Gastrointestinal adverse events associated with Hedgehog pathway inhibitors: a disproportionality analysis.

Objective: The Hedgehog pathway inhibitors (HPIs) are effectively used to treat basal cell carcinoma (BCC). Despite the benefits, HPIs are reported to cause various gastrointestinal adverse events (GIAEs). The study was conducted to detect possible safety signals of HPIs concerning GIAE through disproportionality analysis.

Methods: A retrospective case/non-case disproportionality analysis was performed in the USFDA Adverse Event Reporting System database using OpenVigil 2.1, a web-based pharmacovigilance tool. All the GIAEs reported due to the HPIs, like vismodegib, sonidegib, and glasdegib, were extracted and analysed. The reporting odds ratio (ROR) > 1 was considered the reporting threshold.

Key findings: The HPIs accounted for 6781 adverse events, with 1196 GIAEs distributed across vismodegib (18.56%), sonidegib (13.89%), and glasdegib (5.39%). A potential safety signal was portrayed with atrophic glossitis [ROR: 181.88 (95% CI: 72.73-454.83)] and ageusia [153.34 (141.20-166.52)] from vismodegib. The study identified concerns of dysgeusia [17.39 (11.72-25.81)] from sonidegib and hepatotoxicity [20.25 (9.02-45.46)] from glasdegib.

Conclusions: HPIs had triggered various types of GIAEs. Liver injuries were a safety concern for the HPI-treated patient, which was not listed by the USFDA. Further researches are needed to confirm these findings.