A group of scientists report that memory B cells play a key role in the compromised immune reaction of rheumatoid arthritis (RA) patients and the short-term gains of rituximab therapy. The researchers found a significant correlation between the size of the IgD+, CD27+ memory B-cell subset during the arly phase of B-cell repletion and the response to anti-CD20 treatment.
“Patients with lower numbers of IgD memory cells at the beginning of peripheral B-cell repopulation had a much more favorable clinical response,” notes Hans-Peter Tony, M.D., at the University of Wurzburg. “Therefore, the extent of memory B-cell repletion seems to be a key factor influencing the pathophysiology of RA.”
Anti-CD20 antibody rituximab acts by depleting B cells. In the majority of responders, though, the disease relapses over time, the researchers point out. They thus decided to identify predictors of response or relapse to rituximab.
The evaluation began with an open-label trial of one cycle of rituximab on 17 RA patients. The participants, 14 women and three men, had a median age of 51 years and a median disease duration of 14 years. Of these patients, 16 received two infusions rituximab, 1,000 milligrams each, two weeks apart, and one patient received four weekly infusions of rituximab at a dose of 375 milligrams. Blood samples from all participants were obtained at baseline, on day 15, and at a three-month follow-up, and analyzed for B-cell repopulation.
After receiving one cycle of rituximab, 12 of the 17 patients showed a good clinical response, with significant improvement in the Disease Activity Score in 28 joints (DAS28). At the time of B-cell recovery, the IgD+, CD27+ memory B-cell subset was significantly larger in the nonresponder group. Within the group of 12 responders, six patients experienced an early relapse of RA activity, between 24 and 40 weeks after rituximab treatment. The relapsers were characterized by a significantly higher proportion of overall CD27+ memory B cells before therapy.
Then 11 patients were retreated and again achieved a good clinical response. After the second cycle of rituximab, the pattern of B-cell reconstitution was repeated. The number of B cells was still reduced at the time of second depletion but recovered to levels similar to those following the first cycle of therapy. This indicates an unimpaired capacity of B-cell regeneration after repeated B-cell depletion, the investigators explain.
The research group reports that further work is required into whether patients with a high level of particular memory B cells may benefit from early retreatment or may even require higher doses of this anti-CD20 antibody.
The study was conducted by Dr. Tony and Petra Roll, M.D., from the University of Wurzburg, and Thomas Drner, M.D., affiliated with the University of Berlin. Their analysis appears in the June issue of Arthritis & Rheumatism.