genoa

ZIP/Postal Code

16132

Country

Italy

Facility Name

Site Reference ID/Investigator# 323

City

Naples

ZIP/Postal Code

80131

Country

Italy

Facility Name

Site Reference ID/Investigator# 345

City

Udine

ZIP/Postal Code

33100

Country

Italy

Facility Name

Site Reference ID/Investigator# 756

City

Verona

ZIP/Postal Code

37134

Country

Italy

Facility Name

Site Reference ID/Investigator# 343

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Site Reference ID/Investigator# 6133

City

Leiden

ZIP/Postal Code

2333 ZA

Country

Netherlands

Facility Name

Site Reference ID/Investigator# 317

City

Maastricht

ZIP/Postal Code

6229 HX

Country

Netherlands

Facility Name

Site Reference ID/Investigator# 315

City

Nijmegen

ZIP/Postal Code

6500 HB

Country

Netherlands

Facility Name

Site Ref # / Investigator 95800

City

Osla

ZIP/Postal Code

0027

Country

Norway

Facility Name

Site Ref # / Investigator 95875

City

Osla

ZIP/Postal Code

0370

Country

Norway

Facility Name

Site Reference ID/Investigator# 3426

City

Piestany

ZIP/Postal Code

92112

Country

Slovakia

Facility Name

Site Ref # / Investigator 96121

City

Alicante

ZIP/Postal Code

03010

Country

Spain

Facility Name

Site Reference ID/Investigator# 735

City

Alicante

ZIP/Postal Code

03010

Country

Spain

Facility Name

Site Reference ID/Investigator# 1525

City

Barcelona

ZIP/Postal Code

08036

Country

Spain

Facility Name

Site Reference ID/Investigator# 1528

City

Barcelona

ZIP/Postal Code

08915

Country

Spain

Facility Name

Site Reference ID/Investigator# 750

City

Guadalajara

ZIP/Postal Code

19002

Country

Spain

Facility Name

Site Reference ID/Investigator# 1526

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Site Reference ID/Investigator# 741

City

Madrid

ZIP/Postal Code

28040

Country

Spain

Facility Name

Site Reference ID/Investigator# 390

City

Santiago de Compostela

ZIP/Postal Code

15706

Country

Spain

Facility Name

Site Reference ID/Investigator# 749

City

Sevilla

ZIP/Postal Code

41014

Country

Spain

Facility Name

Site Reference ID/Investigator# 728

City

Stockholm

ZIP/Postal Code

113 24

Country

Sweden

Facility Name

Site Reference ID/Investigator# 2565

City

Stockholm

ZIP/Postal Code

171 76

Country

Sweden

Facility Name

Site Reference ID/Investigator# 4638

City

Stockholm

ZIP/Postal Code

SE-141 86

Country

Sweden

Facility Name

Site Ref # / Investigator 96126

City

Umea

ZIP/Postal Code

901 84

Country

Sweden

Facility Name

Site Reference ID/Investigator# 747

City

Uppsala

ZIP/Postal Code

75185

Country

Sweden

Facility Name

Site Ref # / Investigator 96120

City

Vasteras

ZIP/Postal Code

S-721 89

Country

Sweden

Facility Name

Site Reference ID/Investigator# 736

City

Vasteras

ZIP/Postal Code

S-721 89

Country

Sweden

Facility Name

Site Reference ID/Investigator# 334

City

Lausanne

ZIP/Postal Code

1011

Country

Switzerland

Facility Name

Site Ref # / Investigator 96116

City

Bangor

ZIP/Postal Code

LL57 2PW

Country

United Kingdom

Facility Name

Site Ref # / Investigator 95877

City

Cambridge

ZIP/Postal Code

CB2 0QQ

Country

United Kingdom

Facility Name

Site Ref # / Investigator 98258

City

Hereford

ZIP/Postal Code

HR1 2ER

Country

United Kingdom

Facility Name

Site Ref # / Investigator 95795

City

Leeds

ZIP/Postal Code

LS1 3EX

Country

United Kingdom

Facility Name

Site Ref # / Investigator 95958

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Site Ref # / Investigator 98255

City

Newcastle upon Tyne

ZIP/Postal Code

NE7 7DN

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

31707982

Citation

Smolen J, Fleischmann R, Aletaha D, Li Y, Zhou Y, Sainsbury I, Galindo IL. Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials. Arthritis Res Ther. 2019 Nov 10;21(1):231. doi: 10.1186/s13075-019-2005-9.

Results Reference

derived

PubMed Identifier

30076156

Citation

Smolen JS, van Vollenhoven RF, Florentinus S, Chen S, Suboticki JL, Kavanaugh A. Predictors of disease activity and structural progression after treatment with adalimumab plus methotrexate or continued methotrexate monotherapy in patients with early rheumatoid arthritis and suboptimal response to methotrexate. Ann Rheum Dis. 2018 Nov;77(11):1566-1572. doi: 10.1136/annrheumdis-2018-213502. Epub 2018 Aug 3.

Results Reference

derived

PubMed Identifier

29955381

Citation

Keystone EC, Breedveld FC, Kupper H, Li Y, Florentinus S, Sainsbury I. Long-term use of adalimumab as monotherapy after attainment of low disease activity with adalimumab plus methotrexate in patients with rheumatoid arthritis. RMD Open. 2018 Jun 13;4(1):e000637. doi: 10.1136/rmdopen-2017-000637. eCollection 2018.

Results Reference

derived

PubMed Identifier

29018564

Citation

Keystone EC, Breedveld FC, van der Heijde D, van Vollenhoven RF, Emery P, Smolen JS, Sainsbury I, Florentinus S, Kupper H, Chen K, Kavanaugh A. Achieving comprehensive disease control in patients with early and established rheumatoid arthritis treated with adalimumab plus methotrexate versus methotrexate alone. RMD Open. 2017 Sep 26;3(2):e000445. doi: 10.1136/rmdopen-2017-000445. eCollection 2017.

Results Reference

derived

PubMed Identifier

28950430

Citation

Moller B, Everts-Graber J, Florentinus S, Li Y, Kupper H, Finckh A. Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial. Arthritis Care Res (Hoboken). 2018 Jun;70(6):861-868. doi: 10.1002/acr.23427. Epub 2018 Apr 25.

Results Reference

derived

PubMed Identifier

27338778

Citation

Burmester GR, Landewe R, Genovese MC, Friedman AW, Pfeifer ND, Varothai NA, Lacerda AP. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2017 Feb;76(2):414-417. doi: 10.1136/annrheumdis-2016-209322. Epub 2016 Jun 23.

Results Reference

derived

PubMed Identifier

25994819

Citation

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

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

Early Rheumatoid Arthritis

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