IL-1b, IL-6, and TNF gene polymorphisms do not affect the treatment outcome of rheumatoid arthritis patients with leflunomide Andrzej Pawlik 1 , Magdalena Herczyñska 2 , Mateusz Kurzawski 1 , Krzysztof Safranow 3 , Violetta Dziedziejko 3 , Zygmunt Juzyszyn 1 , Marek DroŸdzik 1 Abstract: Leflunomide is an isoxazole derivative that is structurally and functionally unrelated to other known immunomodulatory drugs. Pre- vious studies have revealed that therapy with leflunomide causes decreased production of mediators such as IL-1b, IL-6, and TNF-a, which are involved in inflammatory process. The aim of the present study was to examine whether the polymorphisms in genes IL1B, IL6, and TNF may affect treatment outcomes in RA patients treated with leflunomide. The study was carried out on 129 patients (106 women, 23 men, mean age 52.9 ± 11.03) diagnosed with RA and treated with leflu- nomide 20 mg daily. Clinical improvement was evaluated according to the American College of Rheumatology (ACR) 20% and 50% response criteria. There were no statistically significant associations between the studied genotypes and improvement of disease activity parameters. The results of the present study suggest that IL1b, IL6, and TNF gene polymorphisms are not significant factors influencing the ther- apy outcome of RA patients with leflunomide. Key words: rheumatoid arthritis, leflunomide, cytokines, polymorphism Introduction Rheumatoid arthritis (RA) is a common autoimmune disease in which a combination of risk alleles from different susceptibility genes predisposes the patient to development of clinical symptoms following expo- sure to as yet unknown environmental factors. Treat- ment of this disease is mainly based on drugs which modulate its course, and previous studies have shown that genetic factors influence the response to drugs used in RA therapy [21]. Pharmacogenetics focuses on the genetic variations responsible for drug metabo- lism, drug transport, and drug targets to determine how these variations result in inherited alterations in medication outcomes [11, 14]. Identification of ge- netic determinants of drug efficacy and toxicity will be valuable because they can be ascertained in the in- dividual patient before initiation of therapy [1, 12]. 281