Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study.
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(3-5) species are more active.


OBJECTIVE
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.
St John's Institute of Dermatology, Division of Genetics and Molecular Medicine, King's College London, London, UK.
R T
RT
Woolf
S L
SL
West
M
M
Arenas-Hernandez
N
N
Hare
A M
AM
Peters van Ton
C M
CM
Lewis
A M
AM
Marinaki
J N W N
JN
Barker
C H
CH
Smith
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000009:adverse effects; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood; D008875:Middle Aged; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000097:blood; D011446:Prospective Studies; D011565:Psoriasis / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
D015415:Biomarkers; D003879:Dermatologic Agents; D011099:Polyglutamic Acid; C014085:methotrexate polyglutamate; D008727:Methotrexate