Methotrexate treatment for patients with psoriasis and risk of cutaneous melanoma: a nested case-control study.

BACKGROUND: Cutaneous malignant melanoma (CMM) is a highly immunogenic tumour. Patients with an impaired immune system have an enhanced risk for CMM and a worse prognosis. Methotrexate (MTX) is an anti-inflammatory and immunosuppressive drug frequently used to treat patients with psoriasis. An association between MTX and risk of CMM has previously been demonstrated in patients with rheumatoid arthritis. OBJECTIVES: To investigate whether MTX increases the risk of CMM among patients with psoriasis. METHODS: A nested case-control investigation from a Swedish cohort of patients with psoriasis was conducted. Data were obtained from available Swedish registers and included 395 patients with psoriasis who had previously been cancer-free and had a first CMM in the time period from 1 January 2010 to 31 December 2016. A total of 10 randomly selected cancer-free patients with psoriasis were matched per case with respect to age (same birth year) and sex. The accumulated MTX doses in both groups were obtained. Crude odds ratios (ORs) for the proportion of MTX in the respective group were calculated using conditional logistic regression analyses. RESULTS: Of 395 patients with psoriasis who had CMM, 97 (25%) had filled a prescription of MTX; of 3950 controls, the corresponding number was 954 (24%). In a conditional logistic regression analysis, no association between MTX exposure (ever use) and risk for CMM was observed (OR 1·0, 95% confidence interval 0·8-1·3). Moreover, no indication of a dose-response association was observed. CONCLUSIONS: In this Swedish nested case-control study, the use of MTX was not associated with an enhanced risk for CMM. These findings are reassuring for dermatologists in everyday clinical practice. What is already known about this topic? Methotrexate (MTX) treatment has been linked to an increased risk for cutaneous malignant melanoma (CMM) in an Australian cohort of patients with rheumatoid arthritis. In a previous retrospective Swedish cohort investigation, patients who had exclusively been prescribed MTX by a dermatologist did not have an enhanced risk for CMM compared with MTX-unexposed individuals. Nevertheless, this cohort did not specifically include patients with psoriasis. What does this study add? This Swedish nested case-control investigation included 395 previously cancer-free patients with psoriasis who had CMM (cases) and 3950 matched cancer-free patients with psoriasis (controls). No association between MTX exposure and risk for CMM in patients with psoriasis was observed. The results are reassuring for dermatologists using MTX to treat patients with psoriasis. Linked Comment: Haugaard and Egeberg. Br J Dermatol 2020; 183:608-609.

Secukinumab treatment in new-onset psoriasis: aiming to understand the potential for disease modification - rationale and design of the randomized, multicenter STEPIn study.

BACKGROUND: To date, biological treatments have been assessed in subjects with a long-term history of psoriasis and previous failures to systemic and topical therapies. In rheumatoid arthritis and other immune-mediated inflammatory diseases, early intensive systemic treatment prolongs treatment-free remission. We hypothesize that, by treating patients with psoriasis early with an effective systemic therapy, we may be able to alter the clinical outcome and the natural course of the disease. The STEPIn study (NCT03020199) investigates early intervention with secukinumab versus narrow-band ultraviolet B (nb-UVB) phototherapy in subjects with new-onset psoriasis. OBJECTIVE: To determine whether early intervention with either nb-UVB treatment or secukinumab in subjects with new-onset plaque psoriasis might modify the natural course of the disease. METHODS: One hundred and sixty subjects aged 18-50 years with new-onset (≤12 months) moderate-to-severe plaque psoriasis and naïve to systemic treatment and phototherapy will be randomized to secukinumab 300 mg or nb-UVB. The Main Study has two treatment arms: Arm A1, subcutaneous secukinumab 300 mg at baseline, Weeks 1, 2, 3 and 4, and every 4 weeks thereafter until and including Week 52; Arm B1, one/two cycles of nb-UVB for 12 weeks each (maximum 28-week break between cycles). After treatment discontinuation, patients will be followed up and monitored for disease activity up to Week 208. A Mechanistic Sub-study will assess immunological changes and pathogenic tissue-resident memory T cells in skin biopsies. CONCLUSIONS: STEPIn is the first study to investigate whether early intensive treatment in new-onset psoriasis can modify the long-term natural course of the disease and thus become a novel treatment strategy for patients with psoriasis.

