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426 SPECIAL REPORT Methotrexate Use and Monitoring in Patients with Psoriasis: A Consensus Report Based on a Danish Expert Meeting Line RAABY 1 , Claus ZACHARIAE 2 , Monika ØSTENSEN 3 , Lene HEICKENDORFF 4 , Peter THIELSEN 5 , Henning GRØNBÆK 6 , Lone SKOV 2 , Nini KYVSGAARD 7 , Jakob T. MADSEN 8 , Michael HEIDENHEIM 9 , Anne T. FUNDING 10 , Gitte STRAUSS 11 , Rune LINDBERG 12 and Lars IVERSEN 1 Departments of 1 Dermatology, 4 Clinical Biochemistry, 6 Hepatology and Gastroenterology and 7 Paediatrics, Aarhus University Hospital, Aarhus, Departments of 2 Dermatology and Allergy and 5 Hepatology and Gastroenterology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark, 3 National Advisory Unit on Pregnancy and Rheumatic Diseases, Department of Rheumatology, Trondheim University Hospital, Trondheim, Norway, 8 Department of Dermatology and Allergy Centre, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, 9 Department of Dermatology, Copenhagen University Hospital, Roskilde, 10 Dermatology Clinic, Hudlaegecenter Nord, Aalborg, 11 Dermatology Clinic, Copenhagen, and 12 Dermatology Clinic, Odense, Denmark Methotrexate (MTX) has been used in the treatment of psoriasis and other dermatological diseases for more than 50 years. However, there is limited evidence re- garding its effect, dose and monitoring, and a lack of consensus regarding how the drug should be used in daily practice. Although the use of MTX is governed by guidelines, such as the European S3-Guidelines and the National Institute for Health and Care Excellence (NICE) guideline, it is important to discuss and adjust these guidelines to national standards. An expert mee- ting was held in Denmark at the end of 2014, in order to reach consensus regarding the use of MTX in der- matological practice in Denmark. Participants included dermatologists, hepatologists, paediatricians, clinical biochemists and a rheumatologist. Topics discussed were: liver disease monitoring, teratogenic effects of MTX, risk of cancer, and use of MTX in children. We report here the conclusions of this expert meeting re- garding use of MTX in dermatological practice. Key words: psoriasis; skin diseases; methotrexate. Accepted Dec 12, 2016; Epub ahead of print Dec 13, 2016 Acta Derm Venereol 2017; 97: 426–432. Corr: Claus Zachariae, Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, DK-2900 Hellerup, Denmark. E-mail: [email protected]; and Lars Iversen, De- partment of Dermatology, Aarhus University Hospital, DK-8000 Aarhus, Denmark. E-mail: [email protected] M ethotrexate (MTX) is a folic acid antagonist that was first used in the treatment of acute leukaemia in the early 1950s and subsequently for the treatment of solid tumours. Low-dose MTX has also been used suc- cessfully for the treatment of rheumatoid arthritis and psoriasis; and over the past 25 years, MTX has become the standard of care in the treatment of these 2 diseases (1–3). The effect of MTX was originally described as anti-proliferative, as the drug induces inhibition of purine, methionine and thymidylate synthesis, and the- reby inhibits DNA synthesis. MTX is transported into the cells by either a folate carrier or by passive diffusion, and is polyglutamated once inside the cells (4). Whereas MTX has a half-life of 5–8 h, the MTX polyglutamates are retained in cells and tissues for several weeks or doi: 10.2340/00015555-2599 Acta Derm Venereol 2017; 97: 426–432 months (5). It was suggested that low-dose MTX treat­ ment, e.g. the doses used in psoriasis, may also have anti-inflammatory effects, including increased adenosine levels, and MTX has been shown to modulate immune cells and to decrease the level of tumour necrosis factor alpha (TNFα), among other effects (3, 6). DERMATOLOGICAL USE OF METHOTREXATE MTX has been used in the treatment of moderate-to- severe psoriasis for many years; yet, the first randomized controlled trials were not performed until 2003. These studies compared MTX with cyclosporine (7, 8). MTX was later compared with different biologics in other randomized controlled trials (9–11). Even so, evidence for its effect remains limited. Yet, MTX is used for the treatment of a wide range of dermatological disorders, including pityriasis rubra pilaris, atopic dermatitis, chro- nic urticaria, pityriasis lichenoides, blistering disorders, cutaneous lupus erythematosus, localized scleroderma, vasculitis, cutaneous sarcoidosis, dermatomyositis and granuloma annulare (6). This report focuses on expe- rience with MTX in the treatment of psoriasis. For dermatological indications, MTX is used in low doses compared with those used in oncology. No studies have established the best starting or maintaining dose for dermatological indications (12), although a few studies have compared different doses of MTX in the treatment of psoriasis (13, 14). The general recommendation in psoriasis is to start at 5–15 mg once weekly, with dose escalation up to 25–30 mg weekly, depending on the clini- cal response (15, 16). The doses of MTX used for other dermatological diseases are similar to those used in pso- riasis (6). Caution is recommended when treating elderly patients and patients with impaired kidney function (15). According to the National Institute for Health and Care Excellence (NICE) guideline, the maximum treatment response is usually seen 16–24 weeks after treatment initiation, although maximal effect will occasionally be reached within 8–12 weeks of treatment with 15 mg weekly doses (16). Both the PASI75, which is equal to a 75% reduction in the skin manifestation of psoriasis, This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica.