ABSTRACT
A half century has passed since the serendipitous observation by Gubner that the folic acid aminopterin improved the lesions of psoriasis during a trial to assess its anti-inflammatory effects in patients with psoriatic arthritis (2). These observations were transferred into clinical trials utilizing a daily dosage schedule of aminopterin (3). In the late 1950s methotrexate (MTX) replaced aminopterin. During the next two decades alternative dosage schedules were developed based on cell cycle information and cancer chemotherapy concepts. Until the development of psoralen/ultraviolet A treatment (PUVA) in 1975, UVB phototherapy and methotrexate were the only effective treatments for moderate-to-severe psoriasis. Methotrexate was approved for psoriasis by the Food and Drug Administration (FDA) without the usual, at least by current standards, large double-blind clinical trials. Methotrexate usage for psoriasis appeared to be grandfathered in, in part related to guidelines for MTX therapy for psoriasis referred to below. Thus there are no large clinical trials to quantitate the efficacy and safety of the drug for the treatment of psoriasis. Its usefulness is based on many years of clinical experience and numerous clinical retrospective studies with more emphasis on side effects than efficacy (4-7). In recent years it has been estimated that 25,000-30,000 patients were receiving methotrexate therapy in the United States, although current data are not available.
