Long-term repopulation of peripheral B-cell subsets after single and repeated rituximab infusions in patients with rheumatoid arthritis

Objective: B-cell depletion using rituximab (RTX) has proven efficacy in patients with RA. Long-term effects on the B-cell system after single and repeated treatments are sparse. Our aim was to study the effect of multiple courses of rituximab to evaluate its impact on repeated B-cell re-population capacity. Methods: Two cohorts, altogether 20 patients with RA were included in an open label extension study with RTX. Cohort 1 received one cycle RTX and was followed for up to 7 years. In cohort 2 patients were studied under up to 5 cycles of RTX. Immunophenotyping was performed before therapy and during follow-up. Results: After a single therapy with RTX (cohort 1) the frequency of pre-switch (MZ-like) B cells were significantly reduced during the follow-up of 7 years and absolute numbers slowly repopulated to nearly 50% of baseline value without numerical normalisation. The acquisition of mutations in Ig receptors of pre-switch (MZ-like) memory B cells was also significantly reduced 10 years after one course. In contrast, absolute numbers of (classical) post-switch B cells tended to normalise to baseline values after 7 years. Analysing B-cell repopulation capacities after multiple cycles revealed (cohort 2) a comparable repopulation pattern after each cycle with no substantial further impact on memory B cells. Conclusion: A single therapy with RTX leads to long-term changes in the memory B-cell compartment particularly in pre-switch memory B cells. Multiple cycles of RTX show a comparable repopulation pattern after each cycle with no additional cumulative effect on memory B cells.