Mitigation of Mouth Opening in Oral Submucous Fibrosis with Nutraceutical Products: A Network Meta-Analysis

Oral submucous fibrosis (OSF) is associated with habitual use of areca nut. Several nonsurgical interventions for OSF have been used, with increasing predilection to try plant-based products. The objective of the present study is to investigate the efficacy of nutraceutical products (NPs) and other classes of nonsurgical interventions in OSF management using the network meta-analysis (NMA) approach. After registering with PROSPERO, the present study systematically searched for relevant studies in databases. PICO framework was used to identify studies relevant to evaluate the effectiveness of NPs and other classes of interventions. Standard NMA tools were used to assess the quality of the included studies and perform analysis. A total of 51 studies were included for final analysis with 53 trials. The primary outcome of identified studies was the mean difference (MD) in mouth opening (MO) expressed as mean (95% confidence interval). There were 16 interventions including placebo involving 3850 patients. The highest MD is 10.14 (4.38-15.89) with steroids with/without spreading factor (SSF) with ultrasonography (USG), followed by 9.87 (2.96-16.78) with SSF and NP-systemic and USG application, while the least is 1.43 (-4.31 to 7.18) SSF (8.04%). The probability of placebo being the most effective intervention in MO is the highest (93.91%), followed by exercise (81.50%), as evidenced by Surface Under the Cumulative Ranking Curve (SUCRA) and litmus rank-o-gram. This NMA results, within its limitation, showed that several NP outcomes are statistically superior to placebo in improving the MO, but as a class of drugs, none of the classes exhibited supremacy over others, especially to placebo. The result of this NMA indicates that none of classes of non-surgical treatment, especially NPs, have no distinct advantage in mitigation MO in OSF treatment.