Pregnancy Exposure to Anti-CD20 Monoclonal Antibodies in Patients With Multiple Sclerosis

Background and ObjectivesAlthough anti-CD20 monoclonal antibodies (anti-CD20s) theoretically represent an ideal treatment option for women with multiple sclerosis (wwMS) planning a pregnancy, the paucity of real-world data still limits their use in this context. Through our Italian registry “CD20-PREGNANCY,” we aim to report pregnancy, infant, and maternal outcomes in wwMS treated with anti-CD20s. MethodsIn this observational study, wwMS having received rituximab (RTX), ocrelizumab (OCR), or ofatumumab (OFA) before and/or during pregnancy (≤12 months for RTX/OCR, ≤6 months for OFA) were included. Considering drug pharmacokinetics and timings of immunoglobulin placental transfer, pregnancies were classified as “exposed” (last administration pre-pregnancy ≤2.3 months for RTX, ≤3 for OCR, ≤1.8 for OFA) and “not-exposed” (last administration beyond these intervals) for comparative analysis. ResultsA total of 153 pregnancies (85 “not-exposed,” 68 “exposed”) across 27 Italian MS centers were collected. The median age at conception was 33.9 years (interquartile range 30.0–37.6) with 39.9% of women older than 35 years. Most pregnancies occurred in patients treated with OCR (77.1%). 80.4% of pregnancies ended in livebirth and 13.1% in spontaneous abortions (SA), without stillbirths/neonatal deaths. There was a significantly higher percentage of SA in “exposed” pregnancies than “not-exposed” (20.6% vs 7.1%, p = 0.014), but with values similar to those reported in general population. One serious perinatal infection (“exposed” group) and 2 major congenital anomalies (MCA) (one per group) were reported. Compared with the 12 months pre-pregnancy, annualized relapse rate remained stable during pregnancy but slightly increased postpregnancy (0.00 vs +0.09) in “not-exposed.” Conversely, it decreased in both periods (−0.02 vs −0.13) among “exposed”. Compared with pre-pregnancy, postpregnancy combined unique active lesions decreased in both groups (−0.15 in “not-exposed”, −0.38 in “exposed”), while 2 confirmed disability worsening were observed (“not-exposed”). DiscussionIn conclusion, a good control of disease activity was observed without an increased risk of MCA or perinatal infections. Percentages of SA were overall in line with those of general population, although with a higher proportion in the “exposed” group. These findings support the use of anti-CD20 therapies in wwMS planning pregnancy, although further data are needed to better define their safety profile in this setting.

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Journal
Neurology Neuroimmunology & Neuroinflammation
Published
2026-08-28
DOI
https://doi.org/10.1212/nxi.0000000000200650
Primary Topic
Multiple Sclerosis Research Studies
Type
article
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0.00

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article

Pregnancy Exposure to Anti-CD20 Monoclonal Antibodies in Patients With Multiple Sclerosis

Roberta Fantozzi, Massimo Filippi, Daniela Cargnelutti, Francesca Napoli et al.
Neurology Neuroimmunology & Neuroinflammation
Multiple Sclerosis Research Studies
article

Pregnancy Exposure to Anti-CD20 Monoclonal Antibodies in Patients With Multiple Sclerosis

Roberta Fantozzi, Massimo Filippi, Daniela Cargnelutti, Francesca Napoli, Angela Genchi, Lucia Moiola, Albulena Bajrami, Irene Gattuso, Carla Tortorella, Maria Cellerino, Massimiliano Mirabella, Laura Brambilla, Marco Vercellino, Elisabetta Signoriello, Isabella Righini, Doriana Landi, Laura Ghezzi, Emilio Portaccio, Maria Pia Amato, Lorena Lorefice, Roberta Lanzillo, Cristina Montomoli, Giovanna De Luca, Clara Grazia Chisari, Damiano Paolicelli, Matilde Inglese, Paola Cavalla, Francesco Patti, Vanessa Ziccone, Giovanna Borriello, Emanuela Susani, Maria A. Rocca, Assunta Bianco, Giacomo Lus, Antonio Gallo, Vincenzo Brescia Morra, Elena Colombo, Marco Zoccarato, Francesca Rinaldi, María Teresa Infante, Paola Perini, Valentina Gasparini, Pietro Annovazzi, Eleonora Cocco, for the CD20-Pregnancy Study Group, Carmine Esilio, Girolama Alessandra Marfia, Sebastiano Crisafulli, Maria Triassi
article en