Methotrexate treatment and risk for cutaneous malignant melanoma: a retrospective comparative registry-based cohort study.

BACKGROUND: Methotrexate (MTX) is frequently used as an immunosuppressive drug in inflammatory diseases. It is controversial and it has not been thoroughly investigated whether MTX increases the risk of cutaneous malignant melanoma (CMM). OBJECTIVES: The aim of the present study was to investigate whether MTX exposure increases the risk for CMM. METHODS: A retrospective cohort study was conducted using statistics from the National Board of Health and Welfare. All patients over 18 years in the time period August 2005 to December 2014 that were dispensed MTX from Swedish pharmacies were registered (n = 101 966). For every MTX-exposed patient, five age- and sex-matched patients who had been dispensed a random drug other than MTX during the same time period were randomly selected (n = 509 279). The lists were matched with the Swedish Cancer Registry. RESULTS: Overall, a small but statistically significant (P < 0·001) risk increase for CMM was observed in MTX-exposed patients compared with patients without MTX exposure. The Kaplan-Meier estimates for the 5-year risk of CMM was 0·48% [95% confidence interval (CI) 0·43-0·53] in the MTX-exposed group and 0·41% (95% CI 0·39-0·43) in the MTX-unexposed group. However, in a subgroup analysis, the difference between the groups was preserved only in women older than 70 years at treatment start. Moreover, there was no significant difference in incidences between the MTX-exposed and MTX-unexposed patients in the time period. CONCLUSIONS: Our results suggest a small but significant increase in risk for CMM in patients treated with MTX. However, the risk increase observed was considerably lower than in earlier observations.

Effect of climate therapy at Gran Canaria on vitamin D production, blood glucose and lipids in patients with psoriasis.

BACKGROUND: Climate therapy (heliotherapy) of psoriasis is an effective and natural treatment. Ultraviolet radiation (UVB) from the sun improves psoriasis and induces vitamin D(3) synthesis. OBJECTIVE: The aim of the study was to investigate the effect of climate therapy on vitamin D(3) synthesis, blood glucose, lipids and vitamin B12 in psoriasis patients. METHODS: Twenty Caucasian patients (6 women and 14 men; mean age, 47.2 years; range, 24-65) with moderate to severe psoriasis [mean Psoriasis Area and Severity Index (PASI) score 9.8; range, 3.8-18.8] received climate therapy at the Gran Canarias for 3 weeks. Blood samples were drawn before and after 15 days of sun exposure. In addition, the patients' individual skin UV doses based on UV measurements were estimated. RESULTS: Sun exposure for 15 days lead to a 72.8% (+/- 18.0 SD) reduction in the PASI score in psoriasis patients. Although no direct correlation was observed between PASI score improvement and UVB dose, the sun exposure improved the vitamin D, lipid and carbohydrate status of the patients. The serum concentrations of 25-hydroxyvitamin D [25(OH)D] increased from 57.2 +/- 14.9 nmol/L before therapy to 104.5 +/- 15.8 nmol/L (P < 0.0001) after 15 days of sun exposure; the serum levels of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] increased from 146.5 +/- 42.0 to 182.7 +/- 59.1 pmol/L (P = 0.01); the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol decreased from 2.4 to 1.9 (P < 0.001); and the haemoglobin A(1)c (HbA(1)c) levels decreased from 5.6 +/- 1.7% to 5.1 +/- 0.3% (P < 0.0001). CONCLUSION: Climate therapy with sun exposure had a positive effect on psoriasis, vitamin D production, lipid and carbohydrate status.