Ibuprofen gargle for quality of life and pain improvement in oral lichen planus: randomized crossover and long-term extension phase II study

Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease of the oral mucosa that frequently causes erosive lesions accompanied by pain, thereby impairing the patient’s ability to eat and drink and their overall quality of life (QOL). Current guidelines recommend topical corticosteroids as first-line treatments; however, their efficacy is limited for pain relief, and long-term safety remains a concern. Nonsteroidal anti-inflammatory drug mouthrinse formulations can deliver high local drug concentrations to the symptomatic mucosa with minimal systemic exposure. This study evaluated the short- and long-term safety and efficacy of ibuprofen gargling in patients with painful OLP. We conducted a randomized, double-blind, placebo-controlled crossover study (Days 1–7), followed by a 6-month open-label long-term extension (LTE) study (Days 8–176). Patients with OLP and baseline oral pain of ≥ 20 mm on a 100-mm visual analog scale (VAS) were enrolled. The LTE study’s primary endpoint was safety, and secondary endpoints included changes in the VAS in resting oral pain and oral health-related QOL, which was measured using the Patient-Reported Oral Mucositis Symptom (PROMS) scale. The crossover study enrolled 24 patients, and 18 patients continued the LTE study. No serious adverse events were observed. One patient discontinued treatment because of grade 2 oral pain, while the remaining patients tolerated long-term treatment exhibiting stable laboratory values. During the LTE study, ibuprofen gargling was associated with significant improvements in several PROMS domains. The most pronounced effects were observed in the dietary domains, including eating restriction (βday = − 0.083, p < 0.001) and difficulty eating hard foods (βday = − 0.067, p < 0.001). Modest but significant improvements were observed for mouth pain (βday = − 0.038, p = 0.029), difficulty eating soft foods (βday = − 0.021, p < 0.001), swallowing (βday = − 0.007, p < 0.001), and drinking (βday = − 0.006, p = 0.043). A 6-month regimen of ibuprofen gargling may be safe and associated with modest and gradual improvements in pain and oral function-related QOL in patients with OLP. Further confirmatory study is needed to confirm the potential therapeutic role of ibuprofen gargling. The Registry of Clinical Trials; jRCTs051220009 and jRCTs051220010, date of registration: 22 April 2022.