Clinical effectiveness and safety of total glucosides of paeony as an immunomodulator in patients with refractory oral lichen planus: A multicenter, pragmatic, randomized controlled trial.

BACKGROUND

Refractory oral lichen planus (OLP) poses a treatment challenge due to its chronic nature, symptoms, and potential for malignant transformation. Total glucosides of paeony (TGP), a botanical immunomodulator that targets NF-κB and Th17 pathways, have demonstrated promise in managing OLP. However, robust clinical evidence from real-world settings remains lacking.

PURPOSE: This study aimed to assess the effectiveness and safety of TGP as an add-on therapy for patients with symptomatic refractory OLP in a real-world clinical trial setting.

STUDY

DESIGN

This multicenter, pragmatic, randomized, active-controlled trial (Chinese Clinical Trial Registry: ChiCTR-IPR-16,010,156) enrolled 448 adults with symptomatic refractory OLP from five Chinese centers between January 2017 and December 2020. The pragmatic design assessed TGP under real-world conditions.

METHODS

Participants were randomly assigned in a 1:1 ratio to receive basic therapy (tapering prednisone from 15 mg to 5 mg over 4 weeks plus standardized oral hygiene; n = 222) or basic therapy plus TGP (0.6 g three times daily for 12 months; n = 226). The primary endpoint was the time from randomization to complete response (CR), defined as reducing the VAS pain score and Thongprasom sign score to 0 or 1 (or to 0 if the baseline score was 1).

RESULTS

The TGP group demonstrated significantly faster achievement of CR and higher CR rates compared to controls (53.9% vs. 34.4%; hazard ratio [HR] 2.07, 95% confidence interval [CI] 1.52-2.82; p < 0.0001) and better overall response rates at 12 months (70.6% vs. 44.4%; odds ratio [OR] 2.99; 95% CI 2.01-4.44; p < 0.0001). Patients receiving TGP also experienced greater improvements in sleep quality (PSQI responder rate: HR 1.49, p = 0.038). The safety analysis primarily showed mild adverse events, with a higher incidence of diarrhea in the TGP group (5.5% vs. 0.9%), but no severe events or treatment discontinuations.

CONCLUSION

As an add-on therapy, TGP significantly improved clinical outcomes in refractory OLP in a real-world setting, demonstrating immunomodulatory effects and a favorable safety profile. These pragmatic trial results support TGP as a promising and effective long-term add-on therapy for the long-term management of this potentially malignant disorder.