Preventing New Enhancing Lesions and Relapses After Discontinuing Tysabri

Background: Patients with multiple sclerosis (MS) receiving natalizumab (Tysabri^®) infusions may discontinue treatment due to a positive JC virus (JCV) antibody status alone or positive status and length of time on infusions, as these factors increase the risk of developing progressive multifocal leukoencephalopathy (PML). Patients may experience a clinical relapse and/or develop new enhancing lesions following discontinuation of natalizumab, even in the absence of PML. For example, a patient in our practice experienced a clinical relapse with vertigo, optic neuritis, and weakness associated with 5 new enhancing brain lesions and 1 enhancing thoracic cord lesion. Therefore, we aimed to establish a treatment algorithm to reduce the risk of developing a relapse or new enhancing lesions after discontinuing natalizumab. Adrenocorticotropic hormone (ACTH) gel (H.P. Acthar^® Gel, repository corticotropin injection) is FDA-approved for treatment of acute MS exacerbations in adults.

Objectives: The goal of our pilot case series was to use ACTH to reduce inflammation after discontinuing natalizumab and before symptoms or new enhancing MS lesions occurred (an off-label use).

Methods: Patients who discontinued natalizumab due to JCV antibody positive status (alone or in combination with length of time on infusion) were treated with ACTH gel 80 units SQ QD x 5 days at Week 4, Month 2, and Month 3 after discontinuing natalizumab. Disease-modifying therapy (DMT) was initiated at Week 4 with glatiramer acetate (Copaxone®) or Week 6 with intravenous immunoglobulin (IVIG). Data collected included information from patient records, MRIs, and neurological exam.

Results: We report results for 5 patients (4 female, 1 male; aged 35-57 years) who have been treated with the ACTH protocol following discontinuation of natalizumab treatment (duration of 8-31 months); 4 patients also received glatiramer acetate and 1 received IVIG. At varying intervals for MRI surveillance (2 patients at 4 months; 1 patient each at 6, 7, and 12 months), patients did not develop symptoms of a clinical MS relapse or develop new enhancing lesions on MRI using a 3 Tesla magnet with gadolinium.

Conclusions: Patients who were treated using a protocol of monthly pulse ACTH and a DMT following discontinuation of natalizumab showed no increase in new enhancing T2 lesions on MRI and no new clinical relapse symptoms during up to 12 months of follow up.