Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Sarilumab is a human mAb blocking the IL-6Rα. In the phase 3 MOBILITY (NCT01061736) and TARGET (NCT01709578) studies, sarilumab (150 or 200 mg subcutaneously every 2 weeks [q2w]) demonstrated efficacy in adults with active, moderate-to-severe RA.1,2 In both studies, infections, neutropenia, injection site reactions, and increased transaminases were among the most common treatment-emergent adverse events. Laboratory changes were consistent with IL-6 signaling blockade. This analysis examined laboratory changes and treatment continuation after sarilumab dose reduction observed through January 2016 in EXTEND (NCT01146652), an open-label, follow-up study evaluating long-term safety and efficacy of sarilumab with or without concomitant conventional synthetic DMARDs.
Methods: Adults with RA who previously participated in sarilumab studies were eligible. Patients who entered into EXTEND initially received sarilumab 150 mg weekly. After dose selection for phase 3 studies, patients were switched to or initiated on sarilumab 200 mg q2w. Per protocol, investigators could reduce the sarilumab dose from 200 mg q2w to 150 mg q2w for absolute neutrophil count (ANC) ≥0.5 to 1.0 Giga/L, platelet count ≥50 to 100 Giga/L, or alanine aminotransferase (ALT) ≥3 to 5 × upper limit of normal. Dose reductions were also performed at the investigator’s discretion. Efficacy data from EXTEND were analyzed before and 24 weeks after dose reduction for MOBILITY (n=148) and TARGET (n=47) patients.
Results: As of the January 2016 interim analysis (N=1652), dose reduction from sarilumab 200 mg q2w to 150 mg q2w had occurred in 17.7% of patients (n=292). The most common reasons for dose reduction were decreased ANC (11.3%; n=187) and increased ALT (3.9%; n=65) levels. The most common non-laboratory reason for dose reduction was infection (0.4%; n=7). At the time of analysis, 76.9% of patients (n=247) whose dose was reduced were continuing treatment, with a median treatment duration of 2.3 years after dose reduction. Improvements in ANC and ALT levels were observed over the 6 months after dose reduction (Table). Sarilumab efficacy was maintained in MOBILITY and TARGET patients 24 weeks after dose reduction as assessed by ACR20 response rates (83.1% and 85.1%, respectively) and improvements in HAQ–Disability Index scores (-0.68 and -0.82, respectively).
Conclusion: In patients whose sarilumab dose was reduced from 200 mg q2w to 150 mg q2w, 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. References: 1. Genovese et al. Arthritis Rheumatol. 2015;67:1424-1437. 2. Fleischmann et al. Presented at: American College of Rheumatology Annual Meeting; November 7-11, 2015; San Francisco, CA.
To cite this abstract in AMA style:Genovese MC, Fay J, Parrino J, Beyer D, Iglesias-Rodriguez M, Graham N, Boddy A, Simon JA, Martincova R, Burmester GR. Sarilumab Dose Reduction in an Open-Label Extension Study in RA Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/sarilumab-dose-reduction-in-an-open-label-extension-study-in-ra-patients/. Accessed December 3, 2020.
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