Polymorphism in gene for ABCC2 transporter predicts methotrexate drug survival in patients with psoriasis

Grželj, Jasna (author), Marovt, Maruška (author), Marko, Pij B. (author), Mlinarič-Raščan, Irena (author), Gmeiner, Tanja (author), Šmid, Alenka (author)

Background and Objectives: Methotrexate is widely prescribed for the treatment of moderateto-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.

• Language: English
• Keywords: psoriasis, drug survival, methotrexate, pharmacogenetics
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2021
• Number of pages: 12 str.
• Numbering: Vol. 57, iss. 10, art. 1050
• PID: 20.500.12556/RUL-136272
• UDC: 616.517-085
• ISSN on article: 1648-9144
• DOI: 10.3390/medicina57101050
• COBISS.SI-ID: 79774723
• Publication date in RUL: 21.04.2022

Record is a part of a journal

• Title: Medicina
• Publisher: MDPI
• ISSN: 1648-9144
• COBISS.SI-ID: 6754623

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 01.10.2021

Secondary language

• Language: Slovenian
• Keywords: metotreksat, zdravljenje luskavice, psoriaza, farmakogenetika

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P1-0208
• Name: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Funder: EC - European Commission
• Funding programme: European Regional Development Fund
• Project number: C333-19-952061
• Acronym: EATRIS-TRI.SI