Effect of IL6 -174 G/C Gene Polymorphism on Response to Interleukin-6 Blocking Therapy in Systemic Juvenile Idiopathic Arthritis.

Abstract

Objective: The main objective of this study is to analyze and evaluate the association of IL6-174 G/C gene polymorphisms with response to interleukin-6 blockade in Egyptian patients with systemic juvenile idiopathic arthritis, and to assess the effect of other factors on treatment response as well as long-term efficacy of treatment with Tocilizumab. Methods: Sixty systemic JIA patients (37 males and 23 females with median age at onset 5.2 years) who received IL-6 blockade (Tocilizumab) were recruited. The overall response to treatment with IL-6 blockade was assessed according to: 1) Clinical response, 2) switch (or no switch) to another biological DMARD therapy following IL-6 blockade, 3) achievement of clinically inactive disease within 6 months of IL-6 blockade, 4) improvement in disease activity measured using the modified JADAS-10, and 5) achievement of a glucocorticoid-free state. In addition, basic demographic, laboratory data, characteristics of the disease course and IL6 polymorphisms were assessed.Results: Three IL6 -174 genotypes, including, GG, GC, and CC were found with higher frequencies of GC genotype. These genotypes had non-significant association with the response of sJIA patients to IL-6 blockade in this cohort study. Moreover, a longer time frame from disease onset to diagnosis was associated with poorer long-term treatment response. Conclusion. No significant impact of IL6 -174 G/C gene polymorphisms on treatment response to IL6 blockade therapy in sJIA Egyptian patients, providing evidence of a “window of opportunity” for improved long-term treatment response with shorter time from the disease onset to diagnosis.