Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 315-320 |
| Number of pages | 6 |
| Journal | Autoimmunity Reviews |
| Volume | 11 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Mar 2012 |
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Keywords
- IL-6
- Pharmacogenetics
- Rheumatoid arthritis
- Rituximab
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis. / Fabris, Martina; Quartuccio, Luca; Lombardi, Sandra; Saracco, Marta; Atzeni, Fabiola; Carletto, Antonio; Cimmino, Marco; Fabro, Cinzia; Pontarini, Elena; Pellerito, Raffaele; Bambara, Lisa Maria; Sarzi-Puttini, Piercarlo; Cutolo, Maurizio; Manfredi, Mariangela; Benucci, Maurizio; Morassi, Pia; Fischetti, Fabio; Padovan, Melissa; Govoni, Marcello; Curcio, Francesco; Tonutti, Elio; De Vita, Salvatore.
In: Autoimmunity Reviews, Vol. 11, No. 5, 03.2012, p. 315-320.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis
AU - Fabris, Martina
AU - Quartuccio, Luca
AU - Lombardi, Sandra
AU - Saracco, Marta
AU - Atzeni, Fabiola
AU - Carletto, Antonio
AU - Cimmino, Marco
AU - Fabro, Cinzia
AU - Pontarini, Elena
AU - Pellerito, Raffaele
AU - Bambara, Lisa Maria
AU - Sarzi-Puttini, Piercarlo
AU - Cutolo, Maurizio
AU - Manfredi, Mariangela
AU - Benucci, Maurizio
AU - Morassi, Pia
AU - Fischetti, Fabio
AU - Padovan, Melissa
AU - Govoni, Marcello
AU - Curcio, Francesco
AU - Tonutti, Elio
AU - De Vita, Salvatore
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - IL-6
KW - Pharmacogenetics
KW - Rheumatoid arthritis
KW - Rituximab
UR - http://www.scopus.com/inward/record.url?scp=84857501180&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857501180&partnerID=8YFLogxK
U2 - 10.1016/j.autrev.2010.06.012
DO - 10.1016/j.autrev.2010.06.012
M3 - Article
C2 - 20974296
AN - SCOPUS:84857501180
VL - 11
SP - 315
EP - 320
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
SN - 1568-9972
IS - 5
ER -