Background Sarilumab is a human mAb blocking the IL-6Rα. In the phase 3 TARGET study (NCT01709578), sarilumab (150 or 200 mg SC q2w) + csDMARDs demonstrated efficacy in adults with active, moderate-to-severe RA and inadequate response or intolerance to ≥1 TNFi. Infections, neutropenia, injection site reactions, increased lipids, and increased transaminases were among the most common TEAEs. EXTEND (NCT01146652) is an open-label extension study evaluating long-term safety and efficacy of sarilumab in patients from the sarilumab clinical development program.
Objectives To examine the effects of dose reduction of sarilumab 200 mg q2w to 150 mg q2w in patients from TARGET that occurred in EXTEND primarily for protocol-specified laboratory abnormalities.
Methods Patients were switched to or initiated on sarilumab 200 mg q2w after enrolling in EXTEND. Per protocol, investigators could reduce the sarilumab dose from 200 mg q2w to 150 mg q2w for ANC ≥0.5 to 1.0 Giga/L, platelet count ≥50 to 100 Giga/L, or ALT ≥3 to 5 × ULN. Dose reductions were also performed at the investigator's discretion. Efficacy data from EXTEND were analyzed before and 24 weeks after dose reduction.
Results As of the July 2016 interim analysis (N=452), dose reduction from sarilumab 200 mg q2w to 150 mg q2w had occurred in 14.6% of patients (n=66) from TARGET. The most common reasons for dose reduction were decreased ANC (8.8%; n=40) and increased ALT (3.3%; n=15). At the time of analysis, 80.3% of patients (n=53) whose dose was reduced were continuing treatment, with a median treatment duration of 1.6 years after dose reduction. Improvements in ANC and ALT were observed over the 6 months after dose reduction (Table 1). Efficacy was maintained 24 weeks after dose reduction (Table 2).
Conclusions In patients from TARGET whose sarilumab dose was reduced from 200 mg q2w to 150 mg q2w during EXTEND, there was an improvement in laboratory abnormalities and continuation of treatment for the majority of patients. Improvements in signs and symptoms of RA and physical function were maintained after dose reduction.
Acknowledgements This study was sponsored by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc. Editorial support was provided by MedThink SciCom and funded by Sanofi Genzyme and Regeneron Pharmaceuticals, Inc.
Disclosure of Interest R. Fleischmann Grant/research support from: AbbVie, Amgen, Ardea Biosciences, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Eli Lilly, Pfizer, Roche, Sanofi, and UCB, Consultant for: AbbVie, Akros Pharma, Amgen, AstraZeneca, Bristol-Myers Squibb, Janssen, Eli Lilly, Pfizer, Roche, and UCB, P. Hrycaj Consultant for: Pfizer, Celltrion, and Egis, H. van Hoogstraten Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, E. Mangan Shareholder of: Regeneron Pharmaceuticals, Inc, Employee of: Regeneron Pharmaceuticals, Inc, Y. Lin Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, S. Jayawardena Shareholder of: Sanofi Genzyme, Employee of: Sanofi Genzyme, G. Burmester Grant/research support from: AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Consultant for: AbbVie, Bristol-Myers Squibb, MedImmune, Merck, Pfizer, Roche, and UCB, Speakers bureau: AbbVie, Bristol-Myers Squibb, Merck, Pfizer, Roche, and UCB