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. 2025 Jan;12(1):e200349.
doi: 10.1212/NXI.0000000000200349. Epub 2024 Dec 17.

Pregnancy and Infant Outcomes in Women With Multiple Sclerosis Treated With Ocrelizumab

Sandra Vukusic  1   2   3   4 , Riley Bove  5 , Ruth Dobson  6 , Thomas McElrath  7 , Celia Oreja-Guevara  8   9 , Carlo Pietrasanta  10   11 , Chien-Ju Lin  12 , Germano Ferreira  13 , Licinio Craveiro  13 , Dusanka Zecevic  13 , Noemi Pasquarelli  13 , Kerstin Hellwig  14
Affiliations

Pregnancy and Infant Outcomes in Women With Multiple Sclerosis Treated With Ocrelizumab

Sandra Vukusic et al. Neurol Neuroimmunol Neuroinflamm. 2025 Jan.

Abstract

Background and objectives: Ocrelizumab labeling advises contraception for women during treatment and for 6-12 months thereafter. Because pregnancies may occur during this time, it is critical to understand pregnancy and infant outcomes in women with multiple sclerosis (MS) after ocrelizumab exposure.

Methods: Pregnancy cases reported to Roche global pharmacovigilance until 12 July 2023 were analyzed. In utero exposure was defined if the last ocrelizumab infusion occurred in the 3 months before the last menstrual period or during pregnancy. Breastfeeding exposure was defined if at least one infusion occurred while breastfeeding. Fetal death was termed spontaneous abortion (SA) if < 22 complete gestational weeks (GWs) and stillbirth if later. Live births (LBs) were preterm if < 37 complete GWs. Major congenital anomalies (MCAs), infant outcomes, and maternal complications were also analyzed.

Results: In total, 3,244 pregnancies were reported in women with MS receiving ocrelizumab. The median maternal age was 32 years (Q1-Q3: 29-35 years), and most women had relapsing MS (65.6%). Of 2,444 prospectively reported pregnancies, 855 were exposed to ocrelizumab in utero (512 with a known outcome), 574 were nonexposed, and the remaining 1,015 had unknown timing of exposure. Most (83.6%; 956/1,144) of the pregnancies with a known outcome resulted in LBs (exposed, 84.2%; nonexposed, 88.3%). The exposed and nonexposed groups had similar proportions of other important pregnancy outcomes (preterm births, 9.5% vs 8.7%; SA, 7.4% vs 9.1%). Elective abortions were more frequent in the exposed group (7.4%, vs 1.7% in the nonexposed group). The proportion of LBs with MCAs was similar between the exposed and nonexposed groups (2.1% vs 1.9%) and within epidemiologic background rates. In the exposed group, one stillbirth and one neonatal death were prospectively reported.

Discussion: In this analysis of a large pregnancy outcome dataset for an anti-CD20 in MS, in utero exposure to ocrelizumab was not associated with an increased risk of adverse pregnancy or infant outcomes. These data will enable neurologists and women with MS to make more informed decisions around family planning, balancing safety risks to the fetus/infant against the importance of disease control in the mother.

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Conflict of interest statement

