Research Finds In Utero Exposure to Ocrelizumab Not Associated With Increased Adverse Pregnancy, Infant Outcomes for Women With MS
This is the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS, enabling a more comprehensive understanding of ocrelizumab’s safety.
New research findings presented at the Consortium of Multiple Sclerosis Centers 2024 Annual Meeting found that in utero exposure to ocrelizumab (Ocrevus; Genentech) was not associated with an increased risk of adverse pregnancy or infant outcomes compared with the epidemiologic background of both multiple sclerosis (MS) as well as the general population.
Family planning is an important issue for many patients with MS, and newer medications are making pregnancy safer and more possible for this patient population. Additionally, presenter Riley Bove, MD, said there is a growing body of evidence surrounding the safe use of high-efficacy disease modification therapies (DMTs), including anti-CD20 agents, during pregnancy and breastfeeding.
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More than 300,000 patients globally have initiated treatment with ocrelizumab as of March 2023, and it is supported by strong clinical and real-world evidence of efficacy and safety. However, reports of infant outcomes after exposure to ocrelizumab are limited.
“Potential risks to the woman and the fetus must really be balanced with maintenance and management of multiple sclerosis,” Bove said. “Indeed, disease stabilization before, during, and after pregnancy can help reduce the risk of postpartum rebound relapses, and this can be achieved through appropriate selection and timing of DMTs.”
Prescribing information for ocrelizumab specifies that patients should use contraception while receiving the drug and for 6 months after the last infusion. However, Bove noted that pregnancies can still occur during this time. To better understand pregnancy and infant outcomes among women with MS receiving ocrelizumab before or during pregnancy, as well as while breastfeeding, investigators utilized data from the Roche safety database.
Maternal ocrelizumab exposure was defined as 1 or more infusions and potential in utero exposure was defined as 3 months or less prior to the last menstrual period or during pregnancy. As of July 12, 2023, 3244 cumulative pregnancies among women with MS were received, including 2444 reported prospectively, 793 reported retrospectively, and 7 unspecified. Of the 2444 prospective pregnancies, 855 (35%) had in utero exposure, 574 (23.5%) had no in utero exposure, and 1015 (41.5%) had unknown exposure.
The outcomes were known for 1144 prospective pregnancies, of which 956 (83.6%) were live births (61.3% full-term, 8.6% preterm, 30.1% unknown), 14 (1.2%) were ectopic pregnancies, 58 (5.1%) underwent elective terminations, 115 (10.1%) resulted in spontaneous abortion (defined as miscarriage at less than 22 weeks’ gestation), and 1 (<0.1%) was a stillbirth. Of the 955 prospective pregnancies with in utero exposure, 512 had known outcomes, 431 (84.2%) of which were live births, 4 (0.8%) were ectopic pregnancies, 38 (7.4%) were elective terminations, 38 (7.4%) resulted in spontaneous abortion, and 1 (0.2%) was a stillbirth.
Interestingly, Bove noted that a higher proportion of elective terminations occurred in the group with in utero exposure to ocrelizumab, although the overall cumulative proportion of elective abortions has decreased in recent years, from 12.7% in 2021 to 7.4% in 2023.
“So, overall, exposure to ocrelizumab was not associated with an increased risk of adverse pregnancy or infant outcomes compared with the epidemiologic background of both MS and the general population,” Bove said.
Sixteen (1.7%) major congenital anomalies occurred in prospectively reported live births, 9 of which had in utero exposure. These anomalies included 5 urinary defects (27.8%) and 5 congenital heart defects (27.8%), as well as 2 limb anomalies, 2 chromosomal anomalies, and 1 each ocular anomaly, oro-facial cleft, digestive system anomaly, and genital anomaly. Bove noted that similar background rates have been reported in both patients with MS (2.2% to 4.2%) and the general population (2% to 4.4%).
Based on these findings, Bove said the investigators concluded that in utero exposure to ocrelizumab was not associated with heightened risk of adverse pregnancy or infant outcomes, and the pattern of major congenital abnormalities reported was consistent with epidemiologic data. Because immunoglobulin Gs are not known to cross the placenta in the first trimester, Bove said the risk of congenital malformations is expected to be low.
She noted that this is the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS, enabling a more comprehensive understanding of ocrelizumab’s safety. However, she urged health care providers to continue reporting pregnancy and infant outcomes for this patient population.
“Reporting by health care professionals remains a critical component to increase available evidence, since complete reports of infant outcomes upon exposure to ocrelizumab throughout the first year of life are very limited,” Bove concluded.
