TY - JOUR
T1 - Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis
T2 - A single-centre prospective study
AU - Woolf, R. T.
AU - West, S. L.
AU - Arenas-Hernandez, M.
AU - Hare, N.
AU - Peters Van Ton, A. M.
AU - Lewis, C. M.
AU - Marinaki, A. M.
AU - Barker, J. N.W.N.
AU - Smith, Catherine H.
PY - 2012/7
Y1 - 2012/7
N2 - Background: Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG 1-5). MTXPG 1-5 inhibit enzymes of the folate-purine- pyrimidine pathways, and longer-chain MTXPG 3-5species are more active. Objectives: To determine the pattern of erythrocyte 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. Methods: This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG 1-5 concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved ≥ 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks. Results: MTXPG levels were measured in 14-33 patients at each time point. All MTXPG 1-5 species were detected at week 4 of therapy. Steady state for long-chain MTXPG 3-5 and total MTXPG 1-5 was achieved by week 24. MTXPG 3 emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG 2-5, MTXPG 3-5 and MTXPG 4-5; R = 0.76-0.95, P < 1.55 × 10 -5). Age, renal function and sex were not significant determinants of MTXPG 3 concentration. No significant association was identified between MTXPG and adverse events or responder status. Conclusions: This is the first study to demonstrate the prospective accumulation of MTXPG 1-5 in patients with psoriasis. 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. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response.
AB - Background: Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG 1-5). MTXPG 1-5 inhibit enzymes of the folate-purine- pyrimidine pathways, and longer-chain MTXPG 3-5species are more active. Objectives: To determine the pattern of erythrocyte 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. Methods: This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG 1-5 concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved ≥ 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks. Results: MTXPG levels were measured in 14-33 patients at each time point. All MTXPG 1-5 species were detected at week 4 of therapy. Steady state for long-chain MTXPG 3-5 and total MTXPG 1-5 was achieved by week 24. MTXPG 3 emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG 2-5, MTXPG 3-5 and MTXPG 4-5; R = 0.76-0.95, P < 1.55 × 10 -5). Age, renal function and sex were not significant determinants of MTXPG 3 concentration. No significant association was identified between MTXPG and adverse events or responder status. Conclusions: This is the first study to demonstrate the prospective accumulation of MTXPG 1-5 in patients with psoriasis. 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. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response.
UR - http://www.scopus.com/inward/record.url?scp=84863332183&partnerID=8YFLogxK
U2 - 10.1111/j.1365-2133.2012.10881.x
DO - 10.1111/j.1365-2133.2012.10881.x
M3 - Article
C2 - 22309614
AN - SCOPUS:84863332183
SN - 0007-0963
VL - 167
SP - 165
EP - 173
JO - British Journal of Dermatology
JF - British Journal of Dermatology
IS - 1
ER -