Is Pharmacogenetic Panel Testing Applicable to Low-Dose Methotrexate in Rheumatoid Arthritis? – A Case Report

Abstract

Purpose Pharmacogenetic (PGx) panel testing could help to determine the heritable component of a rheumatoid arthritis (RA) patient’s susceptibility for therapy failure and/or adverse drug reactions (ADRs) from methotrexate (MTX). Considering the literature mentioning the potential applicability of PGx panel testing within MTX regimens, we discuss the case of a patient who was treated with MTX, suffered from ADRs, and obtained a reactive PGx panel testing. Genotyping We used a commercial PGx panel test involving the ABC-transporters P-glycoprotein (P-gp; gene: ABCB1 ), and breast cancer resistance protein (BCRP; gene: ABCG2 ), the solute carriers reduced folate carrier 1 (RFC1; gene: SLC19A1 ), and organic anion transporting polypeptide 1B1 (OATP1B1; gene: SLCO1B1 ), and the enzymes inosine triphosphatase (ITPA), and glutathione transferase P1 (GSTP1). In addition, we genotyped the patient for the enzymes 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICAR)/inosine monophosphate (IMP) cyclohydrolase (gene name: ATIC ), gamma-glutamyl hydrolase (gene name: GGH ) and methylenetetrahydrofolate reductase (gene name: MTHFR ). Results The PGx profile of the patient revealed genetic variants in SLC19A1, ABCB1, and MTHFR, which may explain the ADRs experienced during the treatment with MTX and a potentially lower efficacy of MTX. Based on our interpretation of the PGx profile, we recommended the patient to avoid MTX in the future. Conclusion The MTX pathway is complex, which makes the interpretation of genetic variants affecting metabolism challenging. A reactive PGx panel test was applicable to explain ADRs experienced during MTX treatment for a patient with RA. However, the clinical utility of PGx-guided MTX treatment in a primary care setting is still limited. In order to base a recommendation for MTX on PGx data, we need genome-wide association studies, large prospective multicenter studies and PGx studies, which analyze different multi-gene haplotypes and gene-drug-drug interactions for MTX.

ABCC1, ABCG2 and FOXP3: Predictive Biomarkers of Toxicity from Methotrexate Treatment in Patients Diagnosed with Moderate-to-Severe Psoriasis

“…Previous studies have revealed the influence of various SNPs on the toxicity of MTX in patients with autoimmune diseases, such as MTHFR, MTR, ABCC1, ABCC2, and ABCG2 [ 72 , 73 , 74 ]. However, the existing evidence on the influence of genetics on MTX toxicity in patients with PS is limited.…”

A Guide to a Pharmacist-Led Pharmacogenetic Testing and Counselling Service in an Interprofessional Healthcare Setting

“…Following the referral by the treating physician, the recruited patients underwent the process, as depicted in Figure 1 . Individual cases from the series were published as case reports [ 21 , 22 , 23 , 24 , 25 , 26 ]. The work experience that was gathered within the observational case series study was used to further refine the PGx service over the duration of 3 years between 2019 and 2021, and was based on feedback from patients and treating physicians that was further elaborated in a mixed methods study [ 27 ].…”

Genotyping of Patients with Adverse Drug Reaction or Therapy Failure: Database Analysis of a Pharmacogenetics Case Series Study

“…7 This study was designed to compile case reports to acquire experience with the application of PGx in Swiss primary and secondary care as a basis for the implementation of a standard of procedure. After three years of collecting those patient cases and publishing selected individual case reports, [14][15][16][17][18][19] we aimed to perform a database analysis of all gathered data of the study population.…”