Effectiveness of Subcutaneous Methotrexate in Chronic Plaque Psoriasis

March 2016 | Volume 15 | Issue 3 | Original Article | 345 | Copyright © March 2016


Paul Devakar Yesudian MRCP,a Joyce Leman FRCP,b Periasamy Balasubramaniam MRCP,a
Andy W. Macfarlane FRCP,a Firas Al-Niaimi MRCP,c Christopher E. M. Griffiths FRCP MD FMedSci,c
Arthur David Burden MD,b and Richard B. Warren FRCP PhDc

aBetsi Cadwaladr University Health Board, Bodelwyddan, UK
bWestern Infirmary, Glasgow, UK
cDermatology Centre, Salford Royal Hospital NHS Foundation Trust, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

Abstract
BACKGROUND: Oral methotrexate (MTX) has been a first line systemic agent in the treatment of chronic plaque psoriasis (CPP) for more than 50 years. Parenteral MTX, administered as a subcutaneous (SC) injection has gained favour in recent years. The effectiveness of SC MTX has been proven in rheumatological conditions but there has been no assessment of its role in CPP.
METHODS: We retrospectively reviewed case notes of 85 patients prescribed SC MTX for psoriasis in three dermatology centres in the UK (Betsi Cadwaladr University Health Board, Western Infirmary, Glasgow, and Salford Royal NHS Foundation Trust). Audit department approval was sought and granted.
RESULTS: A total of 85 patients (44 male; 41 female; age range 14 – 78 years, mean 44 years; 79 Caucasian, 6 Asian) with CPP were identified. The average duration of psoriasis was 19 years [range 3 - 60 years]. Co-morbidities included depression, diabetes mellitus, hypertension, epilepsy, obesity, ischaemic heart disease, and hyperlipidaemia; 29 patients had no associated co-morbidities. Psoriatic arthritis was noted in 18 patients.
Previous treatments included phototherapy (both narrow band ultraviolet B [TLO1] and psoralen and ultraviolet A [PUVA])(n=60), oral MTX (n=82), ciclosporin (n=37), acitretin (n=19), fumaric acid esters (n=20), hydroxycarbamide (n=6), mycophenolate mofetil (n=2), and repeated in-patient admissions (n=2). Oral MTX was stopped due to nausea (n=43), ineffectiveness (n=13) or partial response (n=11), headache (n=3), increased liver enzymes (n=2), and lethargy (n=2). The median number of systemic agents used prior to SC MTX was 3 (mean 2.65, range 1 to 6 agents). The weekly dose of SC MTX varied between 7.5mg to 30mg (mean 18.5mg, median 20mg) and had been used for 2 months to 67 months (mean 14 months; median 9 months). Folic acid supplementation was used in every patient. The patients were reviewed between 6 weeks to 3 months once treatment was fully established. Using a pre-determined “adjective list” (where specific adjectives were used to denote those who responded or did not respond to treatment), patients were classified as “responders” (n=59) or “non-responders” (n=26).
CONCLUSION: This study suggests that SC MTX is an effective option in patients with CPP who have failed oral MTX and could be a worthwhile consideration prior to commencement of a biologic agent. Furthermore, the SC route may be a viable first choice of MTX administration. A randomised controlled trial comparing oral and SC MTX is required to validate these findings.

J Drugs Dermatol. 2016;15(3):345-349.

INTRODUCTION

Methotrexate (MTX) is a commonly used agent in the treatment of moderate to severe chronic plaque psoriasis (CPP). Its effectiveness has been established in the dermatological literature.1-4 Even though the use of parenteral MTX was first described in the 1960’s,5-9 it was not a routine treatment modality for the next 40 years. Initially, parenteral MTX was given as an intra-muscular injection, which was difficult to self-administer and therefore needed medical input on a weekly basis. Pharmacies were also reluctant to dispense this formulation as it was difficult to produce and carried the risk of toxicity with even a slight deviation in dose. Subcutaneous (SC) and intramuscular injections deliver bioequivalent doses of MTX, with the former more convenient and less painful compared to the latter.10 The development of a patient-administered SC MTX was therefore an innovation that has helped popularise this therapy.
There is good evidence of the efficacy of SC MTX in the rheumatological literature,11,12 SC MTX has a better bioavailability compared to oral MTX and is also known to cause fewer gastro-intestinal side-effects.13 It is also documented to be more effective than oral MTX at the same dose in rheumatoid arthritis. 14,15 Even though a recent review has recommended the use of SC MTX in CPP, there is no published clinical series evaluating its role in psoriasis.16 This study aimed to collect data from three UK dermatology centres to assess the effectiveness of SC MTX in CPP, focusing on those who had
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