VERISMO: A Post-Marketing Safety Study to Determine the Incidence of All Malignancies and Breast Cancer in Patients with Multiple Sclerosis Treated With Ocrelizumab

Objective: The primary objective of VERISMO is to estimate the incidence rate of all malignancies and breast cancer among patients with multiple sclerosis (MS) newly treated with ocrelizumab under routine clinical care. Background: During the Phase III clinical trials of relapsing and primary progressive MS, an imbalance in the incidence of malignancies was observed between the ocrelizumab and control arms, driven by an imbalance in numbers of female breast cancer events in the ocrelizumab group. Design/Methods: VERISMO is a multi-source, multi-country, noninterventional, longitudinal, observational, post-marketing safety study. Incidence rates of all malignancies/breast cancer will be compared between ocrelizumab-exposed patients and those newly treated with alternative approved MS disease-modifying therapies (DMTs), as well as general populations. Comparators include internal populations (patients with MS treated with alternative MS DMTs) and external populations (MSBase registry; Surveillance, Epidemiology and End Results Program). Inverse probability of treatment weights will be used to control for important baseline confounders, including age, sex, MS disease status, and cancer risk factors. The study will last 10 years, and patients will be followed for at least 5 years. Total patient years at risk will be calculated from the first ocrelizumab dose until the event, death, loss to follow-up, or end of study, whichever occurs first, irrespective of ocrelizumab exposure duration. Results: Planned enrollment in VERISMO includes 6,360 adult patients from the US and Germany: 4,000 ocrelizumab-treated and 2,360 treated with alternative MS DMTs. The sample size and study duration will provide sufficient precision around the incidence rates to address the primary objective. The minimum detectable hazard ratio with 80% power will be 1.46 for the rate of all malignancies and 2.00 for the rate of female breast cancer. Conclusions: The VERISMO post-marketing safety study will advance the understanding of any potential risk of malignancy/breast cancer in ocrelizumab-treated patients with MS. Disclosure: Dr. Wormser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche Ltd. Dr. Wormser has received compensation for serving on the Board of Directors of F. Hoffman-La Roche Ltd. Dr. Wormser has received research support from F. Hoffman-La Roche Ltd. Dr. Evershed has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche Ltd. Dr. Ferreira has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche Ltd. Dr. Stokmaier has nothing to disclose. Dr. Wang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffman-La Roche Ltd. Dr. Ziemssen has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer Healthcare, Biogen Idec, Novartis, Merck Serono, Teva, Genzyme, Synthon, Merck Sharp & Dohme, GlaxoSmithKline, Sanofi, and Almirall. Dr. Ziemssen has received research support from Bayer Healthcare, Biogen, Genzyme, Novartis, Teva, and Sanofi.