INTRODUCTION
Immunosuppressive and immunomodulatory medications are widely utilized in dermatology to treat chronic inflammatory skin conditions. However, their use in patients with active or prior malignancy remains an area of uncertainty. Certain immunosuppressive medications have been linked to an increased incidence and mortality from melanoma and non-melanoma skin cancer (NMSC), and may contribute to recurrence of primary malignancies.1 Clinical trials have historically excluded patients with malignancy, and carcinogenesis often requires prolonged follow-up, leaving limited evidence to guide treatment decisions.2,3 Therefore, dermatologists may hesitate to initiate or continue systemic immunosuppressive therapy in this population. This article reviews current literature regarding the use and safety of immunosuppressive and immunomodulatory medications in this population. Table 1 summarizes key evidence on malignancy risk for each therapeutic class with odds ratios and confidence intervals when available.
Biologics: Tumor Necrosis Factor Alpha Inhibitors
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine. Elevated levels are characteristic of several inflammatory skin diseases, due to keratinocyte proliferation, immune cell activation, and adhesion molecule upregulation.4 TNF-α inhibitors (TNFis), including infliximab, adalimumab, etanercept, and certolizumab pegol, are FDA-approved for psoriasis, and adalimumab is approved for hidradenitis suppurativa.5 Off-label uses include pemphigus vulgaris and pyoderma gangrenosum.5
TNFis have been associated with an increased cancer risk in psoriasis. Nested case-control analyses in the PSOLAR study (n=1260) found long-term (>12 months) TNFi therapy was associated with increased malignancy risk, excluding NMSC (odds ratio (OR), 1.54; 95% CI, 1.10–2.15).6 However, in analyses restricted to monotherapy, this association was no longer statistically significant (OR, 1.29; 95% CI, 0.84–1.98).6 A Korean study of 191,678 patients with psoriasis found overall cancer
Biologics: Tumor Necrosis Factor Alpha Inhibitors
Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine. Elevated levels are characteristic of several inflammatory skin diseases, due to keratinocyte proliferation, immune cell activation, and adhesion molecule upregulation.4 TNF-α inhibitors (TNFis), including infliximab, adalimumab, etanercept, and certolizumab pegol, are FDA-approved for psoriasis, and adalimumab is approved for hidradenitis suppurativa.5 Off-label uses include pemphigus vulgaris and pyoderma gangrenosum.5
TNFis have been associated with an increased cancer risk in psoriasis. Nested case-control analyses in the PSOLAR study (n=1260) found long-term (>12 months) TNFi therapy was associated with increased malignancy risk, excluding NMSC (odds ratio (OR), 1.54; 95% CI, 1.10–2.15).6 However, in analyses restricted to monotherapy, this association was no longer statistically significant (OR, 1.29; 95% CI, 0.84–1.98).6 A Korean study of 191,678 patients with psoriasis found overall cancer
