AB0496 Efficacy of Tofacitinib in Combination with Methotrexate Compared to Biological Disease Modifying Antirheumatic Drugs in Combination with Methotrexate in Rheumatoid Arthritis Patients with an Inadequate Response to Methotrexate: Overview of Systematic Review

BackgroundTofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). JAKs are intracellular enzymes which transmit signals that influence hematopoiesis and immune cell function through phosphorylate and activate the signal transducers and activators of transcription (STATs), which modulate intracellular activity including gene expression. Tofacitinib modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of JAKs. It is a new alternative of biological treatment and its results had been demonstrated in six clinical trials.ObjectivesTo assess the efficacy of tofacitinib in combination with methotrexate compared with biological disease modifying antirheumatic drugs (bDMARDs) in combination with methotrexate, in RA patients with an inadequate response to methotrexate.MethodsWe performed an analysis of systematic reviews published in the last five years that assessed bDMARDs (adalimumab, certolizumab, infliximab, etanercept, golimumab, tocilizumab, rituximab and abatacept) or tofacitinib for the treatment of RA after an inadequate response to methotrexate. The search was conducted within Medline, EMBASE, Cochrane, LILACS, DARE and HTA. The data collection was performed by two researchers independently. Clinical trials that included in the systematic reviews were extracted and evaluated for methodological quality using the Cochrane checklist. The effectiveness of bDMARDs and tofacitinib was compared with a mixed treatment comparison using methotrexate as a common comparator. The outcomes considered in terms of effectiveness were improvements in ACR20, ACR50, and ACR70 rates and HAQ criteria at 12 and 24 weeks. In order to evaluate the impact of heterogeneity, we performed an analysis of sensibility and subgroups.Results27 systematic reviews were included, in which 30 clinical trials were assessed and analyzed. The indirect comparison showed that tofacitinib has similar efficacy in comparison to bDMARDs in ACR20, ACR50, ACR70 rates and improvements in HAQ at 12 and 24 weeks. However, certolizumab demonstrated a better response that tofacitinib in ACR20 at 12 weeks (odds ratio 0.373; 95% confidence interval 0.201 – 0.615). The sensitivity and subgroup analyses, which were analyzed by clinical trial design, disease duration and number of swollen joints, showed consistent results.ConclusionsThe mixed treatment comparison indicated that tofacitinib is similar in terms of efficacy to