title: A multicentre 12-week open study of a lipid-soluble folate antagonist, piritrexim in severe psoriasis.
abstract: An open, 12-week, multicentre study was conducted to assess the efficacy of piritrexim isethionate in the treatment of severe psoriasis. Piritrexim isethionate is a lipid-soluble dihydrofolate reductase inhibitor which cannot form polyglutamates, and may be as effective as methotrexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatotoxicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients were enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divided doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (300 and 450 mg groups). Twenty-four of the 41 patients who completed the study had a greater than 50% improvement in the severity of their psoriasis, as demonstrated by a reduction in the Psoriasis Severity Score, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim appears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.
authors.affiliation: Department of Dermatology, Western Infirmary, Glasgow, U.K.
authors.forename: W
authors.initials: W
authors.lastname: Perkins
authors.forename: R E
authors.initials: RE
authors.lastname: Williams
authors.forename: J P
authors.initials: JP
authors.lastname: Vestey
authors.forename: M J
authors.initials: MJ
authors.lastname: Tidman
authors.forename: A M
authors.initials: AM
authors.lastname: Layton
authors.forename: W J
authors.initials: WJ
authors.lastname: Cunliffe
authors.forename: E M
authors.initials: EM
authors.lastname: Saihan
authors.forename: M R
authors.initials: MR
authors.lastname: Klaber
authors.forename: V K
authors.initials: VK
authors.lastname: Manna
authors.forename: H
authors.initials: H
authors.lastname: Baker
mesh_terms: D004334:Drug Administration Schedule; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008099:Liver / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D012720:Severity of Illness Index; D014839:Vomiting / Q000139:chemically induced
chemical_list: D005493:Folic Acid Antagonists; D011743:Pyrimidines; C024530:piritrexim