No Causal Link between Phosphodiesterase Type 5 Inhibition and Melanoma

PURPOSE: To examine the association between phosphodiesterase type 5 (PDE5) inhibitor use and melanoma by 1) conducting a systematic review of observational studies; and 2) determining if low PDE5A gene expression in human melanoma correlated with decreased overall survival. MATERIALS AND METHODS: A systematic search of observational studies examining the association between PDE5 inhibitor use and melanoma was performed through ClinicalTrials.gov, the Cochrane Library, EMBASE, PubMed, and Web of Science databases, and seven eligible studies were identified. PDE5A gene expression was analyzed with RNA sequencing data from 471 human melanoma samples obtained from The Cancer Genome Atlas. RESULTS: Four studies reported a positive association between PDE5 inhibitor use and melanoma, and three studies found no correlation. RNA sequencing data analysis revealed that under-expression of the PDE5A gene did not impact clinical outcomes in melanoma. CONCLUSIONS: There is currently no evidence to suggest that PDE5 inhibition in patients causes increased risk for melanoma. The few observational studies that demonstrated a positive association between PDE5 inhibitor use and melanoma often failed to account for major confounders. Nonetheless, the substantial evidence implicating PDE5 inhibition in the cyclic guanosine monophosphate (cGMP)-mediated melanoma pathway warrants further investigation in the clinical setting.

Is It Possible to Discontinue Tumor Necrosis Factor Antagonists after Psoriasis Remission?

Tumor necrosis factor (TNF) antagonists are highly effective treatments for psoriasis. These agents provide the opportunity to improve disease activity and achieve clinical remission. Despite its efficacy, long-term use of biologics is associated with high financial costs and possibly life-threatening adverse events. Recently, there has been an increasing interest in discontinuing TNF antagonists in patients with psoriasis who have achieved a positive clinical response. However, there is a paucity of data and clinical guidelines concerning the cessation TNF antagonists in psoriasis treatment. Several factors, including cost, subsequent treatment efficacy, relative risks, and tolerability, should be considered before the decision is made to discontinue TNF antagonists. Well-designed clinical trials are necessary to identify factors that may trigger disease exacerbation after medication discontinuation in order to recognize the potential disadvantages of discontinuing treatment in patients who are previously successfully managed on TNF antagonists.