B lymphocyte-typing for prediction of clinical response to rituximab

Arthritis Res Ther. 2012 Jul 6;14(4):R161. doi: 10.1186/ar3901.

Abstract

Introduction: The prediction of therapeutic response to rituximab in rheumatoid arthritis is desirable. We evaluated whether analysis of B lymphocyte subsets by flow cytometry would be useful to identify non-responders to rituximab ahead of time.

Methods: Fifty-two patients with active rheumatoid arthritis despite therapy with TNF-inhibitors were included in the national rituximab registry. DAS28 was determined before and 24 weeks after rituximab application. B cell subsets were analyzed by high-sensitive flow cytometry before and 2 weeks after rituximab administration. Complete depletion of B cells was defined as CD19-values below 0.0001 x10⁹ cells/liter.

Results: At 6 months 19 patients had a good (37%), 23 a moderate (44%) and 10 (19%) had no EULAR-response. The extent of B lymphocyte depletion in peripheral blood did not predict the success of rituximab therapy. Incomplete depletion was found at almost the same frequency in EULAR responders and non-responders. In comparison to healthy controls, non-responders had elevated baseline CD95⁺ pre-switch B cells, whereas responders had a lower frequency of plasmablasts.

Conclusions: The baseline enumeration of B lymphocyte subsets is still of limited clinical value for the prediction of response to anti-CD20 therapy. However, differences at the level of CD95⁺ pre switch B cells or plasmablasts were noticed with regard to treatment response. The criterion of complete depletion of peripheral B cells after rituximab administration did not predict the success of this therapy in rheumatoid arthritis.

MeSH terms

  • Antibodies, Monoclonal, Murine-Derived / pharmacology
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / metabolism*
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Registries
  • Rituximab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • Rituximab