‘No new safety concerns’ emerge for ocrelizumab in MS subpopulations

Continuous administration of ocrelizumab in clinical trials and its broader use in real-world settings exhibited a favorable and manageable safety profile for relapsing MS and primary progressive MS, according to a study in Neurology.

Prior phase 2 and 3 studies outlined the safety and efficacy of ocrelizumab, leading to its approval for treating these patient populations; however, adverse events occurred.

“In controlled treatment periods of the pivotal phase 3 trials, infusion-related reactions, respiratory tract infections and urinary tract infections were the most common adverse events associated with [ocrelizumab],” study author Stephen L. Hauser, MD, of the department of neurology at the University of California, San Francisco, and colleagues wrote. “A numerical imbalance of malignancies was observed in patients treated with OCR relative to its comparators, mostly driven by a higher rate of breast cancer; overall, these events were uncommon. Safety surveillance to understand the long-term benefit–risk profile of OCR in patients with MS (PwMS) is therefore warranted.”

In the current analysis, the investigators reported the safety profile of ocrelizumab for up to 7 years among patients with relapsing MS and primary progressive MS who participated in clinical trials or received treatment in real-world post-marketing settings. They based safety analyses on integrated clinical and laboratory data of all patients who received ocrelizumab in 11 clinical trials, which included the controlled treatment and open-label extension periods of the phase 2 and 3 trials, as well as seven phase 3b trials. Further, they used additional post-marketing data for selected adverse events. The researchers used multiple epidemiologic sources to contextualize incidence rates of serious infections and malignancies.

Hauser and colleagues used a data cut-off date of January 2020 and included data of 5,680 patients with MS, with 18,218 who received ocrelizumab in clinical trials, with 18,218 patient-years of exposure. Results showed similar rates per 100 person years in the current analysis compared with those within the controlled treatment period of the phase 3 trials for adverse events (248), serious adverse events (7.3), infusion-related reactions (25.9) and infections (76.2). The researchers noted consistency between ranges reported in epidemiologic data and rates of the most common serious adverse events, including serious infections (2.01) and malignancies (0.46).

“No new safety concerns have emerged in a heterogeneous MS population (in more recent clinical trials and real-world settings) that includes early treatment-naive patients with relapsing-remitting multiple sclerosis, patients with [relapsing MS] previously treated with other [disease-modifying therapies (DMTs)], and patients with active secondary progressive [MS] or [primary progressive MS] who are older, more disabled and have a longer DMT history and higher number of comorbidities,” Hauser and colleagues wrote. “Long-term follow-up and post-marketing studies will continue to monitor the safety of long-term treatment with [ocrelizumab] in increasing numbers of patients.”