Skip to content

Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis (MTXPG)

Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis (MTXPG) 1

Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study. MTXPG(1-5) in patients initiated on oral methotrexate for psoriasis, and to investigate the potential utility of MTXPGs as markers of compliance and/or clinical response. The detection of MTXPGs early in therapy and the establishment of a steady state with continuous treatment may offer measuring of MTXPG as a test to monitor patient compliance with therapy. Genetic variation in efflux transporters influences outcome to methotrexate therapy in patients with psoriasis. Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis (MTXPG). This study is enrolling participants by invitation only.

Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis (MTXPG) 2Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study. A pilot study of pharmacokinetically guided dosing of oral methotrexate in the initial phase of psoriasis treatment. This can be a factor contributing to the variability of therapeutic and toxic effects. Cutaneous ulceration typically precedes other markers of toxicity. Methotrexate is licensed for the treatment of severe psoriasis, psoriatic arthritis, rheumatoid arthritis, and a number of malignancies, including: childhood acute lymphoblastic leukemia, lymphoproliferative disorders, choriocarcinoma, and various solid organ tumors. Given the clinical implications of widespread use of MTX in RA, various studies have evaluated the role of potential biomarkers in predicting treatment effectiveness of MTX. The ideal biomarker for treatment response and toxicity should be widely available, easily measurable, accurate, reproducible, and inexpensive. RBC MTX polyglutamate (MTX PG) concentrations have been proposed as biomarkers of MTX response in patients with RA 30.

(RA) and psoriasis, and more recently, inflammatory bowel disease (IBD). Methotrexate (MTX) is a cornerstone of treatment in a wide variety of inflammatory conditions, including juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). However, owing to its narrow therapeutic index and the considerable interpatient variability in clinical response, monitoring of adherence to MTX is important. Polymorphisms in folate, pyrimidine, and purine metabolism are associated with efficacy and toxicity of methotrexate in psoriasis. Therapeutic and toxic response to low-dose methotrexate (MTX) in the treatment of autoimmune disease continues to be highly variable, resulting in a critical need to identify predictive biomarkers of response. (TS) was measured as markers of pharmacological activity of MTX in an erythroblastoid cell line. Cellular levels of MTX and its polyglutamate metabolites (MTX-PGtotal) were determined by liquid chromatography tandem mass spectrometry and normalized to cellular protein content. (1999) Urinary adenosine and aminoimidazolecarboxamide excretion in methotrexate-treated patients with psoriasis.

Methotrexate Polyglutamates As A Marker Of Patient Compliance And Clinical Response In Psoriasis: A Single-centre Prospective Study

Methotrexate Polyglutamates as a Marker of Clinical Response and Toxicity in the Treatment of Psoriasis (MTXPG) 3There are no reliable clinical or molecular markers of response to therapy. Therapeutic outcome of rheumatoid arthritis (RA) patients treated with methotrexate (MTX) can be modulated by thymidylate synthase (TS) levels, which may be altered by genetic polymorphisms in TS gene ( TYMS ). MTXPG: methotrexate polyglutamates; R: repeat; SLC: solute carrier; Moreover, one study in Psoriasis, a disease where MTX is used in similar doses than RA, 6bp allele demonstrated a trend for non-response, however, this study included Caucasian and non-Caucasian patients 45. MTX, methotrexate; MTXPG, methotrexate polyglutamate; SHMT1, serine hydroxymethyl transferase; SLC19A1, solute carrier 19A1; THF, tetrahydrofolate; TYMS, thymidylate synthase. Methotrexate (MTX) remains the drug of choice for treatment of RA. The enzyme most effectively inhibited by methotrexate polyglutamates (MTXPGs) is ATIC. Polyglutamation of MTX enhances the intracellular retention of MTX promoting the inhibition of folate, methionine and adenosine pathways and, the de novo synthesis of purines and pyrimidines, which is considered crucial for anti-inflammatory and antiproliferative therapeutic effects of MTX 13,15,16,17. Median MTX treatment duration was 28.0 months with a median dose of 15. Genotype Approach and Clinical Response to Methotrexate (MTX). Methods of predicting methotrexate efficacy and toxicity. For example, MTX is currently one of the most widely prescribed drugs for the treatment of rheumatoid arthritis, psoriasis, and cancer (Weinblatt et al, Eng. Although MTX is among the best tolerated of the disease-modifying anti-rheumatic drugs, a major drawback of MTX therapy is a troublesome inter-patient variability in the clinical response and an unpredictable appearance of side-effects including gastrointestinal disturbances, alopecia, elevation of liver enzymes, and bone marrow suppression (Weinblatt et al, Arthritis Rheum.

Methotrexate Polyglutamates As A Marker Of Patient Compliance And Clinical Response In Psoriasis: A Single-centre Prospective Study

Target of Rapamycin Complex I; MTX, methotrexate; MTXPG, methotrexate polyglutamate; OCT, organic cation transporter; Methotrexate (MTX) is widely prescribed to treat inflammatory conditions including psoriasis, where it is the recommended first-line systemic therapy in moderate-to-severe disease. If a positive correlation is identified between MTXPG levels and clinical response we aim to define a therapeutic dose range of MTXPG.