B-Cell Depletion Persists Into Third Trimester After Ofatumumab Cessation, Real-World MS Cohort Finds

A small observational study recently published in the Multiple Sclerosis Journal offered some of the first real-world data on B-cell kinetics and postpartum disease activity in women with relapsing-remitting multiple sclerosis (MS) who paused ofatumumab (Kesimpta; Novartis) at conception. Findings indicated that B-cell depletion persisted well into the third trimester, despite a treatment gap of approximately 9 months, and that postpartum MS activity remained low in this cohort, with no relapses recorded across all 25 participants.¹

These results potentially address a practical clinical gap since ofatumumab labeling recommends contraception for up to 6 months following the last dose, but in real-world practice the agent is typically discontinued upon confirmed pregnancy, in line with Association of British Neurologists guidance.^1,2 The authors noted that this possibly creates uncertainty about residual B-cell suppression during pregnancy and the optimal strategy, maintenance dosing versus reloading, for postpartum reinitiation.

Study Overview

Senior author Wallace Brownlee, MBChB, PhD, FRACP, a neurologist at Cleveland Clinic London, and colleagues conducted a retrospective observational study of women with relapsing-remitting MS managed at the MS Family Planning and Pregnancy Clinic at the National Hospital for Neurology and Neurosurgery, London. Inclusion required at least 1 ofatumumab injection prior to pregnancy, confirmed treatment pause following a positive home pregnancy test, a completed live birth between December 2023 and November 2025, and available postpartum clinical and MRI follow-up.

Women with miscarriages or an intrapartum switch to another disease-modifying therapy (DMT) were excluded. The final cohort comprised 25 women with a mean maternal age of 33.4 years and a mean MS disease duration of 7 years, of whom 52% had switched to ofatumumab from a prior disease-modifying therapy. The primary objectives of the study were to characterize third-trimester CD19 counts, postpartum MS activity, and pregnancy outcomes.

Key Findings

Third-trimester absolute CD19 counts were available for 23 of 25 women in the analysis. All remained B-cell depleted, with a median CD19 of 0.017 × 10⁹/L (range: 0.000–0.087), measured at a mean of 8 months after the last ofatumumab dose. B-cell depletion was defined using the threshold of less than 0.110 × 10⁹/L, corresponding to the lower limit of normal and the cutoff applied in the MIRROR trial.

No postpartum relapses were observed (0/25; 100% relapse-free). Most women (22/25; 88%) showed no new MRI activity postpartum. Three women (12%) had new T2 lesions; however, none had undergone re-baseline MRI after initiating ofatumumab, so these findings were interpreted as new baseline rather than breakthrough activity. Notably, authors noted that third-trimester CD19 counts in all 3 were below the lower limit of normal.

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All told, ofatumumab was restarted in 24 of 25 women at a median of 3 weeks postpartum, with 71% reinitiated in 4 weeks. The majority (75%) resumed monthly maintenance dosing; 25% received loading doses, either per clinical protocol or on physician recommendation. Treatment was paused for a mean of 9.2 months before resumption. One woman elected to defer restarting while breastfeeding.

All 25 pregnancies resulted in live singleton births. Twenty infants (80%) were born at term, and 19 women (76%) breastfed. Authors also noted that no new maternal or infant safety signals were attributed to ofatumumab by the treating neurologists.

Clinical Context

Women with MS face elevated relapse risk in the postpartum period, a phenomenon well documented since the PRIMS cohort.³ Anti-CD20 therapies such as ofatumumab selectively deplete CD20-expressing B cells, providing durable suppression of relapsing disease activity, but their long half-life and sustained pharmacodynamic effects complicate peripartum management.² Physiological reductions in circulating B cells during pregnancy add a further layer of complexity in interpreting CD19 counts and informing reinitiation decisions.⁴ Prior data from ocrelizumab (Ocrevus; Genentech) and rituximab cohorts have suggested relatively favorable postpartum outcomes with anti-CD20 therapy.⁵

Interpretation

The finding that B-cell depletion persisted into the third trimester, well beyond the labeling-recommended contraception window, suggested that the combined effects of ofatumumab's sustained mechanism and pregnancy-related B-cell decline may provide continued immunologic suppression even after treatment is stopped. The low rates of postpartum relapse and new MRI activity are clinically encouraging, though the authors appropriately caution that CD19 testing, disease history, and duration of treatment interruption should inform individualized postpartum reinitiation decisions. The observation that most women restarted on maintenance rather than loading doses without apparent consequence warrants prospective investigation but should not be generalized beyond this small, single-center sample.

Limitations and Future Research

Key limitations include the small sample size (n = 25), single-center design, and relatively short mean postpartum follow-up of 5.9 months. Postpartum CD19 data were unavailable, limiting insight into B-cell recovery kinetics following delivery. Women with early miscarriage or intrapartum DMT switch were excluded, further constraining generalizability.

The absence of a comparator group precluded causal inference. Therefore, larger, multicenter, prospective registries may be needed to characterize B-cell recovery trajectories following ofatumumab discontinuation for pregnancy, validate postpartum reinitiation strategies, and establish whether CD19-guided dosing decisions improve outcomes in this population.

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REFERENCES
1. Bongol D, Antoniou M, Chataway J, et al. B-cell repopulation and postpartum MS disease activity following ofatumumab cessation for pregnancy in women with multiple sclerosis. Mult Scler. Published online July 22, 2026. doi:10.1177/13524585261471448
2. Dobson R, Rog D, Ovadia C, et al. Anti-CD20 therapies in pregnancy and breast feeding: a review and ABN guidelines. Pract Neurol. 2023;23(1):6-14. doi:10.1136/pn-2022-003426
3. Vukusic S, Hutchinson M, Hours M, et al. Pregnancy and multiple sclerosis (the PRIMS study): clinical predictors of post-partum relapse. Brain. 2004;127(Pt 6):1353-1360. doi:10.1093/brain/awh152
4. Abu-Raya B, Michalski C, Sadarangani M, Lavoie PM. Maternal Immunological Adaptation During Normal Pregnancy. Front Immunol. 2020;11:575197. Published 2020 Oct 7. doi:10.3389/fimmu.2020.575197
5. Bast N, Dost-Kovalsky K, Haben S, et al. Anti-CD20 antibodies and pregnancy disease activity in women with multiple sclerosis. Neurology. 2025;104:3588. doi:10.1212/WNL.0000000000211101