The Use of Self-Administered Subcutaneous Methotrexate for the Treatment of Psoriasis
August 2014 | Volume 13 | Issue 8 | Original Article | 929 | Copyright © 2014
Anthony J. Chiaravalloti MDa and Bruce E. Strober MD PhDb,c
aDivision of Dermatology, SUNY Upstate Medical University, Syracuse, NY
bDepartment of Dermatology, University of Connecticut Health Center, Farmington, CT
cProbity Medical Research, Waterloo, ON, Canada
For nearly 5 decades, methotrexate has been the backbone of moderate-to-severe psoriasis treatment. The benefits of methotrexate
therapy include reliable efficacy, low cost, relative ease of administration, and its usefulness as part of combination therapy regimens,
making it a drug of choice for treating psoriasis. While methotrexate can be administered orally, intravenously, or intramuscularly, the
self-administered subcutaneous use of the drug is the most advantageous route. Subcutaneous methotrexate is associated with fewer
adverse events and higher absorption rates, accompanied by bioavailability that is both linear and predictable throughout the range of
possible doses. In addition, the subcutaneous route, when compared with oral administration, facilitates improved efficacy by
promoting higher intracellular levels of long-chain methotrexate polyglutamates. Taken together, these features allow patients the
highest probability of a successful therapeutic experience. Subcutaneous methotrexate should be considered a viable option for the
appropriate patient with moderate-to-severe psoriasis.
J Drugs Dermatol. 2014;13(8):929-931.
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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