PMID- 34984839 OWN - NLM STAT- MEDLINE DCOM- 20220428 LR - 20220428 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 28 IP - 3 DP - 2022 Mar TI - 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. PG - 364-371 LID - 10.1111/cns.13789 [doi] AB - INTRODUCTION: About 20%-35% of multiple sclerosis (MS) patients fail to respond to high-dose corticosteroids during a relapse. Repository corticotropin injection (RCI, Acthar((R)) Gel) is a naturally sourced complex mixture of adrenocorticotropic hormone analogs and pituitary peptides that has anti-inflammatory and immunomodulatory effects. AIMS: The study objective was to determine the efficacy and safety of RCI in patients with MS relapse that inadequately responded to corticosteroids. This was a multicenter, double-blind, placebo-controlled study. Nonresponders to high-dose corticosteroids were randomized to receive RCI (80 U) or placebo daily for 14 days. Assessments included improvements on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Clinical Global Impression of Improvement (CGI-I), and adverse events (AEs). RESULTS: Eighteen patients received RCI, and 17 received placebo. A greater proportion of EDSS responders was observed in the RCI group at Day 7, 21, and 42 compared with the placebo group. Qualitative CGI-I showed that more patients receiving RCI were much improved or very much improved than with placebo. No meaningful differences were observed between treatment groups for MSIS-29. No serious AEs or deaths were reported. CONCLUSION: RCI is safe and effective for MS relapse patients who do not respond to high-dose corticosteroids. CI - (c) 2022 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd. FAU - Wynn, Daniel AU - Wynn D AD - Consultants in Neurology, Multiple Sclerosis Center, Northbrook, Illinois, USA. FAU - Goldstick, Lawrence AU - Goldstick L AD - University of Cincinnati Waddell Center for Multiple Sclerosis, Cincinnati, Ohio, USA. FAU - Bauer, William AU - Bauer W AD - Department of Neurosciences, University of Toledo, Toledo, Ohio, USA. FAU - Zhao, Enxu AU - Zhao E AD - Mallinckrodt Pharmaceuticals, Hampton, New Jersey, USA. FAU - Tarau, Eva AU - Tarau E AD - Mallinckrodt Pharmaceuticals, Hampton, New Jersey, USA. FAU - Cohen, Jeffrey A AU - Cohen JA AD - Mellen MS Center, Cleveland Clinic, Cleveland, Ohio, USA. FAU - Robertson, Derrick AU - Robertson D AD - Department of Neurology, University of South Florida, Tampa, Florida, USA. FAU - Miller, Aaron AU - Miller A AD - Icahn School of Medicine at Mount Sinai Hospital, New York, New York, USA. LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20220104 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Adrenal Cortex Hormones) RN - 9002-60-2 (Adrenocorticotropic Hormone) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Adrenocorticotropic Hormone/therapeutic use MH - Chronic Disease MH - Double-Blind Method MH - Humans MH - *Multiple Sclerosis/drug therapy MH - Recurrence PMC - PMC8841301 OTO - NOTNLM OT - Acthar Gel OT - clinical trial OT - multiple sclerosis OT - relapse OT - repository corticotropin injection COIS- Daniel Wynn, MD, has received speaking and/or consulting fees from Acorda Therapeutics, Avanir Pharmaceuticals, Banner Life, Biogen, EMD Serono, Mapi Pharma, Mallinckrodt Pharmaceuticals, Roche/Genentech, Sanofi Genzyme, and Teva. He has received research support from Acorda Therapeutics, Adamas Pharma, Avanir Pharmaceuticals, Bristol Myers Squibb, Chugai Pharma, EMD Serono, Eisai, Jazz Pharmaceuticals, GW Therapeutics, Mallinckrodt Pharmaceuticals, Mapi Pharma, Mylan, Novartis, Osmotica, Receptos/Celgene, SanBio, Sanofi Genzyme, Sunovion, Teva, TG Therapeutics, and the National Multiple Sclerosis Society. Lawrence Goldstick, MD, has received consultancy fees from Biogen, Celgene, EMD Serono, Genentech/Roche, Mallinckrodt Pharmaceuticals, Novartis, Teva Pharmaceuticals, and Sanofi Genzyme. He has received speaker fees from Biogen, Genentech/Roche, Acorda Therapeutics, Mallinckrodt Pharmaceuticals, the National Multiple Sclerosis Society, and Sanofi Genzyme. He has also received research support from Biogen, Alkermes, Acorda Therapeutics, Genentech/Roche, Mallinckrodt Pharmaceuticals, Novartis, Eli Lilly, Sunovion, and Sanofi Genzyme. William Bauer, MD, PhD, has received consultancy fees from Biogen, Mallinckrodt Pharmaceuticals, and Novartis. Enxu Zhao, MS, is an employee of Mallinckrodt Pharmaceuticals. Eva Tarau, MD, is an employee of Mallinckrodt Pharmaceuticals. Jeffrey A. Cohen, MD, has received consultancy fees from Biogen, Bristol Myers Squibb, Convelo, Genentech, Janssen, NervGen, Novartis, and PSI; speaker fees from H3 Communications; and compensation for serving as an editor of Multiple Sclerosis Journal. Derrick Robertson, MD, has received consultancy fees from Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Greenwich Biosciences, Novartis, Sanofi Genzyme, Teva Neuroscience, and Viela Bio. He has received honoraria or speaker fees from Acorda, Alexion, Biogen, Bristol Myers Squibb, EMD Serono, Genentech, Mallinckrodt Pharmaceuticals, Novartis, Sanofi Genzyme, and Teva Neuroscience; and has received research grant support from Biogen, EMD Serono, Genentech, GW Pharmaceuticals, Janssen, Mallinckrodt Pharmaceuticals, MedDay, MedImmune, Novartis, PCORI, Sanofi Genzyme, SunPharma, and TG Therapeutics. Aaron Miller, MD, has received consultancy fees from Accordant, Acorda Therapeutics, Alkermes, Biogen, Celgene, EMD Serono, Genentech/Roche, Mallinckrodt Pharmaceuticals, Mapi Pharma, Novartis, and Sanofi Genzyme; and speaker fees from Biogen and Genentech/Roche. He has also received research support from Biogen, Genentech/Roche, Mallinckrodt Pharmaceuticals, MedDay Pharmaceuticals, Novartis, and Sanofi Genzyme. EDAT- 2022/01/06 06:00 MHDA- 2022/04/29 06:00 PMCR- 2022/01/04 CRDT- 2022/01/05 06:19 PHST- 2021/11/16 00:00 [received] PHST- 2021/12/12 00:00 [accepted] PHST- 2022/01/06 06:00 [pubmed] PHST- 2022/04/29 06:00 [medline] PHST- 2022/01/05 06:19 [entrez] PHST- 2022/01/04 00:00 [pmc-release] AID - CNS13789 [pii] AID - 10.1111/cns.13789 [doi] PST - ppublish SO - CNS Neurosci Ther. 2022 Mar;28(3):364-371. doi: 10.1111/cns.13789. Epub 2022 Jan 4.