The 158VV Fcgamma receptor 3A genotype is associated with response to rituximab in rheumatoid arthritis: Results of an italian multicentre study

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