Squamous-cell cancer of the skin in patients given PUVA and ciclosporin: nested cohort crossover study

Background Immunosuppressive treatments have been associated with an increa sed risk of skin cancer, especially in patients who have had organ transpla nts. We aimed to assess the risk of skin cancer in patients taking the cicl osporin who had been exposed to psoralen and ultraviolet-A light (PUVA) and other treatments for severe psoriasis. Methods We did a nested cohort crossover study of 28 participants in the PU VA follow-up study who were on ciclosporin to compare the frequency of squa mous-cell carcinoma before and after first use of ciclosporin. We also anal ysed the entire PUVA study cohort (1380) to assess the relation between use of this drug and frequency of squamous-cell carcinoma. Findings In the 5 years before first use, six of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (aver age follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell car cinomas. In the nested cohort, after adjustment for amount of exposure to P UVA and methotrexate, incidence of tumours was seven times higher after fir st ciclosporin use than in the previous 5 years (incidence rate ratio 6.9 [ 95% CI 4.3-11]). Multivariate, analysis of the entire cohort showed that ri sk of squamous-cell carcinoma after any use of ciclosporin is close to that recorded for at least 200 PUVA treatments (3.1 [2.6-3.7] and 2.8 [2.6-3.2] , respectively). Interpretation The risk of squamous cell cancer of the skin is increased by ciclosporin in patients with psoriasis who have been exposed to PUVA. Such risks should be balanced against the effectiveness of the drug and possibl e newer immunosuppressive agents.