Five-day regimen of intramuscular or subcutaneous self-administered adrenocorticotropic hormone gel for acute exacerbations of multiple sclerosis: a prospective, randomized, open-label pilot trial

Abstract

Background: Despite over 50 years of experience with adrenocorticotropic hormone (ACTH) as a treatment for acute exacerbations of multiple sclerosis, there have been no trials examining the options of the 2-3-week dosing regimen or intramuscular injection protocol used in the original trials. At our clinic, we performed a small, prospective, randomized pilot study to examine the efficacy and safety of, and patient satisfaction with, a short (five-day) self-administered ACTH dosing protocol for exacerbations of multiple sclerosis, and to compare the subcutaneous and intramuscular routes of administration.

Methods: Patients for this study were recruited from an outpatient treatment clinic. Each patient self-administered natural ACTH gel 80 U/day by subcutaneous or intramuscular injection for five consecutive days and was evaluated at baseline and on days 7 and 14. Patient feedback was collected using the Patient Global Impression of Change (PGI-C, the primary efficacy measure), a patient global visual analog scale, the Expanded Disability Status Scale, a timed walk, the Nine-hole Peg Test, and the Clinical Global Impression of Change.

Results: Of the 20 enrolled patients (mean age 39.5 years), 19 completed the study. On day 14, 61.1% of patients (11 of 18 with day 14 scores) were treatment responders, and rated their condition as "very much improved" or "much improved" on the PGI-C. The intramuscular group had numerically more responders, but there was no significant difference in the proportion of responders between the intramuscular and subcutaneous groups at day 14 (P = 0.3). The intramuscular route of injection was associated with more injection site pain than the subcutaneous route.

Conclusion: A shorter five-day course of intramuscular or subcutaneous ACTH gel may improve symptoms associated with acute exacerbations of multiple sclerosis. Larger studies with standard of care controls are needed to confirm whether this shorter course of intramuscular or subcutaneous ACTH gel is effective and could potentially be substituted for the standard 14-day treatment.

Keywords: ACTH; Acthar® Gel; acute exacerbations; adrenocorticotropic hormone; autoimmune diseases; multiple sclerosis.

Figure 1

Study design. Study subjects were randomized to self-administer either 80 U of intramuscular ACTH gel or 80 U of subcutaneous ACTH gel daily on days 1–5 of the study. Abbreviations: IM, intramuscular; SC, subcutaneous; ACTH, adrenocorticotropic hormone.

Figure 2

Percentage of responders as determined by the Patient Global Impression of Change (A) and Clinical Global Impression of Change (B) score cards on days 7 and 14. Responders were defined by a patient or clinical response of “much improved” or “very much improved.” Both assessments reported a drug response to a five-day treatment in both the IM and SC groups, and an increase in drug response at day 14. Abbreviations: CGI, clinical global impression of change; IM, intramuscular; SC, subcutaneous.

Figure 3

Mean improvement on the visual analog scale in the IM (A) and SC (B) groups. Comparable improvement of the symptoms of acute exacerbation was noted in both IM and SC groups on the patient visual analog scale. Abbreviations: LOCF, last observation carried forward; SC, subcutaneous; IM, intramuscular.