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Chronic mucocutaneous candidiasis: what can we conclude about IL-17 antagonism?
Kevin K Veverka1, Steven R Feldman1
1a Department of Dermatology Wake Forest School of Medicine , Winston-Salem , NC , USA.
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.
Insights
Chronic mucocutaneous candidiasis (CMC) patients show increased oropharyngeal and esophageal cancer risk. This suggests caution is needed when using CMC data to assess the long-term safety of IL-17 antagonists.
Area of Science:
- Immunology
- Oncology
- Dermatology
Background:
- Interleukin-17 (IL-17) antagonists show efficacy in psoriasis clinical trials.
- Long-term safety data for IL-17 antagonists are limited.
- Chronic mucocutaneous candidiasis (CMC) arises from IL-17 pathway defects, leading to its use in safety assessments.
Purpose of the Study:
- To evaluate cancer risk in patients with chronic mucocutaneous candidiasis (CMC).
- To determine if CMC data can reassure about IL-17 antagonist safety.
Main Methods:
- Literature review to identify CMC patients.
- Comparison of cancer prevalence in CMC patients versus general population data.
Main Results:
- Significantly higher prevalence of oropharyngeal (2.5% vs. 0.028%) and esophageal cancer (1.9% vs. 0.013%) in CMC patients.
- No cancers reported in 31 CMC patients with isolated IL-17 deficiency.
- Over 1000 patients needed to detect a 10-fold increase in common malignancies.
Conclusions:
- Certain forms of CMC are linked to increased cancer risk.
- CMC data cannot fully reassure about long-term IL-17 antagonist safety beyond clinical trials.
- Caution is advised regarding candidiasis development in patients using IL-17 antagonists.
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