199 Changes in natalizumab exposure and PML incidence over time

Introduction Since the identification in 2012 of three risk factors for natalizumab-associated progressive multifocal leukoencephalopathy (PML), changes in the PML incidence rate have been of interest. Methods The incidence of confirmed PML cases in Biogen’s postmarketing global safety database from November 2009 to November 2017 was evaluated retrospectively. Overall incidence in natalizumab-exposed patients was determined by the estimated total number of patients exposed and the number of confirmed cases. Changes in exposure patterns over time were evaluated by 12-infusion epochs. Results As of 30 November 2017, 180,656 patients worldwide had received ≥1 dose; overall natalizumab-associated PML incidence was 4.19/1000 patients. Since mid-2016, overall monthly incidence of PML appears to have stabilised, remaining between 4.18 and 4.24/1000. PML incidence was greatest in later, higher risk infusion epochs (≥37 infusions). The relative increase in the proportion of patients in higher-exposure epochs (u003e24 infusions) has declined from 2013 to 2017. Conclusions The stabilisation of overall natalizumab-associated PML incidence beginning mid-2016 coincides with the introduction of a new risk algorithm, suggesting that risk stratification factors are being incorporated into clinical practice and may continue to impact future incidence. Support: Biogen. Disclosures to be included on poster.