ABSTRACT
Both psoriasis and methotrexate are associated with an increased risk of nonmelanoma skin cancer. The effect of methotrexate on the development of nonmelanoma skin cancer in patients with psoriasis is currently unknown. To evaluate this relationship, a systematic review of the literature was conducted using databases including Ovid Medline (from 1946), Scopus (from 1970), and Embase (from 1974) through June 2019. Observational comparative and case-control studies comparing psoriasis patients treated with methotrexate to those not treated with methotrexate with data on the subsequent development of nonmelanoma skin cancer in both cohorts were included based on prespecified criteria. Two reviewers analyzed all studies for relevant data, which were analyzed using OpenMeta-Analyst statistical software. Quality was assessed with the Newcastle-Ottawa method. Nine cohort and case-control comparative studies of 1,486 screened abstracts met the inclusion criteria. Of 11,875 reported patients with psoriasis, 2,192 were taking methotrexate. A meta-analysis demonstrated an odds ratio of 2.8 (95% confidence interval = 1.47-5.39; p = 0.002) for nonmelanoma skin cancer development in patients with psoriasis taking methotrexate compared with those not taking methotrexate. Based on these findings, psoriasis patients treated with methotrexate are at a significantly increased (2.8 times higher) risk of developing nonmelanoma skin cancer. Risk counseling can improve healthcare outcomes in patients with psoriasis.