Association Between −174 Interleukin-6 Gene Polymorphism and Biological Response to Rituximab in Several Systemic Autoimmune Diseases

Abstract

Rituximab has become a pivotal treatment for systemic autoimmune diseases. The aim of this study was to determine whether the genetic variant -174 IL-6 contributes to differences in the response to rituximab in patients with systemic autoimmune diseases, including systemic lupus erythematosus (SLE), inflammatory myopathies, anti-neutrophil cytoplasmic antibody-mediated vasculitis, systemic sclerosis, Sjöegren's syndrome, rheumatoid arthritis, and autoimmune hemolytic anemia. DNA samples from 144 Spanish patients with different systemic autoimmune diseases receiving rituximab were genotyped for -174 IL-6 (rs1800795) gene polymorphism using the TaqMan(®) allelic discrimination technology. Six months after the first infusion with rituximab, we evaluated the response to the drug: 60.4% of the patients showed a complete response, partial 27.8%, and 11.8% did not respond to the treatment. The CC genotype frequency was significantly increased in nonresponders with respect to responders (23.5% vs. 7.1%, respectively; p=0.049; odds ratio (OR)=4.03, 95% confidence intervals (CI) 0.78-16.97). According to the genotype distribution, rituximab was effective in 69.2% of the CC carriers, 91.9% of the CG carriers, and 88.4% of the GG carriers. A similar trend was observed when SLE patients were analyzed separately (27.3% carried CC homozygosis in nonresponders and 6.9% in responders; p=0.066; OR=5.10, 95% CI 0.65-31.73). Rituximab was effective in 62.5% of the CC carriers, 88.9% of the GC carriers, and 90% of the GG carriers. These results suggest that -174 IL-6 (rs1800795) gene polymorphism plays a role in the response to rituximab in systemic autoimmune diseases. Validation of these findings in independent cohorts is warranted.

Genetics of toll like receptor 9 in ANCA associated vasculitides

“…The fact that we found neither a primary association of the IL6 promotor SNP in AAV nor a significant epistatic effect between the IL6 promotor SNP and any TLR9 SNP does not rule out a potential role of IL6 genotypes in AAV pathology and treatment (eg, with rituximab16). Such mechanisms should be evaluated further.…”

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review

“…Across RCTs and cohorts, five studies included participants aged 15–17 years [8] , [9] , [26] , [27] , [28] , while seven studies only included patients aged 18 years or older [29] , [30] , [31] , [32] , [33] . In five studies, mean age was not reported [13] , [34] , [35] , [36] , [37] . The follow-up duration varied from 24 to 78 weeks (6–18 months) for RCTs and 6–60 months for cohort studies.…”

Melanoma and Rituximab: An Incidental Association?

“…Its off-label use is increasing in inflammatory and autoimmune diseases such as pemphigus, systemic lupus erythematosus, dermatomyositis, ANCA-associated vasculitis, idiopathic membranous nephropathy, multiple sclerosis, autoimmune haemolytic anaemia or inflammatory myopathies [1]. Thus, the number of patients exposed to this treatment is continually increasing.…”