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The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: results of an Italian multicentre study
  1. Luca Quartuccio1,
  2. Martina Fabris1,2,
  3. Elena Pontarini1,
  4. Sara Salvin1,
  5. Alen Zabotti1,
  6. Maurizio Benucci3,
  7. Mariangela Manfredi3,
  8. Domenico Biasi4,
  9. Viviana Ravagnani4,
  10. Fabiola Atzeni5,
  11. Piercarlo Sarzi-Puttini5,
  12. Pia Morassi6,
  13. Fabio Fischetti6,
  14. Paola Tomietto6,
  15. Laura Bazzichi7,
  16. Marta Saracco8,
  17. Raffaele Pellerito8,
  18. Marco Cimmino9,
  19. Franco Schiavon10,
  20. Valeria Carraro10,
  21. Angelo Semeraro11,
  22. Roberto Caporali12,
  23. Lorenzo Cavagna12,
  24. Roberto Bortolotti13,
  25. Giuseppe Paolazzi13,
  26. Marcello Govoni14,
  27. Stefano Bombardieri7,
  28. Salvatore De Vita1
  1. 1Department of Medical and Biological Sciences, Clinic of Rheumatology, University of Udine, Udine, Italy
  2. 2Institute of Clinical Pathology, Azienda Ospedaliero-Universitaria of Udine, Udine, Italy
  3. 3Unit of Rheumatology, Ospedale San Giovanni di Dio, Firenze, Italy
  4. 4Clinic of Rheumatology, University of Verona, Verona, Italy
  5. 5Rheumatology Unit, Ospedale L. Sacco, Milano, Italy
  6. 6Clinic of Internal Medicine, Ospedali Riuniti of Trieste, Trieste, Italy
  7. 7Clinic of Rheumatology, University of Pisa, Pisa, Italy
  8. 8Unit of Rheumatology, Ospedale Mauriziano, Torino, Italy
  9. 9Clinic of Rheumatology, University of Genova, Genova, Italy
  10. 10Clinic of Rheumatology, University of Padova, Padova, Italy
  11. 11Unit of Rheumatology, Ospedale Valle d'Itria, Martina Franca (TA), Italy
  12. 12Clinic of Rheumatology, Ospedale S. Matteo, Pavia, Italy
  13. 13Unit of Rheumatology, Santa Chiara Hospital, Trento, Italy
  14. 14Clinic of Rheumatology, Azienda Ospedaliero-Universitaria of Ferrara, Ferrara, Italy
  1. Correspondence to Dr Salvatore De Vita, Department of Medical and Biological Sciences, Rheumatology Clinic, University Hospital ‘Santa Maria della Misericordia’, Udine 33100, Italy; devita.salvatore{at}aoud.sanita.fvg.it

Abstract

Objective The polymorphism 158V/F of Fc fragment of IgG (FCGR) type 3A may influence the response to rituximab (RTX) in rheumatoid arthritis (RA). We investigated the FCG3A polymorphism in a large cohort of RA patients treated with RTX, also by considering the possible loss of response from month +4 to +6 after RTX and the presence of established predictors of response.

Methods The study analysed 212 RA patients. European League Against Rheumatism (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 anticyclic citrullinated peptide antibodies, previous treatment with ≤1 anti-tumor necrosis factor (TNF) agent, and 158VV FCGR3A genotype (p<0.0001; OR 7.9, 95% CI 4.1 to 15.1).

Conclusions The 158VV FCGR3A genotype was associated with response to RTX in a large cohort of RA patients. Patient genotyping may be helpful to plan RTX treatment, and may be integrated with clinical predictors.

  • Rheumatoid Arthritis
  • Rheumatoid Factor
  • Pharmacogenetics

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