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Long-term repopulation of peripheral B-cell subsets after single and repeated rituximab infusions in patients with rheumatoid arthritis
P. Roll1, Z. Mahmood2, K. Muhammad3, M. Feuchtenberger4, T. Dörner5, H.-P. Tony6
- Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
- Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
- Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
- Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
- Charité, Universitätsmedizin Berlin and DRFZ Berlin, Germany.
- Department of Medicine II, Rheumatology and Clinical Immunology, University of Würzburg, Würzburg, Germany.
CER7847
2015 Vol.33, N°3
PI 0347, PF 0353
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PMID: 25897997 [PubMed]
Received: 14/08/2014
Accepted : 19/12/2014
In Press: 16/04/2015
Published: 22/06/2015
Abstract
OBJECTIVES:
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.
CONCLUSIONS:
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.
