Supplemental Files for "Increased risk of nonmelanoma skin cancer with cyclosporine, methotrexate, TNF-α inhibitors, and interleukin (IL)-12/23 inhibitor, but not with IL-17 or IL-23 inhibitors in psoriasis patients"

ABSTRACT

Background:
People with psoriasis are at increased risk for nonmelanoma skin cancers (NMSC) and melanoma. Conventional immunosuppressants and TNF-α inhibitors may further increase skin malignancy risk, while the risks of other biologics are less clear.

Objectives:
Quantify skin malignancy risks in psoriatic patients treated with cyclosporine, methotrexate, apremilast, TNF-α inhibitors, IL-12/23, IL-17, and IL-23 inhibitors.

Methods:
Using the TriNetX database, psoriasis patients without skin cancer risk factors who received at least two years or at least five years of systemic treatment were compared to non-systemically treated psoriasis patients. Cyclosporine, methotrexate, and TNF-α inhibitors were also compared with other psoriasis biologics. NMSC and melanoma over two and five years were evaluated using multivariable Cox proportional hazards.

Results:
Compared with non-systemically treated patients, cyclosporine, methotrexate, TNF-α inhibitors, and the IL-12/23 inhibitor showed increased NMSC risk, whereas IL-17 inhibitors demonstrated a reduced risk. Compared with patients treated with cyclosporine, methotrexate, and TNF-α inhibitors, IL-17 and IL-23 inhibitors demonstrated a reduced NMSC risk. Only cyclosporine was associated with elevated melanoma risk.

Limitations:
Unmeasured factors include psoriasis severity, ultraviolet radiation exposure, medication adherence, or dosing.

Conclusions:
Systemic therapies for psoriasis vary in skin malignancy risk, with IL-17 and IL-23 inhibitors having the lowest NMSC risk.