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

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

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.

• Jezik: Angleški jezik
• Ključne besede: psoriasis, drug survival, methotrexate, pharmacogenetics
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2021
• Št. strani: 12 str.
• Številčenje: Vol. 57, iss. 10, art. 1050
• PID: 20.500.12556/RUL-136272
• UDK: 616.517-085
• ISSN pri članku: 1648-9144
• DOI: 10.3390/medicina57101050
• COBISS.SI-ID: 79774723
• Datum objave v RUL: 21.04.2022

Gradivo je del revije

• Naslov: Medicina
• Založnik: MDPI
• ISSN: 1648-9144
• COBISS.SI-ID: 6754623

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.
• Začetek licenciranja: 01.10.2021

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: metotreksat, zdravljenje luskavice, psoriaza, farmakogenetika

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin

• Financer: EC - European Commission
• Program financ.: European Regional Development Fund
• Številka projekta: C333-19-952061
• Akronim: EATRIS-TRI.SI