CMSC 2012: Natalizumab Interruption Results in a High Rate of MRI and Clinical MS Disease Activity Recurrence

SAN DIEGO — After a 24-week cessation of natalizumab treatment, a high rate of magnetic resonance imaging (MRI) and clinical disease activity recurs in patients with multiple sclerosis (MS), according to research presented at the Fourth Cooperative Meeting of the Consortium of Multiple Sclerosis Centers (CMSC) and America’s Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS).

Natalizumab treatment duration has been associated with the development of progressive multifocal leukoencephalopathy (PML), a rare but often lethal and untreatable disorder of the central nervous system, characterized by large white-matter lesions that occur in immunocompromised patients. The RESTORE study was designed to investigate the effects of natalizumab interruption on MS disease activity.

Robert Fox, MD, of the Mellen Center for Multiple Sclerosis Treatment and Research at the Cleveland Clinic in Ohio, and colleagues conducted the randomized, partially placebo-controlled exploratory RESTORE study. The objective was to evaluate the effects of a 24-week treatment interruption on MS disease activity in 175 patients who had been relapse-free after treatment with natalizumab for a year or more and had no gadolinium-enhancing (Gd+) lesions on baseline MRI scan.

Patients received either natalizumab, placebo or, in an open-label fashion, an alternative immunomodulatory therapy, such as interferon beta-1a (IFNbeta-1a), glatiramer acetate, or methylprednisolone. Rescue treatment with natalizumab or high-dose corticosteroids was allowed if patients experienced a clinical relapse, 1 new Gd+ lesion over 0.8 cubic centimeters in volume, or 2 or more Gd+ lesions.

Overall, 26 percent of patients continued to receive natalizumab, 24 percent received placebo, and 50 percent received an alternative immunotherapy. The majority receiving alternative immunotherapy received methylprednisolone (61 percent), compared with 19 percent each who received IFNbeta-1a or glatiramer acetate. A total of 30 percent of patients, all treated with placebo or alternative immunotherapies, were rescued with natalizumab.

MRI rescue criteria were met for 44 percent of placebo-treated patients, 7 percent of IFNbeta-1a patients, 53 percent of glatiramer patients, and 40 percent of patients rescued with methylprednisolone. No patients who continued to receive natalizumab met MRI rescue critiera. Clinical relapse was observed in 4 percent of natalizumab patients compared with 15 to 29 percent of patients in other arms.

“RESTORE data confirm a high rate of MRI and clinical MS disease activity recurrence after natalizumab cessation. MRI scans helped identify patients with recurring disease activity during natalizumab interruption; the majority of activity was seen at 16-20 weeks,” the authors concluded.

This research was supported by Biogen Idec Inc and Elan Pharmaceuticals, Inc.