title: Influence of FCGR3A genotype on the therapeutic response to rituximab in rheumatoid arthritis: an observational cohort study.
abstract: OBJECTIVE
  To determine whether a polymorphism in the Fcγ receptor type IIIA (FCGR3A-F158V), influencing immunoglobulin G binding affinity, relates to the therapeutic efficacy of rituximab in rheumatoid arthritis (RA) patients.
  
  
  METHODS
  Observational cohort study.
  
  
  METHODS
  Three university hospital rheumatology units in Sweden.
  
  
  METHODS
  Patients with established RA (n=177; 145 females and 32 males) who started rituximab (Mabthera) as part of routine care.
  
  
  METHODS
  Response to rituximab therapy in relation to FCGR3A genotype, including stratification for sex.
  
  
  RESULTS
  The frequency of responders differed significantly across FCGR3A genotypes (p=0.017 in a 3×2 contingency table). Heterozygous patients showed the highest response rate at 83%, as compared with patients carrying 158FF (68%) or 158VV (56%) (p=0.028 and 0.016, respectively). Among 158VV patients, response rates differed between male and female patients (p=0.036), but not among 158FF or 158VF patients (p=0.72 and 0.46, respectively).
  
  
  CONCLUSIONS
  Therapeutic efficacy of rituximab in RA patients is influenced by FCGR3A genotype, with the highest response rates found among heterozygous patients. This may suggest that different rituximab mechanisms of action in RA are optimally balanced in FCGR3A-158VF patients. Similar to the previously described associations with RA susceptibility and disease course, the impact of 158VV on rituximab response may be influenced by sex.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University/ Department of Rheumatology in Östergötland, County Council of Östergötland, Linköping, Sweden.
authors.forename: Alf
authors.initials: A
authors.lastname: Kastbom
authors.forename: Lars
authors.initials: L
authors.lastname: Cöster
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Arlestig
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Chatzidionysiou
authors.forename: Ronald F
authors.initials: RF
authors.lastname: van Vollenhoven
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Solbritt
authors.initials: S
authors.lastname: Rantapää-Dahlqvist
authors.forename: Saedis
authors.initials: S
authors.lastname: Saevarsdottir