Results from a Multicenter, Randomized, Double Blind, Placebo-Controlled Study of Repository Corticotropin Injection for Relapsing-Remitting Multiple Sclerosis

Background: Patients with relapsing-remitting multiple sclerosis (RRMS) may experience acute relapses that are nonresponsive (20-35%) to high-dose corticosteroids. Repository corticotropin injection (RCI; Acthar® Gel) is approved by the US FDA for the treatment of MS relapses. RCI is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and other pituitary peptides that has anti-inflammatory and immunomodulatory effects by engaging melanocortin receptors.

Objectives: The multicenter, randomized, double-blind, placebo-controlled, parallel-group OPTIONS trial assessed the efficacy and safety of RCI in patients with RRMS experiencing an acute relapse and inadequate response to high-dose corticosteroids (NCT03126760).

Methods: Patients experiencing a relapse received 3 to 5 days of intravenous or oral methylprednisolone (1 g/d) or oral prednisone (1250 mg/d) within 28 days of relapse onset. Patients without a ≥1-point improvement in ≥1 function of the Functional Systems Score (FSS) at 14 days after steroid initiation were randomized (1:1) to subcutaneous RCI 1 mL (80 U) or matching placebo (PBO) daily for 14 days. Responses were evaluated up to 42 days after randomization using the Expanded Disability Status Scale (EDSS), Clinical Global Impression of Improvement (CGI-I) scale, 29-item MS Impact Scale (MSIS-29), and adverse events (AEs). The primary efficacy endpoint was EDSS response rate at day 42, defined as the percentage of patients with an EDSS score improvement of ≥1.0 point (if ≤5.5 at baseline) or ≥0.5 point (if >5.5 at baseline).

Results: Thirty-five patients completed the study: 77.1% women and 85.7% White. A greater proportion (with 90% confidence intervals) of EDSS responders were observed in the RCI group on days 42 (primary endpoint; RCI, 61.1% [42.0, 77.3]; PBO, 11.1% [4.0, 30.1]); 21 (RCI, 38.9% [22.7, 58.0]; PBO, 23.5% [11.0, 43.3]), and 7 (RCI, 38.9% [22.7, 58.0]; PBO, 11.8% [4.0, 30.1]). Qualitative CGI-I analyses showed that 88.9% of patients receiving RCI vs 70.6% receiving placebo were very much or much improved by day 42. No significant treatment differences were observed for MSIS-29. Incidence of treatment-emergent AEs was similar between RCI (77.8%) and placebo (70.6%) groups, with no serious AEs or deaths in the RCI group.

Conclusions: These results support RCI as a safe and highly effective treatment for MS relapse in patients with an inadequate response to high-dose corticosteroids.