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Combination of B cell biomarkers as independent predictors of response in patients with rheumatoid arthritis treated with rituximab

1, 2, 3, 4, 5, 6, 7

 

  1. Department of Rheumatology and Immunology, University of Würzburg, Germany. tony_h@medizin.uni-wuerzburg.de
  2. Department of Rheumatology and Immunology, University of Würzburg, Germany.
  3. Hospital for Rheumatology and Clinical Immunology Berlin, and DRFZ, Berlin, Germany.
  4. Ecron Acunova GmbH, Frankfurt, Germany.
  5. Ecron Acunova GmbH, Frankfurt, Germany.
  6. Roche Pharma AG, Grenzach-Wyhlen, Germany.
  7. Hospital for Rheumatology and Clinical Immunology Berlin, and DRFZ, Berlin, Germany.

on behalf of the FIRST/ ReFIRST study teams

CER8117
2015 Vol.33, N°6
PI 0887, PF 0894
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PMID: 26517829 [PubMed]

Received: 14/11/2014
Accepted : 27/07/2015
In Press: 30/10/2015
Published: 15/12/2015

Abstract

OBJECTIVES:
Identification of B cell biomarkers predictive of response prior to therapy with rituximab (RTX) and evaluation of the efficacy of long-term treatment in patients with rheumatoid arthritis (RA).
METHODS:
302 RA patients failing one TNFi were treated with two applications of 1000 mg RTX (FIRST study). During the follow-up study (ReFIRST) the patients were treated for up to three more courses if they showed measurable clinical response but RA was still active. In a substudy on 154 RA patients peripheral B cell subsets were determined by flow cytometry before starting RTX. Rheumatoid factor (RF), RF-isotypes and anti-citrullinated protein antibodies (ACPA) were also measured.
RESULTS:
Based on multivariate analyses patients with positive RF and normal (>lower limit) levels of CD19+ B cells (RF+/CD19+) showed better treatment effects compared to patients who had only one or none of those parameters. Considering the RF status of the patients, analysis of B cell subpopulations yielded a correlation between higher ER rates and “double negative” CD19+CD27-IgD- B cells. Lowest ER rates were observed for RF negative patients in combination with low numbers of CD19+CD27-IgD- B cells as independent risk factors, thus defining a group with lower responses. Conversely, higher CD19+CD27-IgD- B cells identified a responder group within RF negative patients.
CONCLUSIONS:
The data of this large biomarker study suggest that beyond RF positivity, normal levels of CD19+ B cells together with increased CD19+CD27-IgD- B cells predict response to RTX in RA, in particular when all parameters were present.

Rheumatology Article