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

Abstract

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. Twentythree 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 examinerassessed cumulative rates of relapses per patient than IVMP in the adjunctive treatment of breakthrough disease in multiple sclerosis.

Melanocortins, Melanocortin Receptors and Multiple Sclerosis

“…In a small study, dexamethasone was superior to methylprednisolone and ACTH in shortening duration of relapses, but there were only 30 patients in that study [ 115 ]. More recently, a small randomized open label rater blinded study demonstrated that ACTH was more effective than intravenous methylprednisolone for relapses and had greater effects on plasma cytokines, when added to interferon beta [ 116 ]. ACTH as treatment for relapses is generally reserved for patients who are allergic to corticosteroids, develop psychosis with corticosteroid therapy or who fail to respond to treatment with corticosteroids.…”

Recovery of cognitive function after relapse in multiple sclerosis

“…1 The standard treatment is short-course, high-dose corticosteroid therapy, oral versus intravenous methylprednisolone, 2 prednisone or adrenocorticotropic hormone formulated as Acthar Gel injection. 3,4 Largely ignored historically, cognitive dysfunction was recently measured in relapsing MS patients using the Symbol Digit Modalities Test (SDMT). 5,6 In the Safety of TYSABRI Re-dosing and Treatment (STRATA), a year-long, single-arm observational safety study of natalizumab, patients were screened for progressive multifocal leukoencephalopathy (PML) at monthly infusion visits.…”

Methylprednisolone-induced hepatotoxicity in a 16-year-old girl with multiple sclerosis

“…Several treatment options have been proposed in the literature for patients with relapses of MS 43 44. However, even if our patient did not experience further exacerbations, adrenocorticotropic hormone as a first measure and then dexamethasone and plasma exchange seem to be reliable among the most common treatments, according to published data 45–51…”