SAT0167 Comparison of the efficacy and tolerability of tocilizumab, sarilumab, and sirukumab in patients with active rheumatoid arthritis: a bayesian network meta-analysis of randomized controlled trials

Background: A humanized, anti-human IL-6 receptor monoclonal antibody, tocilizumab, was developed to block IL-6 signaling and has been used as an effective therapeutic agent for patients that do not respond to methotrexate (MTX) or tumor necrosis factor (TNF) inhibitor. The successful use of tocilizumab in RA stimulated the development of other biologics targeted to the IL-6 pathway, such as anti-IL-6R (sarilumab) or anti-IL-6 (sirukumab) antibodies. Objectives: The relative efficacy and tolerability of tocilizumab, sarilumab, and sirukumab were assessed in patients with rheumatoid arthritis (RA) and an inadequate response to MTX or TNF inhibitors. Methods: We performed a Bayesian network meta-analysis to combine direct and indirect evidence from randomized controlled trials (RCTs) to examine the efficacy and safety of tocilizumab, sarilumab, and sirukumab in RA patients and an inadequate MTX or TNF inhibitor response. Results: Fourteen RCTs, comprising 9,753 patients, met the inclusion criteria. Tocilizumab 8 mg combined with MTX or as monotherapy was the most effective treatment for active RA with an inadequate MTX or TNF antagonist response, followed by sarilumab and sirukumab, regardless of MTX combination. The ranking probability based on the surface under the cumulative ranking curve (SUCRA) indicated that tocilizumab 8 mg+MTX had the highest probability of being the best treatment to achieve the ACR50 response rate, followed by tocilizumab 8 mg, sarilumab 200 mg, sarilumab 200 mg+MTX, sirukumab 100 mg, tocilizumab 4 mg+MTX, sirukumab 100 mg+MTX, sirukumab 50 mg+MTX, sarilumab 150 mg+MTX, adalimumab 40 mg, and sirukumab 50 mg, and placebo+MTX. No significant differences were observed in withdrawals owing to adverse events after treatment with tocilizumab 8 mg+MTX, sirukumab 100 mg+MTX, or sarilumab 200 mg+MTX. Conclusions: In RA patients with an inadequate MTX or anti-TNF therapy response, tocilizumab 8 mg as monotherapy and combined with MTX showed acceptable tolerability and the highest performance based on the ACR50 response rate, followed by sarilumab and sirukumab. References [1]Smolen JS, Beaulieu A, Rubbert-Roth A, Ramos-Remus C, Rovensky J, Alecock E, Woodworth T, Alten R, Investigators O. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. The Lancet2008;371:987–997. [2]Genovese M, Fleischmann R, Fiore S, Radin A, Fan C, Huizinga T. SAT0117 Sarilumab, a Subcutaneously-Administered, Fully-Human Monoclonal Antibody Inhibitor of The IL-6 Receptor: Relationship Between Eular Responses and Change from Baseline of Selected Clinical Parameters. Annals of the Rheumatic Diseases2013;72:A620-A620. [3]Xu Z, Bouman-Thio E, Comisar C, Frederick B, Van Hartingsveldt B, Marini JC, Davis HM, Zhou H. Pharmacokinetics, pharmacodynamics and safety of a human anti-IL-6 monoclonal antibody (sirukumab) in healthy subjects in a first-in-human study. British journal of clinical pharmacology2011;72:270–281. Disclosure of Interest: None declared