Pregnancy Exposure to Anti-CD20 Monoclonal Antibodies in Patients With Multiple Sclerosis: Results From an Italian Multicenter Registry Study

Background and objectives: Although 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. Methods: In 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. Results: A 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"). Discussion: In 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.