Megan Brooks

March 12, 2013

A small pilot study suggests a potential benefit of monthly pulse adrenocorticotropic hormone (ACTH) in patients with multiple sclerosis (MS) who experience breakthrough symptoms while receiving standard β-interferon therapy.

Compared with monthly pulse methylprednisolone (MP), monthly pulse ACTH had a more favorable relapse and psychiatric adverse effect profile, Regina Berkovich, MD, PhD, from Keck Medical Center of University of Southern California, Los Angeles, and colleagues found.

The study results were released March 10, ahead of their presentation at the American Academy of Neurology (AAN) 65th Annual Meeting, to be held from March 16 to 23 in San Diego, California.

"ACTH may have immune-modulating mechanisms beyond steroidogenesis that are relevant to the MS disease course," the investigators note in a meeting abstract. "Although ACTH gel is approved to treat MS relapses, its use as pulse therapy is less known."

Fewer Relapses With ACTH

The study team evaluated the efficacy and safety of pulse ACTH treatment added to β-interferon for breakthrough MS, compared with pulse MP, in 23 patients. All the patients were receiving β-interferon and had Expanded Disability Status Scale (EDSS) scores of 3.0 to 6.5 and at least 1 relapse or new T2 or gadolinium-enhanced lesion within the previous year.

Twelve patients were randomly allocated to open-label ACTH (80 U intramuscularly once per day for 3 consecutive days) and 11 to MP (1 g intravenously in 1 dose) monthly for 12 months. Assessments were made every 3 months for 15 months by examiners blinded to treatment allocation.

During that time, patients receiving ACTH had fewer relapses. The cumulative numbers of relapses per patient were 0.08 (95% confidence interval [CI], 0.01 - 0.54) with ACTH and 0.80 (95% CI, 0.36 - 1.75) with MP (risk ratio, 9.56; 95% CI, 1.23 - 74.6; P = .03).

The cumulative number of psychiatric episodes per patient was greater with MP (0.55; 95% CI, 0.12 - 2.6) than with ACTH (0 episodes; P < .0001), as was the cumulative incidence of urinary tract infection (0.65 per patient with MP vs 0.16 per patient with ACTH; P = .25).

In a mixed-effects model, trajectory slopes of EDSS scores over time did not differ between groups, but there was significantly stronger (P = .03) improvement in Mental Health Inventory for ACTH (slope, 0.95 per month; P = .02) compared with MP (slope, 0.29 per month; P = .32).

"Impressive" Results

"These results are of interest because few treatments are available for people with breakthrough MS," Dr. Berkovich commented in a statement from AAN.

To the investigators' knowledge, this is the first study to look at the use of ACTH as a long-term treatment for MS. ACTH is not Food and Drug Administration approved for this use.

Asked for her views on the study, Lily Jung Henson, MD, a neurologist at the Swedish Medical Center, Seattle, Washington, and AAN member, said this is a "very interesting study given the question often raised in the past few years about the value of ACTH. The results are quite impressive but clearly they would have to be reproduced with larger numbers."

Dr. Henson also wonders, "with the number of available therapies currently for relapsing MS, how many people would opt to use yet another injectable drug on top of their baseline injectable instead of switching therapies altogether?"

Further, she notes, "at a time when patients and their neurologists are struggling to get insurers to pay for their DMTs [disease-modifying therapies] because of the significant cost of these drugs, how likely will it be that adjunctive therapy with 2 expensive medications will be approved over switching to 1 costly drug?"

The study was supported by a research grant from Questcor Pharmaceuticals Inc, maker of ACTH. The authors have disclosed no relevant financial relationships. Dr. Henson is an investigator for alemtuzumab (Lemtrada, Sanofi) and has consulted for Genzyme/Sanofi-Aventis and Questcor. 

American Academy of Neurology (AAN) 65th Annual Meeting. Abstract P04.269. March 16-23, 2013.