T lymphopenia in multiple sclerosis patients treated with ofatumumab - Even with consideration for CD3 + CD20 + cells

Sep 28, 2026

Background: B cell depleting therapy is a cornerstone for relapsing-remitting multiple sclerosis, and ofatumumab (OFA) was expected to cause fewer adverse events given lower maximum blood concentration than ocrelizumab. Methods: 38 RRMS patients receiving at least 5 months of standard OFA underwent CD3+CD20+ cell-count assessment before treatment. Results: CD3+CD20+ cells rose up to 75/μL, with higher levels in the natalizumab-to-OFA group; Grade 2 lymphopenia occurred in 7/33. Conclusion: Beyond B-cell depletion, a broader-than-expected T-cell reduction lacking CD20 was observed, suggesting interval adjustments for long-term therapy.

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Original research article T lymphopenia in multiple sclerosis patients treated with ofatumumab: Even with consideration for CD3 + CD20 + cells Masami Tanaka , Masako Kinoshita and Keiko Tanaka Abstract Background: B cell depleting therapy has become a cornerstone in disease-modifying treatments for relapsing-remitting multiple sclerosis (RRMS) . Given that the maximum blood concentration of ofatumumab (OFA) is two orders of magnitude lower than that of ocrelizumab, it was anticipated that OFA would result in fewer adverse events. Methods: The study included 38 RRMS patients had received at least 5 months of standard OFA administration. CD3 + CD20+ cell counts were assessed prior to OFA administration. Results: The number of CD3 + CD20+ cells reached up to 75/μL in the treatment groups other than NTZ, and up to 200/μL in theNTZ-treated group, where B cell levels increased. Lymphopenia classiﬁes as Grade 2 (800/μL or less) was observed in 7/33 cases. Beyond the depletion of CD3 + CD20+ cells, a reduction in CD3+ cells was noted in 29 of 33 cases (88%), and with seven cases showing progressive T cell decline for up to 5 months after OFA initiation. Conclusion: In addition to the expected depletion of B cells, there was a greater-than-anticipated reduction in T cells lacking CD20 expression. Long-term continuous BCDT appears to have a profound impact on the immune system. Adjustments to administration intervals should be considered to mitigate the risk of over-treatment. Keywords: multiple sclerosis, ofatumumab, ﬁngolimod, CD3+ CD20+ cells, T-cell lymphopenia Date received: 17 June 2025; accepted 7 December 2025 Highlights: • Analysis of 38 RRMS patients treated with ofatumumab for 5 months. • CD3 + CD20+ cells reached up to 200/μL innatalizumab-treated patients. • Grade 2 lymphopenia (≤800/μL) observed in 21% . • CD3 + cell reduction occurred in 88%, with 7 cases showing progressive T cell decline over 5 months. Introduction Although the exact pathomechanisms of multiple sclerosis (MS) is unknown, genome-wide association studies have shown that genes related to the activation and proliferation of helper T cells are involved in the risk of developing the disease, and it is thought to becaused by T cell-mediated autoimmune mechanisms.1 Baker et al. showed that drugs that reduce memory B cells in the peripheral blood were effective in clinical trials in patients with MS. Conversely, clinical trials were stopped halfway through for drugs that increased them, such as atacicept, because MS disease activity increased, suggesting the effectiveness of B-cell depletion therapy (BCDT).2 Furthermore, clinical trials of ocrelizumab (OCR) for Relapsing-remitting MS (RRMS)3 and Primary progressive MS (PPMS)4 have shown positive results in terms of clinical symptoms and brain MRI ﬁndings. It was reported that subcutaneous injections of ofatumumab (OFA), which are easier to administer, signiﬁcantly reduced disease activity compared to teriﬂunomide.5 Multiple Sclerosis Journal—Experimental, Translational and Clinical January–March 2026, 1–14 DOI: 10.1177/ 20552173251409954 © The Author(s), 2026 . Article reuse guidelines: [sagepub.com/journals](sagepub.com/journals)permissions Correspondence to: Masami Tanaka, Kyoto MS Center, Kyoto Min-Iren Chuo Hospital, Kyoto, Japan; Department of Neurology, Kaikokai Josai Hospital, Nagoya, Japan. [95masa17777@gmail.com](95masa17777@gmail.com) Masami Tanaka, Kyoto MS Center, Kyoto Min-Iren Chuo Hospital, Kyoto, Japan Department of Neurology, Kaikokai Josai Hospital, Nagoya, Japan Masako Kinoshita, Department of Neurology, Utano National Hospital, Kyoto, Japan Keiko Tanaka, Department of Multiple Sclerosis Therapeutics, Fukushima Medical Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecom

FAQs

What is the main background rationale for using ofatumumab in RRMS patients?

The study frames OFA as a B cell depleting therapy for RRMS and notes that its maximum blood concentration is much lower than that of ocrelizumab, suggesting fewer adverse events.

How was the study conducted and which cells were assessed?

Thirty-eight RRMS patients treated with OFA for at least 5 months were included, with CD3+CD20+ cell counts assessed prior to OFA administration.

What were the key findings regarding lymphopenia and T cells after OFA?

Grade 2 lymphopenia was observed in 7/33 cases. After CD3+CD20+ depletion, CD3+ cell reduction occurred in 29/33 cases, and seven cases showed progressive T-cell decline up to 5 months after starting OFA.

Sep 28, 2026

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