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A1.73 Relationship between expression of synovial B cell survival factors and clinical response to rituximab treatment in rheumatoid arthritis
  1. Rogier M Thurlings1,
  2. Marie Boumans1,
  3. W J de Jager3,
  4. Koen Vos1,2,
  5. Daisy Marie van Westing1,
  6. Lisa G van Baarsen1,
  7. Danielle M Gerlag1,
  8. B Prakken3,
  9. Paul P Tak1,
  10. Paul P Tak4
  1. 1Division of Clinical Immunology and Rheumatology, Academic Medical Center/ University of Amsterdam, Amsterdam, The Netherlands
  2. 2Department of Rheumatology, Flevoziekenhuis, Almere, The Netherlands
  3. 3Department of Pediatric Rheumatology, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
  4. 4Glaxo Smith Kline, Stevenage, UK

Abstract

Background and Objectives Rituximab aims to deplete CD20 positive B cells and exerts a significant and often long-lasting clinical effect in a subset of patients with rheumatoid arthritis (RA). The extent of B cell depletion in the inflammatory tissues after rituximab varies between patients and persistence of plasma cells and plasma cell products is associated with clinical non-response. This suggests rituximab may fail to deplete pathogenic B cells. We investigated whether this might be explained by differential expression of B cell survival factors in the inflamed synovial tissue of RA patients.

Material and Methods Twenty-four RA patients underwent an arthroscopic synovial biopsy before, 1 month after and 4 months after treatment with rituximab. Treatment was given via two infusions (1,000 mg on day 1 and 15), both without methylprednisolon premedication to be able to study specific biological effects of rituximab. Clinical response was defined as a response according to the European League Against Rheumatism (EULAR) criteria at week 24. Peripheral blood and synovial tissue were analysed for expression and levels of B cell survival factors; BLyS, APRIL, IL-1β, IL6, BLyS, VCAM, ICAM, IFNα, CXCL12 and BLIMP1. Correlation between baseline expression and changes in B cell survival factors and clinical response were calculated using logistic regression analysis.

Results We found no significant correlation between baseline expression level of synovial B cell survival factors and clinical response to treatment. After treatment, the expression levels of BLyS, APRIL, IL-1β, IL6, ICAM and BLIMP1 were unaltered. The expression of IFNα and VCAM decreased after treatment, of which VCAM within one month (P = 0.035, P = 0.022 and P = 0.039, respectively). In contrast, expression of CXCL-12 increased after treatment (P = 0.046). In clinical responders VCAM expression decreased further between 1 and 4 months after treatment, although a statistical significant difference with non-responders could not be detected.

Conclusions Clinical non-response to rituximab is not associated with a higher baseline expression of B cell survival factors in the inflamed synovial tissue of RA patients. However, the persistent expression of survival factors independent of the extent of B cell depletion may promote the persistence of pathogenic B cell subsets in clinical non-responders to treatment.

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