DX46
Safety of Ocrelizumab in Multiple Sclerosis: Updated Analysis in Patients with Relapsing and Primary Progressive Multiple Sclerosis
The safety and efficacy of ocrelizumab has been characterized in Phase III trials in relapsing multiple sclerosis (RMS; OPERA I and OPERA II) and primary progressive MS (PPMS; ORATORIO). Ongoing safety reporting on disease-modifying therapies for MS is crucial to understanding the long-term benefit-risk profile.
Objectives:
To report updated safety data from the controlled and open-label extension (OLE) periods of the clinical trials of ocrelizumab in RMS and PPMS.
Methods:
The OPERA studies randomized patients (1:1) to ocrelizumab 600 mg every 24 weeks or subcutaneous interferon beta-1a (IFN β-1a) 44 μg three times weekly for 96 weeks. ORATORIO randomized patients (2:1) to ocrelizumab 600 mg or placebo every 24 weeks for at least 120 weeks. Phase III patients completing the controlled treatment period could enter an ocrelizumab OLE phase. A Phase II study in relapsing-remitting MS randomized patients (1:1:1:1) to ocrelizumab 600 mg, ocrelizumab 2000 mg, placebo or intramuscular IFN β-1a through Week 24, followed by ocrelizumab every 24 weeks through Week 96; after a treatment-free period, eligible patients entered a long-term OLE in which ocrelizumab 600 mg was administered every 24 weeks. Safety outcomes were reported for all patients dosed with ocrelizumab in Phase II and III MS clinical trials, including patients who switched to ocrelizumab from comparators.
Results:
As of 20 January 2016, 2279 patients with MS received ocrelizumab, resulting in 5711 patient-years (PY) of exposure. Reported rates per 100 PY (95% CI) were as follows: adverse events (AEs), 242 (238–246); serious AEs, 6.97 (6.30–7.69); infections, 73.6 (71.4–75.9); and serious infections, 1.80 (1.47–2.19). The incidence rate of malignancy was 0.440 (0.285–0.649). A June 2016 data cut available for malignancies showed an incidence rate of 0.402 (0.263–0.589).
Conclusions:
The updated safety profile in the ocrelizumab MS all-exposure population is generally consistent with that seen during the controlled treatment period in the RMS and PPMS populations. Additional data from ongoing follow-up will be reported.