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

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

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 European League Against Rheumatism (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 previous (1987) and the new (2010) RA classification criteria will be eligible. The classification criteria for RA were set up in 1987 and these were replaced in 2010. 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% response (ACR20) at 6 months. The ACR20 is a standard criteria to measure the effectiveness of various arthritis medications or treatments in clinical trials for RA. Secondary endpoints are the change in the Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), American College of Rheumatology 50% response (ACR50), American College of Rheumatology 70% response (ACR70), achievement of remission, change in Health Assessment Questionnaire Disability Index (HAQ-DI) score, and radiographic progression measured by total Sharp (van der Heijde) score, at 6 months. All endpoints will be analyzed in subgroups of patients according to baseline auto-antibody status. The same outcomes at 12 and at 24 months will be also analyzed whether there is a sustainability of response, but not compared to placebo as there is no placebo-controlled arm beyond 6 months.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.

[{ "PostingID": 1350, "Title": "ROCHE-WA17822", "Description": "A randomized, double-blind study of safety and reduction in signs and symptoms during treatment with tocilizumab versus placebo, in combination with methotrexate, in patients with moderate to severe rheumatoid arthritis" },{ "PostingID": 1352, "Title": "ROCHE-WA17824", "Description": "A randomized, double-blind study of safety and reduction in signs and symptoms during treatment with tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe active rheumatoid arthritis" },{ "PostingID": 1353, "Title": "ROCHE-WA18062", "Description": "A randomized, double-blind study of safety and reduction in signs and symptoms during treatment with tocilizumab versus placebo, in combination with methotrexate, in patients with moderate to severe active rheumatoid arthritis and inadequate response to anti-TNF therapy" },{ "PostingID": 1354, "Title": "ROCHE-WA18063", "Description": "A randomized, double-blind study of the effect of tocilizumab on reduction in signs and symptoms in patients with moderate to severe active rheumatoid arthritis and inadequate response to DMARD therapy" },{ "PostingID": 1360, "Title": "ROCHE-MRA012JP", "Description": "A phase III randomised, parallel-group study of MRA in patients with rheumatoid arthritis" },{ "PostingID": 2647, "Title": "ROCHE-WA19924", "Description": "A Multi-center, Randomized, Blinded, Parallel-group Study of the Reduction of Signs and Symptoms During Monotherapy Treatment With Tocilizumab 8 mg/kg Intravenously Versus Adalimumab 40 mg Subcutaneously in Patients With Rheumatoid Arthritis" },{ "PostingID": 3685, "Title": "ROCHE-WA17042", "Description": "A Phase IIb Randomized, Multifactorial, Double-Blind, Parallel Group, Dose Ranging Study of the Efficacy and Safety of Rituximab (MabThera/Rituxan) in Combination with Methotrexate, in Patients with active Rheumatoid Arthritis" },{ "PostingID": 3687, "Title": "ROCHE-WA17045", "Description": "A randomized, double-blind study to evaluate the effect on treatment response of MabThera in combination with methotrexate, compared to methotrexate monotherapy, in patients with active rheumatoid arthritis" },{ "PostingID": 19791, "Title": "ROCHE-ML21136", "Description": "A randomized, double-blind, parallel-group study to evaluate the safety and efficacy of tocilizumab (TCZ) versus placebo in combination with disease modifying antirheumatic drugs (DMARDs) in patients with moderate to severe active rheumatoid arthritis (RA)" }]