A MULTICENTER 12-WEEK OPEN STUDY OF A LIPID-SOLUBLE FOLATE ANTAGONIST, PIRITREXIM IN SEVERE PSORIASIS

An open, 12-week, multicentre study was conducted to assess the effica cy of piritrexim isethionate in the treatment of severe psoriasis. Pir itrexim isethionate is a lipid-soluble dihydrofolate reductase inhibit or which cannot form polyglutamates, and may be as effective as methot rexate in the treatment of psoriasis. If, as is suspected, but as yet unproven, methotrexate polyglutamates are responsible for the hepatoto xicity of methotrexate, piritrexim should be less hepatotoxic, and may offer an alternative to methotrexate therapy. Fifty-five patients wer e enrolled, of whom 41 completed the study. Patients were allocated to receive either 150, 225, 300, or 450 mg of piritrexim weekly, in divi ded doses over 72 h (low-dose groups, 150 and 225 mg), or over 36 h (3 00 and 450 mg groups). Twenty-four of the 41 patients who completed th e study had a greater than 50% improvement in the severity of their ps oriasis, as demonstrated by a reduction in the Psoriasis Severity Scor e, a measure analogous to the PASI scoring system. Adverse events were common, but mild, and were controlled by dose reduction. Piritrexim a ppears to be an effective therapy for severe psoriasis at doses of 300 and 450 mg weekly, in three divided doses over 36 h.