Comparative Efficacy of Interventions for the Management of Oral Submucous Fibrosis: A Systematic Review and Network Meta-Analysis

Abstract

Introduction: Oral submucous fibrosis (OSMF) is a chronic premalignant condition and is characterized by fibroblastic change of lamina propria and stiffness of oral mucosa. Though there are several treatment options available, the best agent is not yet identified. This study assessed the comparative efficacy and safety of medical interventions in the management of OSMF. Methods: A systematic review was performed to identify randomized controlled trials (RCTs) that compared the efficacy of interventions for OSMF with each other, or placebo. A network meta-analysis was performed, and the interventions were ranked according to their efficacy based on the surface under the cumulative ranking. (PROSPERO Registration no: CRD42021255094). Results: Thirty-two RCTs comprising 2063 patients were eligible for quantitative analysis. In terms of therapeutic efficacy in the improvement of mouth opening Oxitard, a herbal formulation was ranked as the most efficacious agent, [MD, 10.29 (95%CI 6.34–14.25)] followed by combination therapy of Lycopene with corticosteroids and hyaluronidase [MD, 7.07 (95%CI 1.82–12.31)]. For improvement of burning sensation aloe vera was ranked first [MD, 6.14 (95%CI 4.58–7.70)] followed by corticosteroids with antioxidants [MD, 6.13 (95%CI 4.12–8.14)] and corticosteroids in combination with hyaluronidase with antioxidants [MD, 5.95 (95%CI 3.79–8.11)]. In terms of safety, most of the drugs were reported to cause mild adverse effects only. Significant inconsistencies could be identified in the analysis for both the outcomes assessed and were further explored. Conclusions: Our study highlighted the potential efficacy of several agents over placebo in the improvement of mouth opening and burning sensation in OSMF patients. However, the RCTs lacked methodological soundness. Well-designed studies with a larger number of participants with a rigorous randomization process and stringent methodology are recommended to strengthen the results obtained, which may help to construct a clinical guideline for OSMF management.

Polyphenol-based targeted therapy for oral submucous fibrosis

“…The intralesional injection of corticosteroids suppresses TGF-β1 and forms the mainstay in the treatment of OSF (Shih et al 2019 ). Nonetheless, none of the therapies have resulted in the successful treatment of OSF apart from rendering symptomatic relief to patients (Gopinath et al 2022 ). The standard treatment, corticosteroid injection reported side effects with higher chances of infection at the site of injection and systemic side effects such as adrenal insufficiency, edema, osteonecrosis, osteoporosis, myopathies and central serous chorioretinopathy, Hence, there is a need to identify an effective strategy for the treatment of OSF, which can be an alternative to the currently available treatment and provide symptomatic relief.…”

Comparative Efficacy of Oxitard Capsules and Immusante Tablets in Early Stages of Oral Submucous Fibrosis - A Randomized Controlled Trial

“…Various studies included in the review did state that antioxidants were effective in managing OSMF, but the heterogeneity across the studies and the limited number of studies reported in the literature does not permit firm conclusions 12 . In contrast, another systematic review and network meta-analysis reported that Oxitard was the most effective compared to all other interventions in improving mouth opening among OSMF patients 25 . Though Oxitard has been shown to be effective in various studies, it also has some associated side effects.…”

“…A prospective randomized controlled trial demonstrated significant improvement in the objective criteria like mouth opening, tongue protrusion, and relief from perioral fibrotic bands. Further, subjective criteria like a burning sensation in the mouth and difficulty in speech also recorded significant improvements 25 .…”

Drug treatment for oral submucous fibrosis: an update

“…In a network meta-analysis comparing the efficacy of different treatment interventions for OSF [80], most interventions were found to be superior to placebo in improving clinical symptoms, such as MMO and BS. Oxitard is superior to other interventions in improving MMO, aloe vera is superior in relieving BS, and lycopene has the lowest propensity for side effects and can be considered the best safety agent.…”