Article Text

PDF
CP-084 Interleukin-6–174G>C genetic polymorphism (RS1800795) and the influence of clinical variables on the response to TOCILIZUMAB
  1. X Díaz-Villamarín,
  2. CL Dávila-Fajardo,
  3. D Blánquez-Martínez,
  4. A Caballero-Romero,
  5. A Rodríguez-Delgado,
  6. M González-Medina
  1. Pharmacy Unit-Granada Hospital, Pharmacy, Granada, Spain

Abstract

Background Interleukin 6(IL-6) is involved in the pathogenesis of rheumatoid arthritis via its broad effects on immune and inflammatory responses. Sustained IL-6 activity can cause tissue damage in different tissues. Previous studies have shown that G allele at the IL-6-174G>C (rs1800795) polymorphism is related to high producing IL-6. Other clinical variables such as being treated with methotrexate or DAS28 at baseline have been associated with interindividual differences in the response to tocilizumab.

Purpose The aim of this study was to evaluate the influence of the IL-6-174G>C (rs1800795) polymorphism and other clinical variables on the response to tocilizumab at 3 months after the first dose of the drug.

Material and methods The IL-6-174G>C polymorphism was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 3 months after the first dose of the drug using the 28 joint disease activity score criteria (DAS28). Patients were classified as ‘responders’ (good or moderate response according to EULAR criteria) or ‘non-responders’ (poor response according to EULAR criteria). EULAR good response is defined as a change in DAS28 >1.2 and DAS28 ≤3.2; EULAR moderate response is defined as a change in DAS28 of 0.6–1.2 and DAS28 ≤5.1, or a change of DAS28 >1.2 and DAS28 >3.2.

Results Clinical data from 127 patients were obtained; from all the variables included, we found statistical significance (p<0.05) for the association between the IL-6-174 C/C genotype with non-responders (OR 2.99; 95% CI 1.07–8.34, p=0.039) and for having concomitant methotrexate with ‘responders’ (OR 5.96; 95% CI 1.49–34.82; p=0.004). We did not found significant associations between response and the following variables: age (p=0.71), sex (p=0.22), weight (p=0.39), height (p=0.11), body mass index (p=0.99), baseline DAS28 (p=0.65), positive rheumatoid factor (0.86), erosions (p=0.17); previous treatment with infliximab (p=0.89), etanercept (p=0.52), adalimumab (p=0.93), rituximab (p=0.57), abatacept (p=0.27), certolizumab (p=0.41) or golimumab (p=0.60); and other concomitant treatments(corticosteroids (p=0.48), leflunomide (p=0.22) and sulfasalazine (p=0.25)).

Conclusion Our data confirm the role of the IL-6-174G>C (rs1800795) polymorphism as a genetic marker of clinical response to tocilizumab at 3 months. Our results showed that of all the variables studied, only concomitant treatment with methotrexate influenced the response to tocilizumab.

No conflict of interest

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.