Cargando…

Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to def...

Descripción completa

Detalles Bibliográficos
Autores principales: Grželj, Jasna, Marovt, Maruška, Marko, Pij B., Mlinarič-Raščan, Irena, Gmeiner, Tanja, Šmid, Alenka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539794/
https://www.ncbi.nlm.nih.gov/pubmed/34684087
http://dx.doi.org/10.3390/medicina57101050
_version_ 1784588833229111296
author Grželj, Jasna
Marovt, Maruška
Marko, Pij B.
Mlinarič-Raščan, Irena
Gmeiner, Tanja
Šmid, Alenka
author_facet Grželj, Jasna
Marovt, Maruška
Marko, Pij B.
Mlinarič-Raščan, Irena
Gmeiner, Tanja
Šmid, Alenka
author_sort Grželj, Jasna
collection PubMed
description Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan–Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380–0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice.
format Online
Article
Text
id pubmed-8539794
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85397942021-10-24 Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis Grželj, Jasna Marovt, Maruška Marko, Pij B. Mlinarič-Raščan, Irena Gmeiner, Tanja Šmid, Alenka Medicina (Kaunas) Article Background and Objectives: Methotrexate is widely prescribed for the treatment of moderate-to-severe psoriasis. As drug survival encompasses efficacy, safety, and treatment satisfaction, such studies provide insights into successful drug treatments in the real-life scenario. The objective was to define methotrexate drug survival and reasons for discontinuation, along with factors associated with drug survival, in a cohort of adult patients with moderate-to-severe plaque psoriasis. Materials and Methods: Data on methotrexate treatment were extracted from our institutional registry. Drug survival was estimated by Kaplan–Meier analysis, and predictors of drug survival were analyzed by Cox proportional hazards regression. Results: We included 133 patients treated with methotrexate. Due to significant effects of the year of treatment initiation, drug survival analysis was performed for 117 patients who started methotrexate in 2010 or later. Median methotrexate drug survival was 11.0 months. Overall, 89% of patients discontinued treatment, with over half of these (51%) due to lack of efficacy. Significantly longer drug survival was seen for patients who discontinued treatment due to lack of efficacy versus drug safety (p = 0.049); when stratified by sex, this remained significant only for women (p = 0.002). The patient ABCC2 rs717620 genotype was significantly associated with drug survival in both univariate log-rank and multivariate Cox regression analyses, with variant T allele associated with longer drug survival (hazard ratio, 0.606; 95% confidence interval, 0.380–0.967; p = 0.036). Conclusions: We have identified the novel association of patient ABCC2 rs717620 genotype with methotrexate drug survival. This pharmacogenetic marker might thus help in the management of psoriasis patients in daily practice. MDPI 2021-10-01 /pmc/articles/PMC8539794/ /pubmed/34684087 http://dx.doi.org/10.3390/medicina57101050 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Grželj, Jasna
Marovt, Maruška
Marko, Pij B.
Mlinarič-Raščan, Irena
Gmeiner, Tanja
Šmid, Alenka
Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title_full Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title_fullStr Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title_full_unstemmed Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title_short Polymorphism in Gene for ABCC2 Transporter Predicts Methotrexate Drug Survival in Patients with Psoriasis
title_sort polymorphism in gene for abcc2 transporter predicts methotrexate drug survival in patients with psoriasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539794/
https://www.ncbi.nlm.nih.gov/pubmed/34684087
http://dx.doi.org/10.3390/medicina57101050
work_keys_str_mv AT grzeljjasna polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis
AT marovtmaruska polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis
AT markopijb polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis
AT mlinaricrascanirena polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis
AT gmeinertanja polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis
AT smidalenka polymorphismingeneforabcc2transporterpredictsmethotrexatedrugsurvivalinpatientswithpsoriasis