Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment.
OBJECTIVE
B cell depletion with the anti-CD20 antibody rituximab has proven efficacy in patients with rheumatoid arthritis (RA). The effects on B cell homeostasis after repeated treatments and the relationship of certain B cell subsets to clinical response or relapse are currently not known.


METHODS
In this open-label study, 17 patients with RA refractory to standard therapy were treated with 1 cycle of rituximab. Of these 17 patients, 11 received a second cycle of rituximab therapy. Immunophenotyping was performed before therapy and during B cell recovery.


RESULTS
Twelve of 17 patients showed a good European League Against Rheumatism response after receiving 1 cycle of rituximab therapy. At the time of B cell recovery, the IgD+,CD27+ memory B cell subset was significantly larger (P = 0.019) in the nonresponder group. Within the group of 12 responders, 6 patients, whose disease was characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy, experienced an early relapse (weeks 24-40 posttreatment). Eleven patients were re-treated, again resulting in a good clinical response. B cell reconstitution followed a similar pattern after each cycle. The early reconstitution phase was characterized by immature CD38++,IgD+,CD10+ B cells, whereas the number of naive B cells increased continuously thereafter. The number of memory B cells was still reduced at the time of the second depletion but recovered to levels similar to those following the first cycle of therapy.


CONCLUSIONS
Data derived from repeated B lymphocyte depletion with rituximab in patients with RA suggest that analysis of certain memory B cell subsets provides information on efficacy, response, and late as well as early relapse, consistent with the conclusion that targeting memory B cells is a key to its mechanism of action.
University of Würzburg, Wurzburg, Germany.
Petra
P
Roll
Thomas
T
Dörner
Hans-Peter
HP
Tony
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000145:classification / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D007072:Immunoglobulin D / Q000187:drug effects; D007155:Immunologic Factors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012074:Remission Induction; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D015415:Biomarkers; D007072:Immunoglobulin D; D007155:Immunologic Factors; D000069283:Rituximab