The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis.
Identification of genetic biomarkers of response to biologics in rheumatoid arthritis (RA) is a relevant issue. Being IL-6 a key cytokine for B cell survival, the interleukin-6 (IL-6) -174G>C and the IL-6 receptor (IL-6R) D358A gene polymorphisms were investigated in 158 RA patients treated with rituximab (RTX). One hundred and twenty-eight (81.0%) were RF positive and 126 (79.7%) were anti-CCP positive. Response to therapy was evaluated at the end of the sixth month after the first RTX infusion, by using both the EULAR and the ACR criteria. The possible relationship with IL-6 serum levels was also studied. By univariate analysis, lack of response by the EULAR criteria was more prevalent in RA patients with the IL-6 -174 CC genotypes (39.1%), than in the GC/GG patients (18.5%) (OR 2.83; 95%CI=1.10-7.27; p=0.031). A good response was noticed in only one patient (4.3%) with the IL-6 -174 CC genotype, while it was present in 24.4% of GG/GC cases (p=0.06). By stepwise multivariate analysis (including RA duration, baseline DAS28, baseline HAQ, RF status, anti-CCP status and IL-6 genotype as covariates), the IL-6 -174CC genotype was selected as an independent predictor of no response to RTX by both EULAR and ACR≥50 criteria, while the IL-6R polymorphism resulted as not associated. No definite association between gene polymorphisms and IL-6 serum levels was noticed. Present results suggest a possible role for IL-6 genotyping to better plan treatment with RTX in RA, and larger studies are worthwhile.
Fabris
Martina
M
Clinic of Rheumathology, Azienda Ospedaliero-Universitaria of Udine, Italy.
Quartuccio
Luca
L
Lombardi
Sandra
S
Saracco
Marta
M
Atzeni
Fabiola
F
Carletto
Antonio
A
Cimmino
Marco
M
Fabro
Cinzia
C
Pontarini
Elena
E
Pellerito
Raffaele
R
Bambara
Lisa Maria
LM
Sarzi-Puttini
Piercarlo
P
Cutolo
Maurizio
M
Manfredi
Mariangela
M
Benucci
Maurizio
M
Morassi
Pia
P
Fischetti
Fabio
F
Padovan
Melissa
M
Govoni
Marcello
M
Curcio
Francesco
F
Tonutti
Elio
E
De Vita
Salvatore
S
D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D003062:Codon; D005260:Female; D006720:Homozygote; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D019947:Receptors, Interleukin-6 / Q000235:genetics; D000069283:Rituximab; D016896:Treatment Outcome
D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D003062:Codon; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D000069283:Rituximab