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

The Pharmacogenomics Journal volume 18, pages 167–172 (2018)Cite this article

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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.

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Acknowledgements

We acknowledge all the patients which participated in the study, the professionals from the Complejo Hospitalario Universitario de Granada that contributed to the management of the samples, especially the nursing team from the Rheumatology Department and to Dr Manuela Expósito-Ruiz, for her excellent advice with statistics. The results of this investigation are part of the doctoral thesis presented by Mar Maldonado-Montoro at the University of Granada, Programme of Doctorate in Pharmacy. This work was partly supported by a contract for Marisa Cañadas-Garre (Técnicos de Apoyo Subprogram. CA12/00097) from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad.

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Authors and Affiliations

  1. Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain

    M Maldonado-Montoro, M Cañadas-Garre & M Ángel Calleja-Hernández

  2. UGC Rheumatology, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Granada, Spain

    A González-Utrilla

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  1. M Maldonado-Montoro
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Correspondence to M Cañadas-Garre.

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Maldonado-Montoro, M., Cañadas-Garre, M., González-Utrilla, A. et al. Influence of IL6R gene polymorphisms in the effectiveness to treatment with tocilizumab in rheumatoid arthritis. Pharmacogenomics J 18, 167–172 (2018). https://doi.org/10.1038/tpj.2016.88

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