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

Abstract

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.

Genetic variants found in paediatric oncology patients with severe chemotherapy-induced toxicity: A case series

“…24,25 An interesting approach is adopted by Grželj et al who showed a possible association between MTX efficacy and ABCC2 polymorphism (rs717620) in patients diagnosed with psoriasis who received low-dose MTX therapy. 26 In this study, the authors demonstrated that MTX drug survival has been significantly longer in patients carrying a T allele in ABCC2 (rs717620, C > T) than patients carrying ABCC2 (rs717620, C > T) CC genotype who discontinued their treatment due to a lack of treatment response (hazard ratio, 0.606; 95% confidence interval, 0.380-0.967; p = 0.036). However, in paediatric oncology it is common to administrate high-dose (HD) MTX (dose >500 mg/m 2 ) that could potentially lead to prolonged MTX exposure in paediatric patients carrying an ABCC2 (rs717620, C > T) variant.…”

Towards Personalized Medicine in Psoriasis: Current Progress

“… 26 A study analyzing the drug survival of MTX in 117 patients showed ABCC2 rs717620 genotype was significantly associated with drug survival, with variant T allele associated with longer drug survival. 27 Fan et al performed a study to assess if polymorphisms of the annexin A6 (ANxA6) gene, that confers psoriasis susceptibility, were associated with response to MTX. 28 They found out that the rs11960458 polymorphism was statistically significantly associated with response to MTX both in the short (12 weeks) and long-term (1 year).…”

The Impact of ABCC2 -24C>T Gene Polymorphism on Graft Survival in Kidney Transplant Recipients

“…Risk factors for the development of graft survival with the presence of acute graft rejection and/or ATN included the genetic polymorphisms studied, demographic characteristics such as age, baseline BMI and underlying comorbidities as well as transplantrelated factors and ADR due to immunosuppressive regimen (Table 3). Genetic factors were included to determine their effects on the model as well as all variables that demonstrated a p-value of <0.25 [27]. Following a multiple logistic analysis, the wildtype ABCC2 -24C>T C allele (adjusted Odd Ratios [aOR]: 27.675, 95% confidence interval [CI]: 1.204, 636.151), presence of DGF (aOR: 49.214, 95% CI: 2.366, 1023.731) and CMV infection (aOR: 18.097, 95% CI: 2.036, 160.867) resulted in an increased risk of graft survival with complications (Table 3).…”