Natalizumab (NTZ) is approved for treatment of relapsing-remitting multiple sclerosis. Progressive multifocal leukoencephalopathy (PML) caused by the reactivation of the John Cunningham virus (JCV) is a safety concern with NTZ treatment.
To describe the long-term drug persistence in natalizumab JCV negative patients in a Swedish population-based setting.
The IMSE-1 study obtains demographic, clinical and safety data from the Swedish population-based Neuro Registry. Key inclusion criteria for this study were NTZ patients with a negative JCV values. Drug persistence was defined as the duration of time from initiation to discontinuation of therapy, estimated by the Kaplan-Meier approach, and Cox regression was used to identify possible independent factors related to drug discontinuation.
A total of 1177 NTZ patients were included,76% were female and the mean age at treatment start was 34.3 (SD 10.0) years. The mean treatment duration was 5.5 (SD 3.0) years. 57% of the patients switched to NTZ from interferons and Copaxone, 27% were treatment naïve, and 14% from other disease-modifying treatments. At 10 years following treatment initiation of NTZ 6.5% had discontinued due to lack of efficacy, 6.7%, 24.4% and 28.9% due to adverse events, pregnancy and other reasons, respectively. An increased EDSS score at baseline increased the risk of discontinuation due to the lack of effect (HR 1.30; 95% CI 1.04-1.62), but the opposite was true for SMDT at baseline (HR 0.97; 95% CI 0.95-0.99). Also, relapses during treatment initiation had a significant effect on the risk of discontinuation due to lack of efficacy (HR 1.67; 95% CI 1.31-2.11). Only calendar year of symptoms and calendar year of treatment initiation had a significant effect on drug discontinuation due to adverse events (HR 1.11; 95% CI 1.04-1.18, HR 1.25; 95% CI 1.10-1.41).
Data from the Swedish IMSE-1 study suggest that long-term drug discontinuation due to a lack of efficacy or adverse events are minimal, and that the most common reason for treatment discontinuation was due to pregnancy.
Funding: The IMSE-1 study is funded in a scientific collaboration agreement with Biogen.