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Center for Global Research Data

Effect of rheumatoid factor and anticitrullinated peptide antibody on the efficacy of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis

Lead Investigator: Diane van der Woude, Leiden University Medical Center
Title of Proposal Research: Effect of rheumatoid factor and anticitrullinated peptide antibody on the efficacy of biological disease-modifying antirheumatic drugs in patients with rheumatoid arthritis
Vivli Research Request: 4922, 3274
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Biological disease-modifying antirheumatic drugs (bDMARDs) have significantly improved clinical outcomes of rheumatoid arthritis (RA) patients. However, the association between the presence of autoantibodies and efficacy of bDMARDs has not yet been thoroughly studied.

The purpose of this study is to investigate the role of autoantibodies in the response to bDMARDs. More specifically we aim at understanding whether there is a different efficacy of bDMARDs in seropositive patients compared to seronegative patients.

We are conducting a systematic literature review, if possible complemented by a meta-analysis. Randomized controlled trials (RCTs) have been identified through previous systematic literature reviews addressing the efficacy of bDMARDs to inform the EULAR recommendations for the management of RA. Data will be collected into a standardized data extraction sheet.
Studies that included both autoantibody-positive and negative patients (with the percentage of seropositive patients being ≤80%) fulfilling the 1987 or 2010 RA criteria will be eligible. Interventions considered will be on-label dose of bDMARDs and any comparator. Strategy trials will not be included.

The primary endpoint is the American College of Rheumatology 20% improvement criteria (ACR20) response at 6 months. Secondary endpoints are the change in the Disease Activity Score 28-joint count with erythrocyte sedimentation rate (DAS28-ESR), American College of Rheumatology 50% improvement criteria (ACR50) response, American College of Rheumatology 70% improvement criteria (ACR70) response, achievement of remission, change in the Health Assessment Questionnaire (HAQ), and progression in total Sharp (van der Heijde) score, at 6 months. All endpoints will be analyzed in subgroups of patients according to baseline auto-antibody status. This amounts to 1 primary and 6 secondary endpoints, which is much more limited and reasonable. We will also look at the outcomes at 12 and 24 months, but not statistically test them as those outcomes are assessed in the long-term extension period, i.e. without a formal comparator, as there is no placebo.

The first step is to collect the above-mentioned endpoints stratified for baseline auto-antibody status. We are also requesting the data of other RCTs addressing the efficacy of bDMARDs. Having all data, we will conduct a meta-analysis of RCTs.

Requested Studies:

Safety Trial of Adalimumab in Rheumatoid Arthritis (Abbott STAR trial)
Sponsor: AbbVie
Sponsor ID: DE031

A Randomized, Double-Blind, Placebo-Controlled, Phase III Study of the Human Anti-TNF Antibody Adalimumab Administered as Subcutaneous Injections in Korean Rheumatoid Arthritis Subjects Treated With Methotrexate
Sponsor: AbbVie
Study ID: NCT00235859
Sponsor ID: M02-556

(Note: Additional studies added as part of Data Request 4922)

A DOUBLE-BLIND STUDY EVALUATING THE EFFICACY AND SAFETY OF THE COMBINATION OF ETANERCEPT AND METHOTREXATE IN COMPARISON TO ETANERCEPT ALONE OR METHOTREXATE ALONE IN RHEUMATOID ARTHRITIS PATIENTS (TEMPO)
Data Contributor: Pfizer Inc.
Study ID: NCT00393471 (Pfizer Protocol ID: B1801240)

A 24-MONTH, RANDOMIZED, DOUBLE-BLIND, TWO-PERIOD STUDY TO EVALUATE THE EFFICACY AND SAFETY OF THE COMBINATION OF ETANERCEPT AND METHOTREXATE AND METHOTREXATE ALONE IN SUBJECTS WITH ACTIVE EARLY RHEUMATOID ARTHRITIS (COMET)
Data Contributor: Pfizer Inc.
Study ID: NCT00195494 (Pfizer ID: B1801325)

A-6-MONTH, DOUBLE-BLIND COMPARISON OF ETANERCEPT, SULPHASALAZINE, AND THE COMBINATION OF ETANERCEPT (COMBE)
Data Contributor: Pfizer Inc.
Study ID: Legacy Wyeth Study 0881A1-309- No NCT# (Pfizer ID: B1801241)

STUDY EVALUATING THE EFFICACY AND SAFETY OF ETANERCEPT AND METHOTREXATE IN JAPANESE SUBJECTS WITH RHEUMATOID ARTHRITIS (TAKEUCHI)
Data Contributor: Pfizer Inc.
Study ID: NCT00445770 (Pfizer Protocol ID: B1801002)