title: Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in rheumatoid arthritis.
abstract: In the present study, we aimed to investigate the influence of clinical parameters and single-nucleotide polymorphisms of interleukin-6 receptor (rs12083537, rs2228145, rs4329505 and rs11265618) on response to tocilizumab, TCZ (European League Against Rheumatism (EULAR) response, remission, low disease activity (LDA) and improvement of DAS28). We performed a retrospective cohort study in patients with Rheumatoid Arthritis (RA) treated with TCZ for 12 months. Multivariable analysis showed that the only variable independently associated to satisfactory EULAR response (odds ratio (OR): 0.61; 95% of confidence interval (CI)95%: 0.42, 0.88; P=0.008), remission (OR: 0.51; CI95%: 0.35, 0.75; P=0.001), LDA (OR: 0.41; CI95%: 0.24, 0.72; P=0.002) and improvement in DAS28 (B=-0.32; CI95%): -0.47, -0.17; P=7.5 × 10-5) at 12 months was lower number of previous biological therapy (BT). High baseline DAS28 was also associated with a greater decrease in DAS28 at 12 months of treatment (B=0.99; CI95%: 0.79, 1.20; P=1.5 × 10-14). Those patients who were carriers of AA genotypes for rs12083537 (OR: 13.0; CI95%: 2.31, 72.91; P=0.004) and CC for rs11265618 (OR: 12.15; CI95%: 2.18, 67.81; P=0.004) had better LDA response at 12 months of treatment with TCZ. In conclusion, RA patients treated with TCZ showed better EULAR response, remission, LDA and DAS28 improvement rates when a lower number of BT were previously administered. The AA genotype for rs12083537 and CC for rs11265618 polymorphisms for may act as predictors of good response LDA.
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Maldonado-Montoro
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Cañadas-Garre
authors.affiliation: UGC Rheumatology, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.
authors.forename: A
authors.initials: A
authors.lastname: González-Utrilla
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Ángel Calleja-Hernández
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000235:genetics*; D012074:Remission Induction / Q000379:methods; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; C508603:IL6R protein, human; D019947:Receptors, Interleukin-6; C502936:tocilizumab