How do B cell depleters work?. Some say because it depletes CD20+, T cells, but affects other T cells as well so it suggests B cells are doing a lot with the immune system. This study looks at ofatumumab and T cell numbers drop with time. The T cell level drops but remains within normal levels with most people. The conclusion is the need to change dosing intervals but the question is based on what logic and which cell type the issue is based.
Tanaka M, Kinoshita M, Tanaka K. T lymphopenia in multiple sclerosis patients treated with ofatumumab: Even with consideration for CD3 + CD20+ cells. Mult Scler J Exp Transl Clin. 2026; 12: 20552173251409954. doi: 10.1177/20552173251409954.
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 the NTZ-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.
Source: multiple-sclerosis-research.org