A Prospective Observational Registry of Repository Corticotropin Injection (Acthar® Gel) for the Treatment of Multiple Sclerosis Relapse

Abstract

Background and Purpose: Effective relapse treatment is critical for minimizing disability in patients with multiple sclerosis (MS). Repository corticotropin injection (RCI; Acthar® Gel) has demonstrated efficacy for the treatment of MS exacerbations. However, there is limited real-world evidence available regarding the relationship between the use of RCI for MS relapses and patient demographics, disease characteristics, and dosing regimens. In this multicenter, prospective, observational registry, patients receiving RCI for acute MS relapse were characterized, and recovery and safety outcomes were described.Methods: Patients were invited by their treating clinician to participate in the registry during a routine care visit. The decision to initiate RCI occurred before determination of study eligibility. All treatment decisions were made at the discretion of the patient's health care provider and were not mandated by the study design or protocol. Each enrolled patient was followed for up to 24 Months or until the date of study termination. The primary endpoint was the change from baseline in MS Impact Scale Version 1 (MSIS-29v1) physical subscale scores at Month 2. Additional assessments included the MSIS-29v1 psychological subscale, Expanded Disability Status Scale (EDSS), Clinical Global Impression of Improvement (CGI-I), Work Productivity and Activity Impairment Questionnaire: MS (WPAI:MS), and Health Resource Utilization (HRU) questionnaire.Results: Of 145 patients enrolled, 82 (56.6%) completed 24 Months of follow-up. Mean MSIS-29v1 physical subscale scores improved at 2 Months (−8.0; P = 0.0002) and 6 Months (−9.6; P < 0.0001). Mean MSIS-29v1 psychological subscale scores also improved at 2 Months (−7.9; P = 0.0040) and 6 Months (−9.9; P = 0.0012). Mean EDSS scores improved at 2 Months (−0.4; P < 0.0001) and 6 Months (−0.5; P < 0.0001). CGI-I scores indicated improvement in 63.4% of 71 patients at 2 Months and 61.4% of 57 patients at 6 Months (both P < 0.0001). Improvements on the WPAI:MS activity impairment domain (P < 0.001) and reductions in outpatient, specialist, and emergency department visits were observed at 2 and 6 Months. A total of 35 (28.0%) patients reported 83 adverse events; 11 (8.8%) patients reported 16 serious adverse events.Conclusions: This observational study found significant improvements in MS assessment scores after RCI treatment and supports the efficacy and tolerability of RCI for MS relapse.Clinical Trial Registration: This trial is registered on ClinicalTrials.gov with the identifier NCT02633033.

Cost-Effectiveness of Repository Corticotropin Injection for the Treatment of Acute Exacerbations in Multiple Sclerosis

“…30 Baseline patient distribution by EDSS state and relapse severity were derived from the MS Relapse Registry, titled "Observational Registry of Acthar Gel for Participants with Multiple Sclerosis Relapse," funded by Mallinckrodt Pharmaceuticals (N = 125; Table 1). 17,31 The study was conducted to monitor the course of MS and to document relapses and the recovery process, in a group of MS patients treated with RCI.…”

“…7,16 Further, clinically meaningful improvements in MS Impact Scale 29 item version 1 (MSIS-29v1) physical subscale were observed in a prospective observational study of patients with treatment-refractory MS on RCI. 17 Statistically significant improvements in clinician-rated scales (Expanded Disability Status Scale [EDSS] and Clinical Global Impression of Improvement [CGI-I]) were also observed. 17 A retrospective claims analysis comparing RCI and alternative therapies supported the effectiveness of RCI in reducing relapses in MS. 8,18 Further, a recent literature review corroborates the efficacy of RCI in MS. 16 Initial economic analyses indicated that RCI was costsaving compared to PMP or IVIg in resolving MS relapses from a payer perspective.…”

“…17 Statistically significant improvements in clinician-rated scales (Expanded Disability Status Scale [EDSS] and Clinical Global Impression of Improvement [CGI-I]) were also observed. 17 A retrospective claims analysis comparing RCI and alternative therapies supported the effectiveness of RCI in reducing relapses in MS. 8,18 Further, a recent literature review corroborates the efficacy of RCI in MS. 16 Initial economic analyses indicated that RCI was costsaving compared to PMP or IVIg in resolving MS relapses from a payer perspective. 19,20 Considering the societal burden of MS relapses, 21 it is important to evaluate these treatments considering this perspective to optimize patient care.…”

Results from a multicenter, randomized, double‐blind, placebo‐controlled study of repository corticotropin injection for multiple sclerosis relapse that did not adequately respond to corticosteroids

“…Repository corticotropin injection (RCI; Acthar ® Gel, Mallinckrodt Pharmaceuticals, Hampton, NJ, USA) is a naturally sourced complex mixture of adrenocorticotropic hormone (ACTH) analogs and other pituitary peptides. 7 RCI is currently approved by the US Food and Drug Administration (FDA) for treatment of exacerbations of MS. 7 RCI is anti‐inflammatory by stimulating endogenous corticosteroid production and can exert additional immunomodulatory effects by binding to melanocortin receptors (MCRs) on immune cells. 8 , 9 , 10 Notably, in vitro studies have shown that RCI elicits distinct functional activity at MCRs from that of synthetic MCR agonists.…”

Repository Corticotropin Injection (Acthar® Gel) for Refractory Severe Noninfectious Keratitis: Efficacy and Safety from a Phase 4, Multicenter, Open-Label Study

“…RCI is approved by the US Food and Drug Administration for the treatment of severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, including keratitis [7]. RCI has also been found effective for the treatment of persistently active systemic inflammatory disorders that have not responded to corticosteroids and other standard-of-care therapies [18][19][20][21].…”