Anti-CD20 therapy in patients with rheumatoid arthritis: predictors of response and B cell subset regeneration after repeated treatment.

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.
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.
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.
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.
AuthorsPetra Roll, Thomas Dörner, Hans-Peter Tony
JournalArthritis and rheumatism (Arthritis Rheum) Vol. 58 Issue 6 Pg. 1566-75 (Jun 2008) ISSN: 0004-3591 [Print] United States
PMID18512772 (Publication Type: Clinical Trial, Journal Article)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20
  • Biomarkers
  • Immunoglobulin D
  • Immunologic Factors
  • Rituximab
  • Adult
  • Aged
  • Antibodies, Monoclonal (therapeutic use)
  • Antibodies, Monoclonal, Murine-Derived
  • Antigens, CD20 (immunology)
  • Arthritis, Rheumatoid (drug therapy, immunology)
  • B-Lymphocyte Subsets (classification, drug effects)
  • Biomarkers (blood)
  • Female
  • Humans
  • Immunoglobulin D (drug effects)
  • Immunologic Factors (therapeutic use)
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Rituximab

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password:
Type Validation Code Shown: