Are interleukin 17 and interleukin 23 inhibitors associated with malignancies?—Insights from an international population-based study

Abstract

Background: Cancer risk after long-term exposure to interleukin (IL)-23 inhibitors (IL-23i) and IL-17 inhibitors (IL-17i) remains to be delineated. Objective: To evaluate the risk of malignancies in patients with psoriasis treated with IL-23i and IL-17i relative to those prescribed tumour necrosis factor inhibitors (TNFi) during the first 5 years following drug initiation. Methods: A global population-based cohort study included two distinct analyses comparing patients with psoriasis under different therapeutic modalities; (i) new users of IL-17i(n = 15,331) versus TNFi (n = 15,331) and (ii) new users of IL-23i (n = 5832) versus TNFi (n = 5832). Results: Patients prescribed IL-17i experienced a decreased risk of non-Hodgkin lymphoma (NHL; HR, 0.58; 95% CI, 0.40–0.82; p = 0.002), colorectal cancer (HR, 0.68; 95% CI, 0.49–0.95; p = 0.024), hepatobiliary cancer (HR, 0.68; 95% CI, 0.58–0.80; p < 0.001), ovary cancer (HR, 0.48; 95% CI, 0.29–0.81; p = 0.005), melanoma (HR, 0.52; 95% CI, 0.37–0.73; p < 0.001), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48–0.67; p < 0.001). IL-23i was associated with a reduced risk of NHL (HR, 0.39; 95% CI, 0.19–0.78; p = 0.006), hepatobiliary cancer (HR, 0.44; 95% CI, 0.31–0.62; p < 0.001) and BCC (HR, 0.76; 95% CI, 0.57–0.99; p = 0.046). In a sensitivity analysis comparing patients managed by IL-17i and IL-23i with their biologic-naïve counterparts, these classes were associated with decreased risk of several malignancies. Conclusion: IL-17i and IL-23i are associated with decreased risk of several malignancies. These findings should be considered prior to the prescription of biologics.