SAT0183 Switching from adalimumab to sarilumab is associated with comparable efficacy but lower functional improvement versus continuous sarilumab monotherapy through 48-week open-label extension (OLE) of the phase 3 monarch trial
Authors: G. R. Burmester, G. St John, M. Iglesias-Rodriguez, C.-C. Hu, T. Raskina, H. Amital, A. Gomez Centeno, A. Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background:</h3> Sarilumab is a human mAb blocking IL-6Rα. In Phase 3 MONARCH (NCT02332590), sarilumab (200 mg subcutaneously [SC] every 2 wks [q2w] for 24 wks) was superior to adalimumab monotherapy (40 mg SC q2w) in reducing disease activity and improving physical function in RA patients (pts) with an inadequate response or intolerance to methotrexate. <h3>Objectives:</h3> To assess whether pts who achieved clinical response on sarilumab during MONARCH sustained this response in the OLE and to evaluate efficacy and safety of switching from adalimumab to sarilumab vs continuous sarilumab treatment. <h3>Methods:</h3> Pts completing the double-blind phase of MONARCH were eligible for the ongoing OLE, in which all pts receive sarilumab (200 mg SC q2w) for a maximum duration of 276 wks. Disease activity, physical function, and safety were assessed regularly. <h3>Results:</h3> 320/369 Pts enrolled in MONARCH entered the OLE; pts either switched from adalimumab to sarilumab (n=155) or continued on sarilumab (n=165). At OLE entry (Wk 24 of the double-blind phase), the mean &amp;x25B3; from baseline DAS28-ESR was –2.28 in the switch group vs -3.36 in the continuation group, and by Wk 48 was -4.06 vs -4.18, respectively. By Wk 48 of the OLE, the proportion of pts in the switch and continuation groups who achieved DAS28–ESR≤3.2 was 61.3% vs 61.2%, DAS28–ESR&lt;2.6 was 43.9% vs 49.7%, and DAS28-CRP&lt;2.6 was 52.9% vs 52.1%, respectively. From OLE entry to Wk 48, mean HAQ–DI improved in the switch group from 1.21 to 0.91, but did not reach the level of improvements in the continuation group (1.01 to 0.84). See table 1 for ACR responses. After 166 vs 182 cumulative patient-years exposure in the switch vs continuation groups, treatment-emergent adverse events (TEAEs) were observed in 76.1% vs 70.9%, serious TEAEs in 11.0% vs 3.6%, and infections in 41.9% vs 35.8%, respectively, with 2 deaths in the switch group (malignancy; cerebrovascular accident) and 1 death (subarachnoid hemorrhage) in the continuation group. No GI related AEs (ulcerations, perforations or diverticulitis) were observed in either group. <b>Figure 1</b> Mean V from baseline in DAS28-ESR (OLE population; as observed). <h3>Conclusions:</h3> Switching from adalimumab (40 mg q2w) to sarilumab monotherapy (200 mg q2w) improved the signs and symptoms of RA to a similar level as continuous sarilumab treatment, and was associated with a lower HAQ-DI score, which may have resulted in numerical differences in ACR responses between the two groups. <h3>Acknowledgements:</h3> Study funding and medical writing support (Vicki Cronin, Adelphi) provided by Sanofi and Regeneron Pharmaceuticals, Inc. <h3>Disclosure of Interest:</h3> G. R. Burmester Grant/research support from: AbbVie, Pfizer, UCB, Roche, Consultant for: AbbVie, Lilly, Merck Sharpe &amp; Dohme, Pfizer, Sanofi, Roche, UCB, Speakers bureau: AbbVie, Lilly, Merck Sharpe &amp; Dohme, Pfizer, Sanofi, Roche, UCB, G. St John Shareholder of: Regeneron, Employee of: Regeneron, M. Iglesias-Rodriguez Employee of: Sanofi, C.-C. Hu Shareholder of: Sanofi, Consultant for: Astellas, Employee of: Sanofi, Quintiles, T. Raskina: None declared, H. Amital Grant/research support from: Pfizer, Abbvie, Yansen, Consultant for: Pfizer, Merck Sharpe &amp; Dohme, Speakers bureau: Pfizer, Merck Sharpe &amp; Dohme, Yansen, Sanofi, Bristol-Myers Squibb, A. Gomez Centeno Grant/research support from: Boehringer Ingelheim, Celltrion, Galapagos-Gilead, Lilly, Novartis, Pfizer, Roche, Sanofi, UCB, YL Biologics, Consultant for: Abbvie, Biogen, Bristol-Myers Squibb, Celgene, Gebro, Hospira, Lilly, Merck Sharpe &amp; Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi, Speakers bureau: Abbvie, Bristol-Myers Squibb, Gebro, Janssen, Lilly, Menarini, Merck Sharpe &amp; Dohme, Pfizer, Roche, Rubio, UCB, Sanofi, A. Rubbert-Roth Consultant for: Abbvie, Bristol-Myers Squibb, Chugai, Roche, Merck Sharpe &amp; Dohme, Pfizer, Lilly, Hexal/Novartis, Janssen, Sanofi, Speakers bureau: Roche, Chugai, Sanofi, Lilly