Immunosuppressive treatments such as ciclosporin have been associated with an increased risk of skin cancer, although most previous research has focused on patients who have had organ transplants.

In the early 1970s, a new treatment for the severe skin condition psoriasis was introduced -- combination of the light-sensitive drug psoralen and exposure to ultraviolet-A radiation along with immunosupressive drugs, including ciclosporin and methotrexate.

This combination treatment is used to treat severe psoriasis cases.

Isabelle Marcil and Robert Stern from Beth Israel Deaconess Medical Center, Boston, aimed to assess the risk of skin cancer in patients taking ciclosporin who had been exposed to PUVA and other treatments for severe psoriasis.

The frequency of squamous-cell skin cancer for 28 patients (who had previously taken part in the PUVA study) and who were on ciclosporin was compared before and after their first use of ciclosporin. The investigators also analyzed the entire PUVA study population (1,380 patients) to assess the relation between ciclosporin use and frequency of squamous-cell cancer.

In the 5 years before first ciclosporin use, six of 28 (21%) ciclosporin users developed a total of 20 squamous cell cancers. After ciclosporin use (average follow-up 6 years), 13 (46%) developed a total of 169 squamous-cell carcinomas.

After adjustment for amount of exposure to PUVA and methotrexate, incidence of tumors was seven times higher after first ciclosporin use than in the previous 5 years.

Any use of ciclosporin was associated with a three-fold increase in risk of squamous-cell cancer, and use for at least 3 months was associated with a nearly four-fold increase.

Patients were at substantially greater risk with 3 months or longer use of ciclosporin than with exposure to at least 200 PUVA treatments. Long-term use of methotrexate was associated with lower risk than either any ciclosporin or high-dose PUVA use

Robert Stern comments, “New immunomodulatory therapies hold great promise for improving the treatment of severe psoriasis. However, the great increase in skin cancer risk we have documented in patients with severe psoriasis treated with the first immunomodulatory therapy for this disease strongly argues that careful assessment of the long-term safety of new immunologically based treatments for psoriasis is needed.”

(Reference: The Lancet, 29 September 2001)

28-Sep-2001