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Published on: December 19, 2019
Anti-TNF agent etanercept augments UV-induced skin cancer development in SKH-1 mice
Ercan Calıskan1, Mehmet Gamsızkan2,3, Aslan Yurekli1,4
1Department of Dermatology, Gulhane School of Medicine, Health Sciences University, Ankara, Turkey.
Background:
Despite being employed in the treatment of inflammatory disorders for more than 20 years all over the world, data regarding photocarcinogenic risks of anti-TNF agents is scarce.
Objective:
To assess photocarcinogenic potential of anti-TNF agents.
Methods:
This was a placebo controlled, split-body (UVB-treated versus -untreated) study on mice. Treatment groups were infliximab (n = 11), etanercept (n = 11), cyclosporine (n = 11) and vehicle control (n = 11). Agents were introduced on the 10th week of phototherapy and continued through 24th week. The macroscopic, histological and immunohistochemical analysis of test sites were carried out.
Results:
Overall 132 tumors were detected on test sites. All of these tumors developed on UV-exposed sides. Histologic examination of these tumors was compatible with keratinocytic neoplasia in 128, mastocytosis in 3, epidermal cyst in 1. Median tumor burden in the UVB exposed areas for ETN, IFX, CYC, and control groups were 14.91, 10.20, 6.28, and 3.14 cm2, respectively. ETN group demonstrated both higher tumor burden and keratinocytic neoplasia numbers than controls (p = .03, p = .025). Although there were 1.8 and 1.7 times more keratinocytic neoplasms in IFX and CYC groups compared to controls, these differences didn't reach statistically significant levels (p = .14; p = .19).
Conclusion:
This study points out to a significant photocarcinogenic potential of anti-TNF agent etanercept.
Insights
The study found that etanercept, a TNF inhibitor, significantly increased tumor development when exposed to UV radiation in mice. This suggests a potential photocarcinogenic risk associated with this widely used anti-TNF agent.
Area of Science:
- Immunology
- Dermatology
- Oncology
Background:
- Anti-tumor necrosis factor (TNF) agents are widely used for inflammatory conditions.
- Data on the photocarcinogenic risks of anti-TNF agents remains limited.
- Understanding these risks is crucial for patient safety.
Purpose of the Study:
- To evaluate the photocarcinogenic potential of anti-TNF agents.
- To compare the effects of infliximab, etanercept, and cyclosporine on UV-induced tumor development.
- To assess histological and immunohistochemical changes in response to treatment and UV exposure.
Main Methods:
- A placebo-controlled, split-body study was conducted on mice.
- Mice were exposed to UVB radiation.
- Treatment groups included infliximab, etanercept, cyclosporine, and a vehicle control.
- Agents were administered starting in week 10 of phototherapy.
Main Results:
- A total of 132 tumors developed on UV-exposed sites.
- The etanercept (ETN) group showed significantly higher tumor burden and keratinocytic neoplasia compared to controls (p=0.03, p=0.025).
- Infliximab (IFX) and cyclosporine (CYC) groups exhibited increased keratinocytic neoplasms but did not reach statistical significance.
Conclusions:
- Etanercept demonstrates a significant photocarcinogenic potential.
- The findings highlight the need for caution when using anti-TNF agents, particularly etanercept, in patients with UV exposure.
- Further research is warranted to elucidate the mechanisms of photocarcinogenesis associated with anti-TNF therapy.
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