Characterization of the Clinical Evidence Supporting Repository Corticotropin Injection for FDA-Approved Indications: A Scoping Review

Importance: Repository corticotropin injection is an expensive medication that was approved in 1952 for the treatment of many inflammatory conditions. The clinical evidence supporting the use of repository corticotropin (hereinafter referred to as corticotropin) has been weak, perhaps because its approval predated the modern review standards of the US Food and Drug Administration (FDA). Objective: To characterize the clinical evidence supporting the use of corticotropin for its FDA-approved indications. Evidence Review: Studies were identified via electronic searches of Ovid MEDLINE, the Cumulative Index of Nursing and Allied Health Literature (CINAHL), and the Cochrane Central Register of Controlled Trials (CENTRAL) from database inception to May 12, 2021 (the MEDLINE search was updated on June 8, 2021). Bibliographies of retrieved articles were also reviewed through ClinicalTrials.gov, FDA documents, and the manufacturer's website. Search terms included HP Acthar, ACTH gel, repository corticotropin, and terms for specific diseases, such as multiple sclerosis, nephrotic syndrome, rheumatoid arthritis, and West syndrome (or spasms, infantile). The review included randomized clinical trials (RCTs), nonrandomized and single-arm clinical trials, and prospective cohort studies that compared corticotropin with an active comparator, placebo, or no treatment. Data were extracted by 1 reviewer and verified by a second. Disagreements were resolved through discussion. Studies were qualitatively synthesized by indication to summarize important design features and results. Findings: Of 1059 records screened, 203 full-text articles were assessed for eligibility. A total of 41 studies involving 2235 participants met inclusion criteria; of those, 11 involved infantile spasms, 10 involved multiple sclerosis (MS), 11 involved rheumatological conditions, 7 involved nephrotic syndrome, 1 involved ocular conditions, and 1 involved sarcoidosis. Overall, 19 studies either included a single arm or exclusively compared different corticotropin dosing strategies. The evidence was most robust for the treatment of infantile spasms and MS. The largest number of studies comparing corticotropin with an active agent (n = 4) or placebo (n = 5) pertained to MS, with almost all studies finding that corticotropin performed better than placebo but no different than corticosteroids. For the treatment of infantile spasms, 8 controlled studies were identified (6 were randomized); of those, only 1 small RCT found corticotropin to be significantly superior to corticosteroids. Studies of patients with other conditions (n = 20) frequently lacked a control group (n = 12), were placebo-controlled (n = 5), or exclusively examined different corticotropin dosing strategies (n = 2). Placebo-controlled RCTs of rheumatoid arthritis, ankylosing spondylitis, optic neuritis, systemic lupus erythematosus, and nephrotic syndrome were generally small and did not consistently demonstrate that corticotropin was superior to placebo. Blinded RCTs showed a similar or greater number of adverse effects with corticotropin relative to corticosteroids. Conclusions and Relevance: In this scoping review, few RCTs supported the clinical benefit of corticotropin for most FDA-approved indications. Most RCTs found that corticotropin was not superior to corticosteroids for treating relapses of MS or infantile spasms.