Acthar Gel May Help RRMS Patients Who Fail Corticosteroids
Acthar Gel (repository corticotropin injection) may be useful for managing disease relapses in people with relapsing-remitting multiple sclerosis (RRMS) who fail to respond to treatment with corticosteroids, according to results from a small clinical trial.
The study, “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,” was published in CNS Neuroscience & Therapeutics. It was funded by Mallinckrodt Pharmaceuticals, which sells Acthar Gel.
RRMS, the most common type of MS, is characterized by relapses — periods when symptoms worsen suddenly. Relapses typically are followed by remissions, when symptoms ease, although some symptoms may linger and lead to worsening disability even in remission.
The standard treatment for RRMS relapses is corticosteroids, which work by mimicking the activity of a naturally occurring anti-inflammatory molecule called cortisol. However, up to a third of RRMS patients don’t respond to corticosteroid treatment.
Acthar Gel contains a naturally derived combination of pituitary signaling molecules that work to increase the body’s cortisol levels, among other anti-inflammatory effects. Here, researchers at Mallinckrodt and other institutions in the U.S. conducted a clinical trial to evaluate whether this medication may be useful for treating relapses in RRMS patients who did not respond to corticosteroids.
The Mallinckrodt-sponsored Phase 4 trial called OPTIONS (NCT03126760) enrolled 35 people with RRMS. All the patients had experienced a relapse and been treated with corticosteroids within a month of starting the trial, but did not respond to the treatment.
The patients were divided randomly to receive either Acthar Gel (80 units) or placebo, injected under the skin once daily for 14 days. In both groups, the average age was about 41 years, and most participants were female and white. Participants were followed for up to 42 days after dosing.
The study’s main goal was to assess the proportion of “responders” to treatment based on changes in the Expanded Disability Status Scale. Specifically, “responders” were defined as an improvement of at least one point if the starting EDSS score had been 5.5 or lower, or a 0.5-point improvement in those with a starting EDSS score above 5.5.
Of note, the EDSS score moves in 0.5-point increments, with higher numbers reflecting more substantial disability. A score of 5.5 is defined as the point at which disability is severe enough that a person can no longer do normal daily activities.
The percentage of responders at day 42 was significantly higher in the Acthar Gel group compared with the placebo group (61.1% vs. 11.8%). Significant differences also were seen at days seven and 21.
“RCI-treated patients showed substantial improvements on the EDSS … compared with placebo,” the researchers wrote.
Based on the Clinical Global Impression of Improvement Scale (CGI-I) — a clinician-based assessment of overall patient health — slightly more patients given Acthar Gel than placebo were either “much improved” (50% vs. 41.2%) or “very much improved” (38.9% vs. 29.4%).
Patient-reported quality of life “did not show meaningful differences” between the two groups, the researchers reported. Scores on the Multiple Sclerosis Impact Scale (MSIS-29), which measures the disease’s impact in day-to-day life, also were not different between the groups.
“Both [Acthar Gel] and placebo groups showed improvements in the MSIS-29 and CGI-I scores compared to baseline [the start of the trial], but there were no substantial differences between treatment groups,” the researchers wrote.
The rate of adverse events (side effects) deemed possibly or probably related to treatment was 61.1% in the Acthar Gel group and 47.1% in the placebo group. In both groups, the most common adverse event was bruising at the injection site.
One participant in the Acthar Gel group withdrew from the study due to swelling and pain, which resolved about three weeks after stopping the medication. No serious adverse events were reported.
Overall, Acthar Gel “was shown to be well tolerated overall in this subset of RRMS patients,” the researchers wrote.
“These results support that [Acthar Gel] is safe and effective for the treatment of patients with MS relapse that did not adequately respond to corticosteroids,” the team concluded.
A noted limitation of this study was the small number of participants. The study originally sought to recruit nearly twice as many patients, but was terminated early due to the COVID-19 pandemic.