The CC homozygosis of the -174G>C IL-6 polymorphism predicts a lower efficacy of rituximab therapy in rheumatoid arthritis

Martina Fabris, Luca Quartuccio, Sandra Lombardi, Marta Saracco, Fabiola Atzeni, Antonio Carletto, Marco Cimmino, Cinzia Fabro, Elena Pontarini, Raffaele Pellerito, Lisa Maria Bambara, Piercarlo Sarzi-Puttini, Maurizio Cutolo, Mariangela Manfredi, Maurizio Benucci, Pia Morassi, Fabio Fischetti, Melissa Padovan, Marcello Govoni, Francesco CurcioElio Tonutti, Salvatore De Vita

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)315-320
Number of pages6
JournalAutoimmunity Reviews
Issue number5
Publication statusPublished - Mar 2012


  • IL-6
  • Pharmacogenetics
  • Rheumatoid arthritis
  • Rituximab

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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