Pregnancy Outcomes in Ofatumumab-Treated Women Appear Consistent With General Population Rates

Investigators recently reported cumulative data on pregnancy and infant outcomes among women with relapsing multiple sclerosis (MS) who were treated with ofatumumab (Kesimpta; Novartis), an FDA-approved disease-modifying therapy, during or shortly before pregnancy. Presented at the 2025 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 28-31, 2025, in Phoenix, Arizona, researchers noted that the outcomes appeared consistent with background rates observed in the general population.¹

The analysis included data from the Novartis Global Safety Database, drawing on cases from clinical trials and post marketing surveillance via the PRegnancy outcomes Intensive Monitoring program (PRIM). As of September 25, 2024, researchers identified a total of 669 prospective pregnancy cases. Among the 275 cases reported at least 1 year prior to the data cutoff, exposure details were available from 221 women. Of those, 12% received ofatumumab in 180 days before their last menstrual period, 87% were exposed during the first trimester, and 0.5% after the first trimester.

Presented by lead author Riley Bove, MD, an associate professor of neurology at the University of California, San Francisco, pregnancy outcomes were known for 103 of the 275 cases. Of these cases, researchers reported that 73 (70.9%) resulted in live births, whereas 13 (12.6%) were induced terminations, including 1 related to a chromosomal anomaly, and 13 (12.6%) were spontaneous abortions. Notably, investigators identified 1 case each of a spontaneous abortion not otherwise specified (1.0%) and stillbirth (1.0%), and 2 cases of ectopic pregnancies (1.9%).

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Additional findings of the study revealed that minor congenital anomalies were reported in 2 infants, specifically hemangioma and hydronephrosis. One major congenital malformation, truncus arteriosus persistent, was also reported in a case added after the 1-year analysis period, post September 25, 2023. Although the number of cases were limited, the results suggest that the prevalence of pregnancy outcomes following maternal ofatumumab administration during or shortly before pregnancy may be in line with expected rates in the general population.

Ofatumumab, approved to treat relapsing forms of MS, has been on the market since 2021. It acts as a fully-humanized monoclonal anti-CD20 antibody constructed with recombinant DNA techniques and is designed to selectively target CD20-expressing B-cells. Following cell surface binding, ofatumumab selectively depletes CD20-expressing B-cells through antibody-dependent cellular phagocytosis, antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and apoptosis.

The subcutaneous injection therapy was approved by the FDA in 2020 based on data from ASCLEPIOS I and II. The studies, which feature more than 1800 patients, pitted the agent against teriflunomide, an oral inhibitor of pyrimidine synthesis that reduces T-cell and B-cell activation. In the studies results showed a 51% reduction in annualized relapse rate (ofatumumab: 0.11; teriflunomide: 0.22; difference, −0.11; 95% CI, −0.16 to −0.06; P <.001) in ASCLEPIOS I and 58% (ofatumumab: 0.10; teriflunomide: 0.25; difference, −0.15; 95% CI, −0.20 to −0.09; P <.001) reduction in ASCLEPIOS II in those who received ofatumumab.^2,3

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REFERENCES
1. Bove R, Stoll S, Amato MP, et al. Pregnancy and Infant Outcomes in Women with Relapsing Multiple Sclerosis Following Exposure to Ofatumumab: Update from the Prim Study. Presented at: 2025 CMSC Annual Meeting; May 28-31; Phoenix, AZ. ABSTRACT LBA14.
2. FDA approves Novartis Kesimpta® (ofatumumab), the first and only self-administered, targeted B-cell therapy for patients with relapsing multiple sclerosis. News release. Novartis. August 20, 2020. Accessed May 28, 2025. https://www.globenewswire.com/news-release/2020/08/20/2081597/0/en/FDA-approves-Novartis-Kesimpta-ofatumumab-the-first-and-only-self-administered-targeted-B-cell-therapy-for-patients-with-relapsing-multiple-sclerosis.html
3. Hauser SL, Bar-Or A, Cohen JA, et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med. 2020;383:546—557. doi: 10.1056/NEJMoa1917246