S Vukusic received grants and research support from Biogen, Novartis, Merck-Serono, F. Hoffmann-La Roche Ltd and Sanofi-Genzyme; consulting fees from F. Hoffmann-La Roche Ltd, Biogen, BMS-Celgene, Janssen, Novartis, Merck-Serono, Sandoz, Sanofi-Genzyme and Teva; and payment/honoraria for lectures, speaking etc. from F. Hoffmann-La Roche Ltd, Biogen, BMS-Celgene, Novartis, Merck-Serono, Sandoz, Sanofi-Genzyme and Teva. R Bove received research support from the National Institutes of Health, National Multiple Sclerosis Society, Hilton Foundation, California Initiative to Advance Precision Medicine, Tom Sherak Foundation, Biogen, Novartis and F. Hoffmann-La Roche Ltd/Genentech; and personal compensation for consulting from Alexion, Biogen, EMDSerono, Novartis, Sanofi-Genzyme, F. Hoffmann-La Roche Ltd/Genentech and TG Therapeutics. R Dobson received research support from Multiple Sclerosis Society UK, Horne Family Foundation, Barts Charity, Merck, Biogen and Celgene; consulting fees from F. Hoffmann-La Roche Ltd, Novartis, Janssen and Biogen (all payments made are institutional and used to support research/educational activities); honoraria for lectures, speaking etc. from Biogen, F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck, Novartis, Janssen and Teva; and support for attending meetings and/or travel from Novartis, Biogen and Janssen (all payments made are institutional and used to support research/educational activities) and is a member of the Association of British Neurologists MS Advisory Group and NHSE Neurology CAG. T McElrath received research support from the National Institutes of Health and NX Prenatal Inc.; compensation for service on the scientific advisory boards of NX Prenatal Inc., Mirvie Inc., F. Hoffmann-La Roche Ltd.; and consulting fees from F. Hoffmann-La Roche Ltd and Comanche Biopharma. C Oreja-Guevara received honoraria for consulting and serving on advisory boards from Biogen Idec., F. Hoffmann-La Roche Ltd, Sanofi-Genzyme, Merck, Novartis, BMS, Viatris, Janssen, Alexion, Horizon, and Teva Genzyme, Merck, Novartis and Teva. C Pietrasanta received consulting fees from F. Hoffmann-La Roche Ltd. C-J Lin is an employee of and shareholder in F. Hoffmann-La Roche Ltd. G Ferreira is a consultant for F. Hoffmann-La Roche Ltd. L Craveiro is an employee of and shareholder in F. Hoffmann-La Roche Ltd. D Zecevic is an employee of and shareholder in F. Hoffmann-La Roche Ltd. N Pasquarelli is an employee of and shareholder in F. Hoffmann-La Roche Ltd. K Hellwig received grant/contract support, consulting fees, honoraria and/or compensation from the Federal Innovationsfonds, National MS Society in Germany, Almiral Bayer, Biogen, Sanofi, Teva, F. Hoffmann-La Roche Ltd, Novartis and Merck. Go to Neurology.org/NN for full disclosures.

Figures

Figure 1
Figure 1. Pregnancies Reported in Women With Multiple Sclerosis Exposed to Ocrelizumab, by Year
Columns represent the cumulative number of pregnancies in women with MS exposed to ocrelizumab in each year of analysis (numbers in bold above each column). For each year, the cumulative previously reported pregnancies are shaded dark blue and those newly reported in that year are shaded light blue. The analysis period for each year extended from the day after the previous clinical cutoff date (CCOD) up to that year's CCOD, as follows: 2017 (no previous CCOD), till 31 January 2017; 2018, till 31 March 2018; 2019, till 31 March 2019; 2020, till 27 March 2020; 2021, till 31 March 2021; 2022, till 31 March 2022; 2023, till 12 July 2023. Note that of the cumulative total of 3,244, 91% (3,244-267 = 2,977) of cases were reported after the 2019 CCOD, i.e., after 31 March 2019.
Figure 2
Figure 2. Multiple Sclerosis Pregnancies by In Utero Exposure: All Cases and Prospective Cases
IgG1 = immunoglobulin G1; LMP = last menstrual period; OCR, ocrelizumab; t½, half-life. aDetermined according to timing of the last OCR dose in relation to the date of LMP (months); exposure classification is based on OCR t½ = 26 days (full elimination from the body is expected by approximately 4.5 months) and assuming that no relevant placental transfer of IgG1 antibodies occurs before 12 weeks of gestation. Percentages displayed in parentheses above the bars are proportions of the total exposed or nonexposed cases (for all cases or prospective cases, as applicable; ‘n's are shown at the bottom of the figure).
Figure 3
Figure 3. Incidence of Major Congenital Anomalies by EUROCAT 1.5 Anomaly Class
The graphic represents the reported number of major congenital anomalies in each EUROCAT 1.5 anomaly class, for prospectively reported cases and for all cases. Percentages are proportions of the total number of anomalies reported in each class.
See this image and copyright information in PMC

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