Subcutaneous Sarilumab in Patients With Rheumatoid Arthritis who Previously Received Subcutaneous Sarilumab or Intravenous Tocilizumab: An Open-Label Extension of a Randomized Clinical Trial

Abstract

Objective: This post hoc analysis evaluated the safety and efficacy of open-label sarilumab in patients with rheumatoid arthritis (RA) who completed the phase III double-blind ASCERTAIN study (NCT01768572) and switched from intravenous (IV) tocilizumab to subcutaneous (SC) sarilumab, or who continued SC sarilumab in the open-label extension (OLE) study EXTEND (NCT01146652).

Methods: Patients who completed ASCERTAIN were eligible to enroll in EXTEND to receive sarilumab 200 mg SC every 2 weeks (Q2W). Safety and efficacy were reported through 96 weeks in the OLE in patients who switched from tocilizumab IV to sarilumab 200 mg SC Q2W, who switched from sarilumab 150 mg SC Q2W to sarilumab 200 mg SC Q2W, or who continued sarilumab 200 mg SC Q2W.

Results: Of 175 patients who completed ASCERTAIN, 168 (96%) enrolled in EXTEND, and 38 of these patients (23%) discontinued the OLE. Cumulative sarilumab exposure during follow-up was 273.7 patient-years. No new safety signals were identified, infections occurred at a rate of 59.9/100 patient-years, and there were no cases of grade 4 neutropenia. Efficacy-as assessed by Disease Activity Score (28 joints) based on C-reactive protein, Clinical Disease Activity Index, and Health Assessment Questionnaire-Disability Index scores-was sustained over 96 weeks of follow-up when switching to, or continuing, sarilumab 200 mg SC Q2W.

Conclusion: Switching from IV to SC interleukin-6 receptor inhibitor therapy produced no new safety concerns, and clinical efficacy was sustained over 96 weeks of follow-up. These findings alleviate potential concerns over switching route of administration with interleukin-6 receptor inhibitor therapy for RA.

© 2020 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

Figures

Figure 1

Patient disposition through the OLE. Abbreviations: IV, intravenous; OLE, open‐label extension; Q2W, every 2 weeks; Q4W, every 4 weeks; RCT, double‐blind randomized control phase; SC, subcutaneous. aPatients requesting discontinuation is not additive with the number of patients who discontinued.

Figure 2

Mean (±SE) efficacy scores from OLE baseline to week 96 in overall patient population (observed cases) for DAS28‐CRP (A, B), CDAI (C, D), and HAQ‐DI (E, F). Abbreviations: CDAI, Clinical Disease Activity Index; DAS28‐CRP, Disease Activity Score (28 joints) based on C‐reactive protein; HAQ‐DI, Health Assessment Questionnaire‐Disability Index; IV, intravenous; OLE, open‐label extension; Q2W, every 2 weeks; Q4W, every 4 weeks; SC, subcutaneous.

Figure 3

Percentage of patients (OC and ITT) who achieved disease activity thresholds at OLE baseline and sustained them following switch to open‐label sarilumab at OLE weeks 12 and 96. Abbreviations: CDAI, Clinical Disease Activity Index; DAS28‐CRP, Disease Activity Score (28 joints) based on C‐reactive protein; ITT, intention‐to‐treat patient population; IV, intravenous; OC, observed case patient population; OLE, open‐label extension; Q2W, every 2 weeks; Q4W, every 4 weeks; SC, subcutaneous. aUses the number of patients assessed at each time point as the denominator for the percentage of patients achieving disease activity thresholds at each time point. bUses the number of patients achieving disease activity thresholds at OLE baseline as the denominator for the percentage of patients achieving disease activity thresholds at each time point.