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FRI0255 The 158vv fcgamma receptor 3a genotype is associated with response to rituximab in rheumatoid arthritis: results of an italian multicentre study
  1. L. Quartuccio1,
  2. M. Fabris2,
  3. E. Pontarini3,
  4. S. Salvin3,
  5. A. Zabotti3,
  6. M. Benucci4,
  7. M. Manfredi4,
  8. D. Biasi5,
  9. V. Ravagnani5,
  10. F. Atzeni6,
  11. P. Sarzi Puttini6,
  12. P. Morassi7,
  13. F. Fischetti7,
  14. P. Tomietto7,
  15. L. Bazzichi8,
  16. M. Saracco9,
  17. R. Pellerito9,
  18. M. Cimmino10,
  19. F. Schiavon11,
  20. V. Carraro11,
  21. A. Semeraro12,
  22. R. Caporali13,
  23. L. Cavagna13,
  24. R. Bortolotti14,
  25. G. Paolazzi14,
  26. M. Govoni15,
  27. S. Bombardieri8,
  28. S. De Vita1
  1. 1Department of Biological and Medical Sciences, Rheumatology Clinic, University Hospital of Udine
  2. 2Institute of Clinical Pathology, University Hospital of Udine
  3. 3Rheumatology Clinic, University Hospital of Udine, UDINE
  4. 4Unit of Rheumatology, Ospedale San Giovanni di Dio, Florence
  5. 5Rheumatology Clinic, University of Verona, Verona
  6. 6Clinic of Rheumatology, Ospedale L. Sacco, Milan
  7. 7Internal Medicine, Ospedali Riuniti of Trieste, Trieste
  8. 8Rheumatology Unit, University of Pisa, Pisa
  9. 9Unit of Rheumatology, Ospedale Mauriziano, Turin
  10. 10Clinic of Rheumatology, University of Genova, Genova
  11. 11Rheumatology Clinic, University of Padova, Padova
  12. 12Unit of Rheumatology, Ospedale Valle d’Itria, Martina Franca (TA)
  13. 13Unit of Rheumatology, Ospedale S. Matteo, Pavia, Italy, Pavia
  14. 14Unit of Rheumatology, Santa Chiara Hospital, Trento
  15. 15Clinic of Rheumatology, Azienda Ospedaliero-Universitaria of Ferrara, Ferrara, Italy

Abstract

Background Receptors for IgG allow antibody-dependent cell cytotoxicity, and the polymorphism 158V/F (rs396991) of the Fc fragment of IgG type 3A (FCG3A) was investigated as a genetic factor influencing disease response after rituximab (RTX) therapy in haematologic and rheumatic diseases.

Objectives The aim of this study was to better evaluate of the association between 158V/F FCGR3A polymorphism and response to RTX, by analysing a larger series of patients and by dissecting the results at month +4 and at month +6 after treatment. The pharmacogenetic data were also integrated with established clinical predictors of response to RTX in RA, i.e., rheumatoid factor (RF) and/or anti-cyclic citrullinated peptides (anti-CCP) antibodies, baseline DAS28, baseline HAQ, number of TNF blockers previously failed.

Methods The study analysed 212 RA patients. Patients were referred to 13 different rheumatologic Centres in Italy. They were unselected and represented the majority of the RA subjects treated with RTX in any single participating centre. Patients were followed for at least 6 months after RTX treatment, from 2004 to 2011, and data were collected after the first cycle of RTX. EULAR response was evaluated at months +4 and +6 after the first RTX infusion. The FCGR3A polymorphism was analysed by PCR followed by Sanger sequencing.

Results The FCGR3A genotypes were associated with EULAR response (good or moderate) at month +6 [response in 34/38 (89.5%) VV vs. 70/106 (66%) VF and in 51/77 (66.2%) FF patients; p=0.01], but not at month +4 [response in 32/37 (86.5%) VV vs. 69/102 (67.6%) VF and 53/73 (72.6%) FF patients; p=0.09]. Loss of response was observed only in VF and FF carriers [(VV vs VF vs FF: 0/37 (0%) vs 11/102 (10.8%) vs 12/73 (16.4%); p=0.02)]. Probability of response at month +6 was very high when at least two of the three following items selected by multivariate analysis were present: positive rheumatoid factor and/or anti-CCP antibodies, previous treatment with ≤1 anti-TNF agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95%CI 4.1-15.1).

Conclusions The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Previous results from a similar French study (1) were partially confirmed in an Italian population. Patient genotyping may be helpful to plan RTX treatment, and, notably, may be integrated with clinical predictors.

References

  1. Ruyssen-Witrand A, et al. FcY receptor type IIIA polymorphism influences treatment outcomes in patients with rheumatoid arthritis treated with rituximab. Ann Rheum Dis. 2012;71:875-7

Disclosure of Interest: None Declared

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