Repository corticotropin injection in patients with persistently active SLE requiring corticosteroids: post hoc analysis of results from a two-part, 52-week pilot study.

Richard A Furie,Patrice M Becker,Margaret Mitrane,Enxu Zhao

doi:10.1136/lupus-2017-000240

Abstract

ObjectivePost hoc analyses evaluated the effectiveness and safety of repository corticotropin injection (RCI) in patients with persistently active SLE over 52 weeks.MethodsPatients were initially randomised to 40 U daily or 80 U every other day RCI (n=26) or placebo (n=12) for the 8-week double-blind period. Completers entered the open-label extension (OLE; n=33) receiving 16, 40 or 80 U RCI 1–3 times/week and were followed through week 52. Outcomes included proportion of responders based on a novel index (resolution of joint or skin activity using hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) without any worsening British Isles Lupus Assessment Group (BILAG) scores in other organ systems) or revised novel index (using SLE Responder Index (SRI) definition of BILAG worsening (1A or 2B)), proportion of responders by SRI and changes in total hSLEDAI and BILAG scores. Adverse events and laboratory values were assessed.ResultsAt week 52, 12.0% (3/25) RCI/RCI patients and 36.4% (4/11) placebo/RCI patients were responders using the novel index. The revised novel responder index demonstrated response rates of 48.0% (12/25) and 54.5% (6/11) in the RCI/RCI and placebo/RCI groups, respectively. Proportions of SRI responders were 40.0% (10/25) and 54.5% (6/11). In the RCI/RCI group, total hSLEDAI and BILAG scores declined from 10.0 and 15.7 at week 0 to 3.5 and 4.6 at week 52, respectively. Reductions in the placebo/RCI group on switching were observed (mean hSLEDAI: 9.1–3.3; BILAG: 13.5–2.6). Other disease activity endpoints also improved in both groups. No new safety signals were observed during the OLE.ConclusionsRCI demonstrated durable effectiveness in patients with persistently active SLE despite moderate-dose corticosteroid therapy. Switching from placebo resulted in reduced disease activity during the OLE. These data provide the foundation for evaluation of RCI in a robustly powered study.

Highlights

SLE is a systemic autoimmune disease that results in significant and irreversible damage to multiple organs.[1]
►► This post hoc analysis of results from a two-part pilot study consisting of an 8-week, prospective, randomised, double-blind, placebo-controlled phase, followed by a 44-week open-label extension (OLE), demonstrated sustained improvements in signs and symptoms of SLE in patients treated with repository corticotropin injection
All measures of disease activity were higher for the placebo/repository corticotropin injection (RCI) group versus the RCI/RCI group at the OLE baseline

Summary

Introduction

SLE is a systemic autoimmune disease that results in significant and irreversible damage to multiple organs.[1]. ►► This post hoc analysis of results from a two-part pilot study consisting of an 8-week, prospective, randomised, double-blind, placebo-controlled phase, followed by a 44-week open-label extension (OLE), demonstrated sustained improvements in signs and symptoms of SLE in patients treated with repository corticotropin injection (RCI; H.P. Acthar Gel) for a total of 52 weeks. Inflammation and organ damage are exacerbated by infiltration of leucocytes and the release of proinflammatory chemokines and cytokines.[1,2,3] The aetiology of lupus is multifactorial, but B lymphocyte hyperactivity and loss of tolerance are major drivers of the disease.[1] Affecting about 14–68 in every 100 000 persons in the USA,[2] with similar prevalences in other parts of the world,[4 5] SLE is associated with significant morbidity and mortality.[6]. There are important unmet treatment needs in SLE: conventional immunosuppressive agents have significant

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Conclusion