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.
Clinic of Rheumathology, Azienda Ospedaliero-Universitaria of Udine, Italy.
Martina
M
Fabris
Luca
L
Quartuccio
Sandra
S
Lombardi
Marta
M
Saracco
Fabiola
F
Atzeni
Antonio
A
Carletto
Marco
M
Cimmino
Cinzia
C
Fabro
Elena
E
Pontarini
Raffaele
R
Pellerito
Lisa Maria
LM
Bambara
Piercarlo
P
Sarzi-Puttini
Maurizio
M
Cutolo
Mariangela
M
Manfredi
Maurizio
M
Benucci
Pia
P
Morassi
Fabio
F
Fischetti
Melissa
M
Padovan
Marcello
M
Govoni
Francesco
F
Curcio
Elio
E
Tonutti
Salvatore
S
De Vita
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