Abstract

Background and ObjectivesAlthough anti-CD20 monoclonal antibodies (anti-CD20s) theoretically represent an ideal treatment option for women with multiple sclerosis (wwMS) planning a pregnancy, the paucity of real-world data still limits their use in this context. Through our Italian registry “CD20-PREGNANCY,” we aim to report pregnancy, infant, and maternal outcomes in wwMS treated with anti-CD20s. MethodsIn this observational study, wwMS having received rituximab (RTX), ocrelizumab (OCR), or ofatumumab (OFA) before and/or during pregnancy (≤12 months for RTX/OCR, ≤6 months for OFA) were included. Considering drug pharmacokinetics and timings of immunoglobulin placental transfer, pregnancies were classified as “exposed” (last administration pre-pregnancy ≤2.3 months for RTX, ≤3 for OCR, ≤1.8 for OFA) and “not-exposed” (last administration beyond these intervals) for comparative analysis. ResultsA total of 153 pregnancies (85 “not-exposed,” 68 “exposed”) across 27 Italian MS centers were collected. The median age at conception was 33.9 years (interquartile range 30.0–37.6) with 39.9% of women older than 35 years. Most pregnancies occurred in patients treated with OCR (77.1%). 80.4% of pregnancies ended in livebirth and 13.1% in spontaneous abortions (SA), without stillbirths/neonatal deaths. There was a significantly higher percentage of SA in “exposed” pregnancies than “not-exposed” (20.6% vs 7.1%, p = 0.014), but with values similar to those reported in general population. One serious perinatal infection (“exposed” group) and 2 major congenital anomalies (MCA) (one per group) were reported. Compared with the 12 months pre-pregnancy, annualized relapse rate remained stable during pregnancy but slightly increased postpregnancy (0.00 vs +0.09) in “not-exposed.” Conversely, it decreased in both periods (−0.02 vs −0.13) among “exposed”. Compared with pre-pregnancy, postpregnancy combined unique active lesions decreased in both groups (−0.15 in “not-exposed”, −0.38 in “exposed”), while 2 confirmed disability worsening were observed (“not-exposed”). DiscussionIn conclusion, a good control of disease activity was observed without an increased risk of MCA or perinatal infections. Percentages of SA were overall in line with those of general population, although with a higher proportion in the “exposed” group. These findings support the use of anti-CD20 therapies in wwMS planning pregnancy, although further data are needed to better define their safety profile in this setting.

Neurology Neuroimmunology & NeuroinflammationVol. 13(6)
Università Cattolica del Sacro Cuore (IT), University of Rome Tor Vergata (IT), Vita-Salute San Raffaele University (IT), University of Campania "Luigi Vanvitelli" (IT), University of Pavia (IT), Agostino Gemelli University Polyclinic (IT), Istituto Neurologico Mediterraneo (IT), University of Catania (IT), University of Chieti-Pescara (IT), Ospedale Santa Chiara (IT), Associazione Italiana Sclerosi Multipla (IT), Fatebenefratelli Hospital (IT), ATS Sardegna (Italy) (IT), Don Carlo Gnocchi Foundation (IT), University of Campania "Luigi Vanvitelli" (IT), Nini Hospital (LB), Azienda Ospedale - Università Padova (IT), Ospedale SS. Annunziata (IT), Carlo Forlanini Hospital (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Neurologico Carlo Besta (IT), Ospedale San Pietro Fatebenefratelli (IT), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University of Florence (IT), University of Turin (IT), University of Bari Aldo Moro (IT), University of Naples Federico II (IT), University of Genoa (IT)
Biogen
Good health and well-being
Openalex Percentile: Top 11%
Multiple Sclerosis Research Studies
DOIOpen Access PDFOpenAlex
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