Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in rheumatoid arthritis

• Published in: The pharmacogenomics journal Vol. 18; no. 1; pp. 167 - 172
• Main Authors: Maldonado-Montoro, M, Cañadas-Garre, M, González-Utrilla, A, Ángel Calleja-Hernández, M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2018; Nature Publishing Group
• Subjects: 692/53/2423; 692/699/249/1313; Adult; Analysis; Antibodies, Monoclonal, Humanized - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Biomedical and Life Sciences; Biomedicine; Complications and side effects; Dosage and administration; Drug therapy; Female; Gene Expression; Genetic aspects; Genotypes; Health risk assessment; Human Genetics; Humans; Immunosuppressive agents; Interleukin 6; Interleukin 6 receptors; Interleukins; Male; Middle Aged; Monoclonal antibodies; Odds Ratio; Oncology; original-article; Pharmacotherapy; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide - genetics; Psychopharmacology; Receptors, Interleukin-6 - genetics; Remission; Remission Induction - methods; Retrospective Studies; Rheumatoid arthritis; Severity of Illness Index; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Tocilizumab; Treatment Outcome; Spain
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2016.88

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; CI 95% : 0.35, 0.75; P =0.001), LDA (OR: 0.41; CI 95% : 0.24, 0.72; P =0.002) and improvement in DAS28 ( B =−0.32; CI 95%) : −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; CI 95% : 0.79, 1.20; P =1.5 × 10 −14 ). Those patients who were carriers of AA genotypes for rs12083537 (OR: 13.0; CI 95% : 2.31, 72.91; P =0.004) and CC for rs11265618 (OR: 12.15; CI 95% : 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.