title: The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: results of an Italian multicentre study.
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.
authors.affiliation: Department of Medical and Biological Sciences, Clinic of Rheumatology, University of Udine, , Udine, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Quartuccio
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Elena
authors.initials: E
authors.lastname: Pontarini
authors.forename: Sara
authors.initials: S
authors.lastname: Salvin
authors.forename: Alen
authors.initials: A
authors.lastname: Zabotti
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manfredi
authors.forename: Domenico
authors.initials: D
authors.lastname: Biasi
authors.forename: Viviana
authors.initials: V
authors.lastname: Ravagnani
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
authors.forename: Pia
authors.initials: P
authors.lastname: Morassi
authors.forename: Fabio
authors.initials: F
authors.lastname: Fischetti
authors.forename: Paola
authors.initials: P
authors.lastname: Tomietto
authors.forename: Laura
authors.initials: L
authors.lastname: Bazzichi
authors.forename: Marta
authors.initials: M
authors.lastname: Saracco
authors.forename: Raffaele
authors.initials: R
authors.lastname: Pellerito
authors.forename: Marco
authors.initials: M
authors.lastname: Cimmino
authors.forename: Franco
authors.initials: F
authors.lastname: Schiavon
authors.forename: Valeria
authors.initials: V
authors.lastname: Carraro
authors.forename: Angelo
authors.initials: A
authors.lastname: Semeraro
authors.forename: Roberto
authors.initials: R
authors.lastname: Caporali
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cavagna
authors.forename: Roberto
authors.initials: R
authors.lastname: Bortolotti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolazzi
authors.forename: Marcello
authors.initials: M
authors.lastname: Govoni
authors.forename: Stefano
authors.initials: S
authors.lastname: Bombardieri
authors.forename: Salvatore
authors.initials: S
authors.lastname: De Vita
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis; D017452:Receptors, IgG / Q000235:genetics*; D012189:Retrospective Studies; D000069283:Rituximab; D017422:Sequence Analysis, DNA / Q000379:methods; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D015415:Biomarkers; C496124:FCGR3A protein, human; D017452:Receptors, IgG; D000069283:Rituximab
keywords: Pharmacogenetics; Rheumatoid Arthritis; Rheumatoid Factor