SAT0178 Clinical Responses of Sarilumab Based on Rheumatoid Factor and Anti–Cyclic Citrullinated Peptide Antibody Status in Patients with Rheumatoid Arthritis
Authors: P. Emery, H. van Hoogstraten, E.K. Mangan, J. van Adelsberg, C. Fan, A. Kivitz, G.da R.C. Pinheiro, T. Huizinga
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Sarilumab is a human investigational anti–IL-6 receptor mAb that has been studied in 2 randomized, double-blind, placebo-controlled, multicenter, phase 3 studies in patients with RA. Subcutaneous (SC) sarilumab q2w + MTX demonstrated efficacy in patients with inadequate response to MTX in the MOBILITY study (NCT01061736).<sup>1</sup> Sarilumab SC q2w + conventional synthetic DMARDs demonstrated efficacy in patients who were inadequate responders to or intolerant of TNFi in the TARGET study (NCT01709578).<sup>2</sup> The most common TEAEs in both studies were infections, neutropenia, injection site reactions, and increased transaminases. <h3>Objectives</h3> Negative autoantibody status has been associated with attenuated clinical response to biologic disease-modifying agents in RA.<sup>3,4</sup> This study assessed the clinical efficacy of sarilumab in subgroups of patients based on rheumatoid factor (RF) and anti-CCP antibody status in MOBILITY and TARGET. <h3>Methods</h3> Incidence of ACR20/50/70 response at wk 24, mean change from baseline in HAQ-DI at wk 12 (TARGET) or 16 (MOBILITY), and DAS28-CRP at wk 24 were evaluated by RF and CCP status. <h3>Results</h3> The majority of MOBILITY (78%) and TARGET (70%) patients were RF+/CCP+. Treatment-by-subgroup interaction (<i>P</i>&lt;0.05) was observed for ACR20 response (CCP status in MOBILITY; RF and CCP in TARGET) and HAQ-DI (RF and CCP status in MOBILITY; RF in TARGET). Clinical and functional responses in RF/CCP single- and double-positive patients were generally similar to overall study results (Table). However, certain clinical measures, including HAQ-DI, showed a trend toward smaller effect sizes, particularly in double-negative patients, that was somewhat more pronounced with sarilumab 150 mg q2w (Table), though sample sizes were small. Comparable findings were observed for DAS28-CRP: mean change from baseline for placebo + MTX, sarilumab 150 mg q2w + MTX, and sarilumab 200 mg q2w + MTX was -1.56 (n=191), -2.75 (n=257), and -3.09 (n=246), respectively, for RF+/CCP+ patients and -1.97 (n=22), -2.10 (n=13), and -2.51 (n=20), respectively, for RF-/CCP- patients in MOBILITY. TARGET results were similar. Trends toward lower clinical and functional responses with RF or CCP negative autoantibody were not observed in radiographic measurements of structural progression; change from baseline in mTSS appeared to be similar regardless of autoantibody status (data on file). <h3>Conclusions</h3> Overall, within MOBILITY and TARGET, clinical responses with sarilumab were generally consistent among patients who were RF+ and/or CCP+. Regardless of autoantibody status, there was a more robust response with regard to clinical signs and symptoms with sarilumab 200 mg q2w. <h3>References</h3> Genovese et al. Arthritis Rheumatol. 2015;67:1424–1437 Fleischmann et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA Alten et al. Presented at: ACR; November 7–11, 2015; San Francisco, CA Chatzidionysiou et al. Ann Rheum Dis. 2011;70:1575–1580 <h3>Acknowledgement</h3> This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Editorial assistance was provided by Rebecca Slager, PhD, MS, MedThink SciCom, and funded by Sanofi and Regeneron Pharmaceuticals, Inc. <h3>Disclosure of Interest</h3> P. Emery Consultant for: AbbVie, Bristol-Myers Squibb, Lilly, MSD, Novartis, Pfizer, Roche, Samsung, Sandoz, and UCB, H. van Hoogstraten Shareholder of: Sanofi, Employee of: Sanofi, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, J. van Adelsberg Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, C. Fan Shareholder of: Sanofi, Employee of: Sanofi, A. Kivitz Consultant for: Sanofi, Pfizer, Roche, and UCB, G. da R.C. Pinheiro Consultant for: AbbVie, AstraZeneca, GlaxoSmithKline, Hospira, Janssen, Pfizer, Roche, RuiYi, and Sanofi, T. Huizinga Consultant for: Sanofi