Chronic mucocutaneous candidiasis: what can we conclude about IL-17 antagonism?

Purpose: IL-17 antagonists are effective for psoriasis in clinical trials, but long-term safety is not fully characterized. Since chronic mucocutaneous candidiasis (CMC) is caused by defects in the IL-17 pathway, CMC risk data have been touted as providing reassurance about the safety of IL-17 antagonism.Methods: We performed a literature review to identify patients with CMC and compared the prevalence of cancer in these patients to the reported 5-year prevalence.Results: There was a higher prevalence of oropharyngeal (2.5% vs. 0.028%; p<.0001) and esophageal cancer (1.9% vs. 0.013%; p<.0001) in patients with CMC. There were no reports of cancer in 31 patients with CMC caused by an isolated IL-17 deficiency (IL-17F, IL-17RA, IL17RC); however, a study would need over 1000 patients to detect even a 10-fold increase in the most common malignancy of CMC patients.Conclusions: There is evidence that some forms of CMC are associated with an increase in cancer. While CMC is heterogeneous, our findings suggest that we cannot use CMC data to reassure patients on the long-term safety of IL-17 antagonists beyond the safety results from clinical trials, and perhaps caution should be taken with the development of candidiasis in patients taking these medications.