Nonmelanoma Skin Cancer Risks Are Higher When Using Methotrexate for Psoriasis: Study

Patients with psoriasis taking methotrexate are nearly 3 times as likely to develop non-melanoma skin cancer than patients not taking the treatment.

Patients with psoriasis who are treated with methotrexate (MTX) face a significantly higher risk of developing nonmelanoma skin cancer (NMSC), new results of a systematic review and meta-analysis show.

Findings were published in the journal Cureus.

Psoriasis is associated with an increased risk of number of comorbid conditions, including cardiovascular disease, metabolic syndrome, solid organ cancers and skin cancers, though “the risk of skin cancer development is currently not well quantified,” authors wrote.

For patients receiving systemic oral immune-regulating therapies, the risk of NMSC is further heightened.

MTX, an antineoplastic and anti-inflammatory antifolate medication that acts by reversibly inhibiting dihydrofolate reductase, an enzyme required for adequate cell division, is a primary treatment for moderate-to-severe psoriasis. The treatment is also used to control systemic inflammation for other autoimmune conditions.

Previous research has shown patients with psoriasis taking MTX have an increased risk of NMSCs, while this risk may increase with prolonged usage. In addition, the link between overall cancer risk and psoriasis rises with the condition’s severity across all age groups.

Some research has suggested the risk might be comparable to cancer risk in individuals who have undergone organ transplants, authors said.

“Given the high frequency with which MTX is used in patients with psoriasis, this lack of conclusive data about the actual risk represents a gap in our knowledge and affects a large population of patients who could potentially benefit from more comprehensive counseling,” they added.

In an effort to better quantify the extent of NMSC risk associated with MTX therapy researchers searched Ovid Medline, Scopus and Embase through June 2019 for relevant literature. All included studies were observational comparative and case control analyses that compared patients with psoriasis treated with MTX to those not treated with MTX.

A total of 9 cohort and case-control comparative studies met inclusion criteria.

Of the nearly 12,000 patients with psoriasis, 2192 were taking MTX.

Overall, “a meta-analysis demonstrated an odds ratio of 2.8 (95% CI, 1.47-5.39; P = .002) for nonmelanoma skin cancer development in patients with psoriasis taking methotrexate compared with those not taking methotrexate,” authors found.

They suggest risk counseling may improve health care outcomes in individuals with psoriasis, as increased awareness of anhigh risk could decrease morbidity and mortality.

Educating those with psoriasis taking MTX could also affect tumor burden. To modify risk, researchers suggest these patients undergo increased screening for skin cancer with regular full-body skin examinations, more thorough counselling on appropriate skin protection, and more education on the signs of NMSC.

To the authors knowledge, the current analysis marks the most comprehensive data to date on the risk of NMSC in patients with psoriasis treated with MTX.

“However, the limited number of high-quality investigational studies analyzing this association between MTX, psoriasis, and NMSC indicates that further research is needed,” they noted.

The analysis also included all patients taking MTX regardless of other concurrent regimens, like nonbiologic systemic medications, phototherapy and biologics. Researchers were thus unable to estimate the role of other therapies on the development of skin carcinomas.

“Because MTX has been used in the treatment of psoriasis for more than 50 years and is still frequently used, the information provided in this systematic review and meta-analysis is extremely useful when counseling patients beginning MTX regimens,” they said.“Future studies that further elucidate the effect of MTX on NMSC development could be beneficial.”

Overall, counselling regarding these findings can help decrease patient comorbidity from NMSC, improve healthcare outcomes and decrease costs for these patients, authors concluded.


Lang Houser ME, Stewart JR, and Brewer JD. Psoriasis patients treated with methotrexate have an increased risk of nonmelanoma skin cancer: a systematic review and meta-analysis. Cureus. Published online April 5, 2023. doi:10.7759/cureus.37174

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