INTRODUCTION
With nearly 50 years of use, methotrexate is a mainstay
of therapy for psoriasis. Appropriate patient
selection and careful monitoring provides safe
and reliable use for a reasonable cost.1-4 Methotrexate is effective.
In 4 large, randomized, double-blinded, controlled studies,
between 35% and 60% of treated subjects achieved a 75%
reduction in their Psoriasis Area and Severity Index (PASI) after
approximately 3 to 4 months.5-8 Methotrexate is also effective
for treating atypical variants of psoriasis such as the erythrodermic
and generalized pustular presentations.2,9,10 Contrary to the
established dogma of methotrexate as an unsafe and intolerable
medication, these same studies demonstrate the acceptable
safety and tolerability of continuous methotrexate therapy for
the majority of treated patients, while serious side effects occur
in a small minority of patients. Importantly, low-dose methotrexate
provides anti-inflammatory properties that distinguish
the drug from its use as a high-dose antineoplastic agent.5-8,11
The Practical Use of Methotrexate
The most recent guidelines from the American Academy
of Dermatology and the European Academy of Dermatology
and Venereology recommend a single weekly dose of
methotrexate in the 7.5 mg to 25 mg range. Without a clear
consensus on an optimum starting dose, the treatment patterns
are variable. In treating chronic plaque psoriasis, the
initial dosing of oral methotrexate may be cautious at 5 mg
to 10 mg weekly for the first month.12 One of the authors of
this article (Bruce E. Strober MD PhD) commonly employs
from the outset of therapy 12.5 mg to 15 mg weekly. Patients
should concurrently begin folic acid supplementation.13,14 Folic
acid decreases toxicity, increases tolerability, may provide cardiovascular benefits, and does not come at a cost of reduced
methotrexate efficacy.13-17 With regard to reducing the
occasional gastrointestinal intolerability of methotrexate, folinic
acid may be superior to folic acid.15,16,18
Proven Efficacy of Methotrexate as Monotherapy and in Combination
The ultimate efficacy of oral methotrexate can be ascertained
relatively early on in the treatment course. The majority of
PASI 75 responders after 16 weeks show a PASI 50 response
after only 8 weeks at an oral dose of 15 mg weekly. Subsequent
dose escalation to 20 mg weekly for poorly responding patients
gains relatively few additional PASI 75 responders.19
Methotrexate is also safely used in combination therapy for
the treatment of psoriasis. Adding it to etanercept results in
significantly greater efficacy than using etanercept as monotherapy.
11,20 Other studies demonstrate the increased effectiveness
of methotrexate when combined with multiple other biologics
for the treatment of rheumatoid arthritis (RA).21-24 Additionally,
methotrexate robustly enhances the efficacy of psoralen
in combination with ultraviolet light A (PUVA), dramatically
shortening the time to response.25,26 In all of these analyses,
combining methotrexate with other therapies does not significantly
compromise safety.
The Safety, Tolerability, and Monitoring of Methotrexate
Methotrexate rarely may result in myelosuppression, hepatotoxicity,
teratogenicity, and pneumonitis. While ameliorated
by folate supplementation, the occasional intolerability of
