Pregnancy and Infant Outcomes Remain Unchanged With Multiple Sclerosis Therapy Ocrelizumab

In the largest data set of pregnancy outcomes for an anti-CD20 therapy in patients with multiple sclerosis (MS), results showed that in utero exposure to ocrelizumab (Ocrevus; Genentech) did not increase the risk of adverse pregnancy or infant outcomes. These data demonstrating ocrelizumab’s safety are significant considering pregnancies may occur during the 6-month interval between infusions.

These data were presented at the 2024 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 29 to June 2, in Nashville, Tennessee, by Riley Bove, MD, an associate professor of neurology at the University of California, San Francisco. Using the Roche safety database, 3244 cumulative MS pregnancies were received; 2444 were reported prospectively, 793 retrospectively, and 7 unspecified. Of the prospective pregnancies, 855 (35.0%) had in utero exposure, 574 (23.5%) had no in utero exposure, and 1015 (41.5%) had unknown exposure.

Maternal ocrelizumab exposure was defined as at least 1 infusion, while potential in utero exposure was defined as less than 3 months prior to the last menstrual period or during pregnancy. Fetal death was termed spontaneous abortion (SA) If there was less than 22 complete gestational weeks (GW) or still birth (SB) if later. Among the 1144 prospective pregnancies for which outcomes were known, 83.6% were live births (LBs), 14 (1.2%) were ectopic pregnancies (EP), 58 (5.1%) were elective terminations (ET), 115 (10.1%) were SA, and 1 (0.1%) were SB.

Of the LBs recorded, 586 (61.3%) were full-term, 82 (8.6%) were preterm, and 288 (30.1%) had unknown GW. Of the 855 prospective pregnancies exposed in utero, 512 had known outcomes. Here, results showed that 84.2% were LB, 4 (0.8%) EP, 38 (7.4%) ET, 38 (7.4%) SA, and 1 (0.2%) SB. Sixteen (1.7%) major congenital abnormalities (MCAs) occurred in prospective LB, 9 of which had in utero exposure.

READ MORE: Gaining Clinical Insights Into the Benefits of Subcutaneous Ocrelizumab

Ocrelizumab has been FDA-approved since 2017 and remains the only marketed therapy to treat patients with primary progressive MS. Its original approval was for an intravenous infusion, supplied in 300 mg/mL single-dose vials. The initial dose is given as a 300 mg intravenous infusion over 2.5 hours, followed up with an additional 300 mg intravenous infusion 14 days later. Subsequent doses are given every 6 months as a 600 mg intravenous infusion over 3.5 hours.

More recently, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended approval for a subcutaneous administration of ocrelizumab to treat both progressive and relapsing MS. The decision, expected to come mid-2024, will be based on data from the phase 3 OCARINA 2 trial (NCT05232825). In that global, randomized study, a 920-mg subcutaneous dose formulation of ocrelizumab was comparable to its 300-mg intravenous counterpart in terms of clinical benefit.

The belief is that if approved, a SC administration of ocrelizumab will provide treatment flexibility and additional treatment options for patients and healthcare providers. In OCARINA, the SC and IV administration led to similar exposure overall during the first 12 weeks of treatment for the 116 patients who received each therapy in the study, with a geometric mean ratio comparing both arm’s area under the curve (AUC) of 1.29 (90% CI, 1.23-1.35; subcutaneous AUC weeks 1-12, 3500 µg/mL per day; IV AUC weeks 1-12, 2750 µg/mL per day).

Earlier this year, at the 2024 American Academy of Neurology (AAN) Annual Meeting, Bove sat down with NeurologyLive® to discuss the findings related to pregnancy outcomes in women exposed to ocrelizumab. In the interview, she provided context on the areas that may need further data collection and monitoring, especially concerning infant outcomes. Through the link below, she talked about suggested recommendations for healthcare professionals based on the study’s results.

REFERENCES
1. Bove R, Pietrasanta C, Oreja-Guevara C, et al. Pregnancy and infant outcomes in females receiving ocrelizumab for the treatment of multiple sclerosis: analysis of over 3000 pregnancies to date. Presented at: 2024 CMSC Annual Meeting; May 29-June 2; Nashville, TN. Abstract DMT05
2. Roche’s OCREVUS subcutaneous injection receives EU CHMP positive opinion for relapsing and primary progressive multiple sclerosis. News release. Roche. April 29, 2024. Accessed May 28, 2024. https://www.roche.com/investors/updates/inv-update-2024-04-29
3. Newsome SD. Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase III OCARINA II Study. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER P370.