Abstract
Background:Biologic disease-modifying antirheumatic drugs (bDMARDs) extend the treatment choices for rheumatoid arthritis (RA) patients with suboptimal response or intolerance to conventional synthetic DMARDs (CsDMARDs). Currently, 9 biologic agents are approved in the RA treatment: and among them, three anti TNF agents are also approved in monotherapy (adalimumab, certolizumab and etanercept), but also abatacept, anakinra and tocilizumab. Registries of routine clinical practice treatment indicate that approximately one third of RA patients are being treated with a bDMARD in monotherapy and analyses from health care claims suggest that when methotrexate (MTX) is prescribed in combination with a bDMARD, more than half of the patients do not collect the MTX prescription and overall patients seem to taper MTX intake over time. So it is important to evaluate the benefit and harm associated with use of biological agents as monotherapy, and not only the traditional combination therapy strategies.Objectives:To compare the efficacy and safety of the individual biological agents used in monotherapy in patients with RA than the combination therapy strategy with CsDMARD + bDMARD.Methods:We used The Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, and MEDLINE in order to carry out our research, for published reports from inception of each database through December 2019. Search results were limited to randomised controlled trials (RCTs), with our two arms: biological agent in monotherapy and combination strategie (with any CsDMARDs). Major outcome was the ACR 20 reponse criteria at 24 week. The secondary outcomes were: the ACR 20 at 52 week, ACR 50, 70, 90 reponse criteria, the DAS 28 remission (with CRP and/or ESR), the score sharps modified non progressor, the proportion of patients who withdrawals the study due to adverse events, the proportion of patients who withdrawals the study due to lack of efficacy, the HAQ improvement > 0,22, CDAI and SDAI remission at week 24 and 52 if the data were available. The study of tolerance was also made. To estimate the relative efficacy of treatments whilst preserving the randomized comparisons within each trial, a Bayesian network meta-analysis was conducted in R (version 3.6.1) using fixed and random-effects.Results:The systematic review identified 2566 citations. The analysis comprises 22 trials (6358 patients), including six biological agents approved for RA (abatacept, adalimumab, etanercept, golimumab, rituximab and tocilizumab) as well as two other molecules: Clazakizumab, a humanized monoclonal antibody that binds to the interleukin-6 (IL-6) cytokine and Anbainuo, recombinant human TNFRII:Fc fusion protein. No study satisfyies our search criteria for anakinra, certolizumab and infliximab. Compared to combination therapy with CsDMARD+bDMARD, bDMARD monotherapy has less probability to give a ACR20 response at 24 weeks (RR: 0,92 [0,89 – 0,96]) in fixed or random effect model and this result is similar at 52 weeks (RR: 0,94 [0,89 – 0,99]). For all other outcome mesures, we can see an increased of ACR50–70 and 90 responses, an improve of the DAS 28 remission score, an increase of the proportion of sharp’s score non progressors (<0,5) as well as a decrease of withdrawals for inefficacy without increase of withdrawals for toxicity.Conclusion:Evidence from this meta-analysis suggests that combinaison strategy with bDMARD+CsDMARD remains the most efficacious option, being more effective than the use of biologics in monotherapy. The interest from this point of view is to sensitize prescribers to the use of other CsDMARDs when there is a contraindication or intolerance to MTX, but also to make patients aware of the superiority of the association of biological agents with CsDMARDs.figureDisclosure of Interests:Célia DELPECH: None declared, François-Xavier LABORNE: None declared, Pascal Hilliquin Consultant of: BMS, MSD, Novartis, Roche-Shugai.
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