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Pharmacokinetics and pharmacodynamics
PKP-022 The KCNMB1 (A >G) (RS703505) genetic variant and the efficacy of tocilizumab in rheumatoid arthritis patients
  1. X Díaz-Villamarín1,
  2. CL Dávila-Fajardo1,
  3. MDC Gónzalez-Medina1,
  4. MJ Soto-Pino1,
  5. E Sánche-Gómez2,
  6. A Acuña3,
  7. A Gómez-Martín4,
  8. LJ Martínez-González4,
  9. I Casas-Hidalgo1,
  10. J Cabeza-Barrera1
  1. 1Instituto de Investigación Biosanitaria de Granada Hospital Universitario San Cecilio–Granada–Spain, Department of Clinical Pharmacy, Granada, Spain
  2. 2Juan Ramón Jiménez Hospital, Department of Clinical Pharmacy, Huelva, Spain
  3. 3Complejo Hospitalario de Jaén, Department of Clinical Pharmacy, Jaén, Spain
  4. 4Centre for Genomics and Oncological Research GENYO- Pfizer-University of Granada-Andalusian Regional Government, Genomics Unit, Granada, Spain

Abstract

Background Tocilizumab (TCZ) is a humanised monoclonal antibody inhibitor of interleukin-6 receptor, indicated in combination with methotrexate in the treatment of rheumatoid arthritis (RA) in patients with inadequate response or intolerance to prior therapy.

Purpose The aim of our study was to explore the potential role of KCNMB1 genetic polymorphisms as a predictor of tocilizumab efficacy in RA patients.

Material and methods The KCNMB1 (A >G) (rs703505) genetic variant was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 24 weeks with the use of the 28 joint disease activity score criteria (DAS28). Clinical response was evaluated at 14 weeks using DAS28 and good response and remission were classified according to EULAR criteria. EULAR good response was defined as a change in DAS28 >1.2 and DAS28 ≤3.2. EULAR remission was defined as DAS28 ≤2.6 at 14 weeks. Statistical analysis was performed using SPSS v.20.

Results Clinical data for 140 tocilizumab treated patients were obtained. Patients were aged (mean±SD) 53.25 ± 12.42 years; 79% were female. Mean DAS28 at baseline was 5.71 ± 1.13. KCNMB1-GG genetic polymorphism was associated with EULAR good response (GG vs no GG p = 0.26, OR=0.37, 95% CI 0.14 to 0.93) and with EULAR remission (p = 0.01, OR=0.29, 95% CI 0.09 to 0.87).

Conclusion Our results confirm that KCNMB1 (A >G) rs703505 polymorphisms could be useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.

No conflict of interest.

https://doi.org/10.1136/ejhpharm-2016-000875.425

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