Updated Incidence of Progressive Multifocal Leukoencephalopathy in Natalizumab-Treated Multiple Sclerosis Patients Stratified by Established Risk Factors (S41.001)

Objective: To quantify progressive multifocal leukoencephalopathy (PML) risk in multiple sclerosis (MS) patients considering or receiving natalizumab using three risk factors: anti-JC virus (JCV) antibody positive serostatus, prior immunosuppressant use, and natalizumab treatment duration. Background PML, an opportunistic brain infection caused by JCV, occurs primarily in patients who are immunocompromised or have received immunomodulatory therapies, such as natalizumab. Anti-JCV antibody positive status, prior immunosuppressant use, and natalizumab treatment duration are PML risk factors in natalizumab-treated patients. Design/Methods: Data from natalizumab postmarketing sources and clinical studies were used to estimate PML incidence in natalizumab-treated MS patients by anti-JCV antibody status (positive or negative), prior immunosuppressant use (yes or no), and duration of natalizumab treatment (1–24 or 25–48 months). Results: As of September 2011, 159 PML cases were confirmed among 92,105 patients exposed to natalizumab in the postmarketing setting. PML risk was lowest in anti-JCV antibody negative patients (estimated at ≤0.10 per 1000 [95%CI:0–0.56] or ≤0.17 per 1000 [95%CI:0.00–0.94], assuming one hypothetical PML case testing anti-JCV antibody negative prior to diagnosis, and exposures ≥1 natalizumab dose or ≥18 natalizumab doses, respectively). PML risk was highest in patients with all three risk factors, anti-JCV antibody positive status, prior immunosuppressant use, and 25–48 months of natalizumab treatment (9.8 per 1000; 95%CI:7.0–13.4). Conclusions: This analysis, representing approximately 178,000 patient-years of natalizumab experience, demonstrates that discrete MS subpopulations can be identified at greater or lesser PML risk based upon the presence or absence of risk factors using an algorithm capable of discerning an approximate 100-fold difference in risk between the highest and lowest risk groups. The use of anti-JCV antibody status in this quantitative algorithm marks the first use of a safety biomarker for risk stratification to inform treatment decisions in MS. Studies are ongoing to further characterize the PML risks presented in this analysis. Supported by: Biogen Idec Inc. and Elan Pharmaceuticals, Inc. Disclosure: Dr. Bloomgren has received personal compensation for activities with Biogen Idec as an employee. Dr. Richman has received personal compensation for activities with Biogen Idec as employees.Dr. Richman holds stock and/or options in Biogen Idec, which sponsored research in which Dr. Richman was involved as an investigator. Dr. Hotermans has received personal compensation for activities with Biogen Idec as an employee.Dr. Hotermans holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Hotermans was involved as an investigator. Dr. Subramanyam has received personal compensation for activities with Biogen Idec as an employee. Dr. Subramanyam holds stock and/or stock options in Biogen Idec. Dr. Natarajan has received personal compensation for activities with Biogen Idec as an employee. Dr. Lee has received personal compensation for activities with Biogen Idec as an employee. Dr. Plavina has received personal compensation for activities with Biogen Idec as an employee.Dr. Plavina holds stock and/or stock options in Biogen Idec which sponsored research in which Dr. Plavina was involved as an investigator. Dr. Scanlon has received personal compensation for activities with Biogen Idec as an employee. Dr. Sandrock has received personal compensation for activities with Biogen Idec as an employee. Dr. Sandrock holds stock and/or stock options in Biogen Idec. Dr. Bozic has received personal compensation for activities with Biogen Idec. Dr. Bozic holds stock and/or stock options in Biogen Idec, which sponsored research in which Dr. Bozic was involved as an investigator. Dr. Bozic holds stock and/or stock options in Biogen Idec.