Adrenocorticotropic hormone methylprednisolone added to interferon β in patients with multiple sclerosis experiencing breakthrough disease: a randomized, rater-blinded trial

Background: The objective of this study was to evaluate monthly intramuscular adrenocorticotropic hormone (ACTH) gel versus intravenous methylprednisolone (IVMP) add-on therapy to interferon β for breakthrough disease in patients with relapsing forms of multiple sclerosis. Methods: This was a prospective, open-label, examiner-blinded, 15-month pilot study evaluating patients with Expanded Disability Status Scale (EDSS) score 3.0–6.5 and at least one clinical relapse or new T2 or gadolinium-enhanced lesion in the previous year. Twenty-three patients were randomized to ACTH ( n = 12) or IVMP ( n = 11) and completed the study. The primary outcome measure was the cumulative number of relapses. Secondary outcomes included EDSS, Mental Health Inventory (MHI), plasma cytokines, MS Functional Composite (MSFC), Quality-of-Life (MS-QOL) score, bone mineral density (BMD), and new or worsened psychiatric symptoms per month. Brain magnetic resonance imaging was analyzed post hoc . This was a preliminary and small-scale study. Results: Relapse rates differed significantly [ACTH 0.08, 95% confidence interval (CI) 0.01–0.54 versus IVMP 0.80, 95% CI 0.36–1.75; rate ratio, IVMP versus ACTH: 9.56, 95% CI 1.23–74.6; p = 0.03]. ACTH improved ( p = 0.03) MHI (slope 0.95 ± 0.38 points/month; p = 0.02 versus slope −0.38 ± 0.43 points/month; p = 0.39). On-study decreases (all p < 0.05) in eight cytokine levels occurred only in the ACTH group. However, on-study EDSS, MSFC, MS-QOL, BMD, and MRI lesion changes were not significant between groups. Psychiatric symptoms per patient were greater with IVMP than ACTH (0.55, 95% CI 0.12–2.6 versus 0; p < 0.0001). Other common adverse events were insomnia and urinary tract infections (IVMP, seven events each) and fatigue or flu symptoms (ACTH, five events each). Conclusions: This study provided class II evidence that ACTH produced better examiner-assessed cumulative rates of relapses per patient than IVMP in the adjunctive treatment of breakthrough disease in multiple sclerosis