Objective Evaluate open-label sarilumab monotherapy in patients with rheumatoid arthritis switching from adalimumab monotherapy in MONARCH (NCT02332590); assess long-term safety and efficacy in patients continuing sarilumab during open-label extension (OLE).
Methods During the 48-week OLE, patients received sarilumab 200 mg subcutaneously once every 2 weeks. Safety (March 2017 cut-off) and efficacy, including patient-reported outcomes, were evaluated.
Results In the double-blind phase, patients receiving sarilumab or adalimumab monotherapy showed meaningful improvements in disease activity; sarilumab was superior to adalimumab for improving signs, symptoms and physical function. Overall, 320/369 patients completing the 24-week double-blind phase entered OLE (155 switched from adalimumab; 165 continued sarilumab). Sarilumab safety profile was consistent with previous reports. Treatment-emergent adverse events were similar between groups; no unexpected safety signals emerged in the first 10 weeks postswitch. Among switch patients, improvement in disease activity was evident at OLE week 12: 47.1%/34.8% had changes ≥1.2 in Disease Activity Score (28 joints) (DAS28)-erythrocyte sedimentation rate/DAS28-C-reactive protein. In switch patients achieving low disease activity (LDA: Clinical Disease Activity Index (CDAI) ≤10; Simplified Disease Activity Index (SDAI) ≤11) by OLE week 24, 70.7%/69.5% sustained CDAI/SDAI LDA at both OLE weeks 36 and 48. Proportions of switch patients achieving CDAI ≤2.8 and SDAI ≤3.3 by OLE week 24 increased through OLE week 48. Improvements postswitch approached continuation-group values, including scores ≥normative values.
Conclusions During this OLE, there were no unexpected safety issues in patients switching from adalimumab to sarilumab monotherapy, and disease activity improved in many patients. Patients continuing sarilumab reported safety consistent with prolonged use and had sustained benefit.
- DMARDs (biologic)
- rheumatoid arthritis
- disease activity
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Contributors GRB contributed to the design of the study. GRB, HA, TR, AG-C and AR-R contributed to data acquisition. KT contributed to data review and addressed data-related queries. All authors contributed to data analysis and interpretation; were involved in revising the manuscript critically for important intellectual content and approved the final version to be published.
Funding This study was supported by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc., which funded medical writing support by Vicki Cronin, PhD, Adelphi Communications, Ltd.
Competing interests GRB has received research grants or consulting fees or participated in speakers’ bureaus from/for AbbVie, Eli Lilly, Merck Sharp & Dohme, Pfizer, Roche, Sanofi and UCB. VS has received consulting fees from AbbVie, Amgen, AstraZeneca, Biogen, Bristol-Myers Squibb, Celltrion, CORRONA, Crescendo, Eli Lilly, Genentech/Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Sandoz, Sanofi and UCB. AR-R has attended speakers’ bureaus for AbbVie, Bristol-Myers Squibb, Chugai, Eli Lilly, Hexal/Novartis, Janssen, Merck Sharp & Dohme, Pfizer, Roche and Sanofi and has provided consultancy for Chugai, Eli Lilly, Roche and Sanofi. HA has received grant/research support from AbbVie, Janssen and Pfizer, has attended speakers’ bureaus for Bristol-Myers Squibb, Janssen, Merck Sharp & Dohme, Pfizer and Sanofi and has provided consultancy for Merck Sharp & Dohme and Pfizer. TR has nothing to declare. AG-C has received research grants from Boehringer Ingelheim, Celltrion, Eli Lilly, Galapagos-Gilead, Novartis, Pfizer, Roche, Sanofi, UCB and YL Biologics and consulting/speakers’ fees or other remuneration from AbbVie, Biogen, Bristol-Myers Squibb, Celgene, Eli Lilly, Gebro, Hospira, Janssen, Menarini, Merck Sharp & Dohme, Pfizer, Roche, Rubio, Sandoz, Sanofi and UCB. CP-R was formerly an employee of Sanofi, and may hold stock and/or stock options in the company. LG is an employee of Sanofi Genzyme, and may hold stock and/or stock options in the company. KT is a former employee of Sanofi Genzyme, may hold stock and/or stock options in the company, and is currently employed by EMD Serono. GSJ and SB are employees of Regeneron Pharmaceuticals, Inc., and may hold stock and/or stock options in the company. MCG has received research grants and/or consulting fees from GlaxoSmithKline, R-Pharm, Roche, and Sanofi.
Patient consent for publication Not required.
Ethics approval The MONARCH and MONARCH OLE protocols were approved by appropriate ethics committees/institutional review boards; Ethik-Kommission des Landes Berlin Landesamt für Gesundheit und Soziales in Berlin (approval number: 14/0562-EK 11) and from each of the 85 additional study centres in Europe (including Israel and Russia), South Africa, South America, South Korea and the USA.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Qualified researchers may request access to patient-level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan and dataset specifications. Patient-level data will be anonymised and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi’s data sharing criteria, eligible studies and process for requesting access can be found at: https://www.clinicalstudydatarequest.com.
Author note CP-R was working at Sanofi Genzyme, Bridgewater, NJ, USA, for the study duration, data analyses, and the majority of the manuscript development, and has since left the company. CP-R's current address is 17, Route des Crans, Celigny 1298, Switzerland. KT was working at Sanofi Genzyme, Cambridge, MA, USA, for the study duration, data analyses, and the majority of the manuscript development, and has since left the company. KT is currently employed by EMD Serono.
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