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AB0538 TNFAIP3 RS675520 variant may predict response to rituximab treatment in rheumatoid arthritis
  1. I. Guseva1,
  2. N. Soroka2,
  3. A. Devyataykina3,
  4. G. Lukina3,
  5. E. Aleksandrova4,
  6. A. Novikov4,
  7. S. Glukhova5,
  8. D. Trofimov2,
  9. E. Nasonov6
  1. 1Laboratory of Genetics, Institute of Rheumatology
  2. 2Laboratory of Immunogenetics, NRC Institute of Immunology of FMBA of Russia
  3. 3Laboratory of Clinical Pharmacology
  4. 4Laboratory of Clinical Immmunology and Molecular Biology
  5. 5Laboratory of Information Technologies
  6. 6Department of Vascular Pathology, Institute of Rheumatology, Moscow, Russian Federation

Abstract

Background Individual response to biological treatment is highly variable and potentially subject to genetics influence. There is a need for biomarkers that are able to predict clinical response to rituximab (RTX) treatment.

Objectives To examine whether there are genetic polymorphisms associated with response to RTX therapy.

Methods 53 RA patients receiving RTX therapy were included in this pharmacogenetic prospective study (mean age 51±15 years and mean disease duration 8.2±6.2 years). Response to RTX therapy was evaluated using the EULAR criteria (DAS28-ESR) at 6 months after the first RTX course (two intravenous infusions at weeks 0 and 2). The following gene polymorphisms (SNPs) were genotyped: IL-6 (rs1800795), IL-6RA (rs8192284), TNFA (rs1800629), TNFAIP3 (rs675520, rs6920220, rs10499194), MCP-1/CCL2 (rs1024611), CTLA4 (rs3087243), PTPN22 (rs2476601). Comparison of responses for the following groups (good responders vs moderate/non responders, and good responders vs moderate responders) was evaluated using logistic regression, and the results were expressed as ORs with 95% CI.

Results After the 1st RTX course a good response was achieved in 18 (40,0%) patients. 29 (54,7%) patients were defined as moderate responders and 6 (11,3%) patients as non-responders. A SNP at TNFAIP3 locus (rs675520) tended to be associated with the response to RTX treatment in both groups of responders vs moderate/non responders (OR 4,6, 95% CI 0,9-23,6, p=0,06) and responders vs moderate responders (OR 4,8, 95% CI 0,9-25,5, p=0,062). The patients with homozygous genotype CC had the worse results than patients with CT and TT genotypes in the swollen joint count (p=0,036), tender joint count (p=0,034), DAS28 (p=0,01) and HAQ (p=0,01) at 6 months after the first course of treatment. No evidence for association was detected at the other SNPs tested

Conclusions Our preliminary results suggest the TNFAIP3 SNP (rs675520) may possibly influence the response to RTX therapy. This finding requires replication in additional patients groups.

Disclosure of Interest None Declared

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