Influence of FCGR3A genotype on the therapeutic response to rituximab in rheumatoid arthritis: An observational cohort study

Objectives: 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. Design: Observational cohort study. Setting: Three university hospital rheumatology units in Sweden. Participants: Patients with established RA (n=177; 145 females and 32 males) who started rituximab (Mabthera) as part of routine care. Primary outcome measures: 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 3x2 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.