Khalaf Kridin, MD, PhD

Credit: ResearchGate

Both interleukin (IL)-23 and IL-17 inhibitors are linked to a diminished risk of colorectal, non-Hodgkin lymphoma (NHL), hepatobiliary, melanoma, ovary cancers, and basal cell carcinoma (BCC) as compared with tumor necrosis factor inhibitors (TNFi) for those with psoriasis, according to recent findings.¹

This new data resulted from a global study conducted to assess psoriasis patients’ malignancy risk once treated with IL-23 and IL-17 inhibitors, specifically in comparison to those with TNFi prescriptions in the initial 5 years after drug initiation.

This new research was led by Khalaf Kridin, MD, PhD, from Lűbeck Institute of Experimental Dermatology at the University of Lübeck in Germany. Kridin and colleagues sought to resolve the methodological issues they had observed in studying risk of cancer with a longer-term study, given issues such as the extended time the development of malignancies can take.²

“The aim of the current study is to assess the risk of a wide assortment of malignancies in a large cohort of patients with psoriasis starting IL-23i and IL-17i treatment relative to those undergoing tumor necrosis factor inhibitor (TNFi) therapy during the first 5 years following treatment initiation,” Kridin and colleagues wrote.

Background and Findings

The investigators used a retrospective cohort design and utilized the TriNetX database to examine patients’ risk of malignancies in patients with psoriasis starting 3 different biologic agents. The database is known to be a comprehensive health research network, with data on about 117.5 million individuals over 91 healthcare organizations.

The research team screened medical records, specifically those of 117.5 million health-insured patients within the Global Collaborative Network (GCN) of TriNetX for psoriasis diagnostic codes. Three different treatment arms were created by the team and based upon the biologics used in the study: TNFi, IL-17i, and IL-23i.

Participants in the IL-17 inhibition arm were given ixekizumab, secukinumab, or brodalumab. Those in the IL-23 inhibition arm were given guselkumab, risankizumab, or tildrakizumab. TNFi arm participants received infliximab, adalimumab, certolizumab pegol, or etanercept.

The investigators’ criteria were applied to prevent overlapping exposures to several different treatment classes among the participants. The subjects were later followed over the course of 5 years in order to examine their risk of hematologic and solid malignancy development.

The research team conducted propensity score matching to balance their study arms in terms of comorbidities, previous treatments, demographic data, and other possible confounding variables. Further sensitivity analyses were planned by the team to assess the subjects’ risk of malignancies for those managed by IL-17 and IL-23 inhibitors versus biologic-naïve individuals, with matching leading to uniform distribution of the confounding variables across the study arms.

Overall, the investigators reported that those prescribed IL-17 inhibitors ended up showing a lowered risk of several different types of cancers. These malignancies included hepatobiliary cancer (HR, 0.68; 95% CI, 0.58-0.80; P<0.001), colorectal cancer (HR, 0.68; 95% CI, 0.49-0.95; P=0.024), and NHL (HR, 0.58; 95% CI, 0.40-0.82; P=0.002).

Additional malignancies noted by the research team which had lower risk included melanoma (HR, 0.52; 95% CI, 0.37-0.73; P<0.001), ovary cancer (HR, 0.48; 95% CI, 0.29-0.81; P=0.005), and basal cell carcinoma (BCC; HR, 0.57; 95% CI, 0.48-0.67; P<0.001).They found that IL-23 inhibitors were linked to a diminished risk of hepatobiliary cancer (HR, 0.44; 95% CI, 0.31-0.62; P<0.001), NGL (HR, 0.39; 95% CI, 0.19-0.78; P=0.006), and BCC (HR, 0.76; 95% CI, 0.57-0.99; P=0.046).

The investigators’ sensitivity analysis compared subjects that had been treated with IL-17 and IL-23 inhibitors to individuals who were biologic-naïve and this showed a lowered risk of several different types of malignancies linked with these classes of medications.

“The current study sheds important light on the long-term safety of IL-17i and IL-23i with regard to carcinogenesis,” they wrote. “The safety of this class should be further investigated among patients with a prior history of malignancies before drug initiation.”

References

1. ^{Kridin, K., Abdelghaffar, M., Mruwat, N., Ludwig, R.J. and Thaçi, D. (2023), Are interleukin 17 and interleukin 23 inhibitors associated with malignancies? – Insights from an international population-based study. J Eur Acad Dermatol Venereol. Accepted Author Manuscript. https://doi.org/10.1111/jdv.19520.}
2. ^{Garcia-Doval I, Descalzo MA, Mason KJ, Cohen AD, Ormerod AD, Gómez-García FJ, et al. Cumulative exposure to biological therapy and risk of cancer in patients with psoriasis: a meta-analysis of Psonet studies from Israel, Italy, Spain, the U.K. and Republic of Ireland. Br J Dermatol [Internet]. 2018 Oct 1 [cited 2022 Oct 24];179(4):863–71. Available from: https://pubmed.ncbi.nlm.nih.gov/29723914/.}