Evaluation of the clinical efficacy and safety of topical pirfenidone hydrogel in the management of oral submucous fibrosis:A pilot study

This pilot study aims to evaluate the clinical efficacy and safety of topical 8 percent pirfenidone hydrogel in the management of Oral Submucous Fibrosis (OSMF), a chronic, progressive, and potentially malignant oral disorder with no definitive curative treatment. OSMF is primarily driven by areca nut–induced inflammation and dysregulated collagen metabolism mediated by transforming growth factor-beta (TGF-beta). Pirfenidone, an FDA-approved antifibrotic drug for idiopathic pulmonary fibrosis, targets fibrosis at a molecular level by downregulating TGF-beta signaling, reducing collagen synthesis, fibroblast proliferation, inflammation, oxidative stress, and abnormal extracellular matrix deposition. The topical, muco-adhesive gel formulation is designed to deliver high local drug concentrations directly to affected oral tissues while minimizing systemic exposure and adverse effects.

The study is designed as a prospective pilot trial enrolling 30 clinically diagnosed OSMF patients, with outcomes assessed over a 12-week period. Primary efficacy is measured by improvement in interincisal mouth opening, while secondary outcomes include reduction in burning sensation and pain, improvement in cheek flexibility, mucosal blanching, fibrotic bands, and overall quality of life using validated scales (VAS and UW-QOL). Safety will be assessed through monitoring of local and systemic adverse effects, along with plasma pirfenidone levels to evaluate systemic absorption. By targeting the core fibrotic pathway rather than providing only symptomatic relief, this study seeks to establish preliminary evidence for topical pirfenidone as a safe, non-invasive, and disease-modifying therapeutic option for OSMF, paving the way for larger controlled clinical trials.