Patients with multiple sclerosis (MS) who are undergoing treatment with disease-modifying agents such as natalizumab are at risk of developing progressive multifocal leukoencephalopathy (PML) and rebound disease activity following discontinuation. The efficacy of dimethyl fumarate as an exit strategy after natalizumab withdrawal was investigated in a longitudinal study published in the Journal of Neurology, Neurosurgery, and Psychiatry.
A total of 39 patients with relapsing-remitting MS who were at high risk for PML were switched from natalizumab to dimethyl fumarate. Clinical and magnetic resonance imaging (MRI) data on all participants were collected for the 2-year period preceding natalizumab treatment (pre-natalizumab phase), the 2 years of natalizumab therapy (natalizumab phase), and the 2 years of dimethyl fumarate treatment (dimethyl fumarate phase).
During the pre-natalizumab phase, all patients experienced ≥1 relapse. In contrast, during the natalizumab phase, 3 of 39 patients (7.7%) experienced ≥1 relapse (all occurred during the first 6 months of natalizumab therapy). During the dimethyl fumarate phase, 5 of 39 patients (12.8%) experienced ≥1 relapse.
In the pre-natalizumab phase, increased disability progression was reported in 23 of 39 patients (58.9%). In contrast, in the natalizumab phase, only 1 of 39 patients (2.6%) experienced increased disability. In the dimethyl fumarate phase, 3 of 39 patients (7.7%) had disability progression. The increase in disability was significantly higher during the pre-natalizumab phase than the natalizumab and dimethyl fumarate phases (P <.001), but not between the natalizumab and dimethyl fumarate phases (P =.180)
During the pre-natalizumab phase, all patients had evidence of new or enlarged lesions on MRI. During the natalizumab phase, 6 of 39 patients (15.4%) had MRI activity; during the dimethyl fumarate phase, 8 of 39 patients (20.5%) had MRI activity. A significant difference in MRI activity was observed between pre-natalizumab and natalizumab treatment (P <.001), but not between natalizumab and dimethyl fumarate treatment (P =.282).
Two dropouts were reported, one due to disease rebound activity and 1 due to gastrointestinal side effects. Overall, nearly 80% of the patients continued to have no evidence of disease activity at the end of dimethyl fumarate therapy.
Dimethyl fumarate may represent an appropriate exit strategy following natalizumab withdrawal, particularly in those individuals exhibiting low to moderate disease activity in the pre-natalizumab and natalizumab phases. Patients with very high disease activity should be encouraged to switch to other agents.
Calabrese M, Pitteri M, Farina G, et al. Dimethyl fumarate: a possible exit strategy from natalizumab treatment in patients with multiple sclerosis at risk for severe adverse events [published online August 27, 2017]. J Neurol Neurosurg Psychiatry. doi:10.1136/jnnp-2017-316236