Ongoing safety reporting is crucial to understanding the long-term benefit–risk profile of ocrelizumab (OCR) in patients with multiple sclerosis (MS). The safety and efficacy of OCR have been characterised in one Phase II study in relapsing-remitting MS (NCT00676715), two identical Phase III trials in relapsing MS (RMS; OPERA I/II [NCT01247324]/[NCT01412333]) and the Phase III trial in primary progressive MS (PPMS; ORATORIO [NCT01194570]).
Safety outcomes were reported for all patients who received OCR during the controlled treatment and associated OLE periods of the Phase II and Phase III clinical trials, plus the ongoing Phase IIIb trials VELOCE, CHORDS/CASTING, OBOE, ENSEMBLE and associated substudies (OCR all-exposure population). The number of post-marketing patients exposed to OCR is based on estimated total number of vials sold, as well as US claims data. To account for the different exposure lengths, the incidence rate per 100 patient years (PY) is presented. Adverse events (AEs) were classified according to the Medical Dictionary for Regulatory Activities.
As of July 2018, 4,501 patients with MS received OCR in clinical trials resulting in 12,559 PY of exposure. Reported rates per 100 PY in the OCR all-exposure population (95% confidence interval) were as follows: AEs, 255 (252–258); serious AEs, 7.52 (7.05–8.02); infections, 77.1 (75.5–78.6); serious infections, 2.01 (1.77–2.27); malignancies, 0.47 (0.36–0.61); and AEs leading to treatment discontinuation, 1.15 (0.97–1.35). As of April 2019, approximately 96,000 patients with MS have initiated OCR globally in the post-marketing setting and the data remain generally consistent with that observed in clinical trials. Updated OCR all-exposure population data using a January 2019 cut-off and selected post-marketing data will be presented.
The reported rates of events per 100 PY in the ocrelizumab all-exposure clinical trial population and post-marketing settings continue to be generally consistent with those seen during the controlled treatment period in the RMS and PPMS populations. The rate of AEs leading to treatment discontinuation also remained stable with additional patient exposure. Long-term safety data will continue to be reported on a regular basis.
© 2019 Published by Elsevier Inc.