Systematic Review And Meta Analysis Of Kouyanqing Grauales In The Treatment Of Oral Mucosa Diseases

Objective: To estimate the effectiveness and safety of Kouyanqing grauales and provide the the adequate basis for its clinical application in the treatment of oral mucosa diseases by systematic review and Meta-analysis.Methods: 1. Search strategy Key words: “kouyanqing grauales”, “recurrent aphthous stomatitis”, “recurrent aphthous ulcer”, “herpetic stomatitis”, “oral lichen planus”. Electronic databases: Cochrane Library, Pub Med database, CNKI, VIP, Wanfang database and CBM. These databases were searched from the dates of their establishment to January 2015. Other resource: unpublished data from Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited. 2. Inclusion and exclusion criteria Inclusion criteria:①The included patients meet the diagnostic criteria of RAU, herpetic stomatitis, OLP. ②Intervention measures: interventions for the treatment group are Kouyanqing grauales or combined with other medicine. ③Results measurement: clinical efficacy, ulcer number, ulcer size, pain, ulcer-days, recurrent rate; cooling time, herpes size, herpes number, herpes-days, pain; hyperemia, pain, erosions size. ④Randomized controlled trial and half-randomized controlled studies are included without consideration of the blind and language. Data is complete.Exclusion criteria: ①Results measurement are incongruent. ②Literature is re-published. ③Data is incomplete or mistaken. 3. Quality of studies Two researchers read the literature titles and abstracts independently, then evaluate the literatures according to Jadad score. Eligibility of studies was assessed by researchers. Disagreement was resolved by a third party. 4. Statistical Analysis The Software Rev Man 5.2 provided by Cochrane was used for statistical analysis. Odds ratio(OR) for dichotomous data and weighted mean difference(WMD) for continuous data were calculated and expressed by point estimation and 95% confidence interval. The statistical heterogeneity was assessed by the I2 value, when a value of < 50%, the fixed effect model was used. In view of substantial heterogeneity(I2>50%), the random effect model was used for pooling. Subgroup comparison will be taken to investigate the original of statistical heterogeneity. The potential bias of literature will be shown in the funnel plot.Results: 1. Kouyanqing grauales in treatment of RAU 12 studies(1436 patients) were included in the review of Kouyanqing grauales in treatment of RAU, the results of meta-analyses showed, compared with control group, Kouyanqing grauales was superior in improving RAU(OR=6.87, 95%CI[3.83, 12.34], P < 0.00001). Kouyanqing grauales was superior in marked effect(OR=3.35, 95%CI[2.05, 5.48], P<0.00001). For unrecurrent, Kouyanqing grauales was superior, the difference was significant(OR=4.63, 95%CI[2.19, 9.78], P < 0.0001). For relieving pain, Kouyanqing grauales was superior, but the difference was not significant(OR=0.71, 95%CI[-0.00, 1.42], P=0.05). Though subgroup analysis, difference of control medicine was found to be the original of heterogeneity. 2. Kouyanqing grauales in treatment of herpetic stomatitis 8 studies(918 patients) were included in the review of Kouyanqing grauales in treatment of herpetic stomatitis, the results of meta-analyses showed, compared with control group, Kouyanqing grauales was superior in improving herpetic stomatitis(OR=7.93,95%CI[4.91,12.83],P<0.00001). Kouyanqing grauales was superior in cure rate(OR=4.46,95%CI[2.33,8.50],P<0.00001). For defervescence time, Kouyanqing grauales was superior, the difference was significant(OR=-1.05,95%CI[-1.20,-0.89],P<0.00001). For herpes healing time, Kouyanqing grauales was superior, the difference was significant(OR=-1.39,95%CI[-1.60,-1.19],P<0.00001). 3. Kouyanqing grauales in treatment of OLP 6 studies(388 patients) were included in the review of Kouyanqing grauales in treatment of OLP, the results of meta-analyses showed, compared with control group, Kouyanqing grauales was superior in improving OLP(OR=8.05,95%CI[4.23,15.34],P<0.00001). Kouyanqing grauales was superior in cure rate(OR=3.25,95%CI[2.11,5.00],P<0.00001). For recurrent rate, Kouyanqing grauales was lower, the difference was significant(OR=0.21,95%CI[0.08,0.57],P=0.002). 4. Safety of Kouyanqing grauales in the treatment of oral mucosa diseases 26 studies(1511 patients treated with Kouyanqing grauales) were included in the review, 15 patient were reported with adverse reactions and discontinue after drug withdrawal, the incidence of adverse reactions was 0.99%. Conclusion: Current evidences shows that Kouyanqing grauales is effective and safety in the treatment of oral mucosa diseases. However, for the limited evidence and lower methodological quality of the included studies, this conclusion still needs to be verified with more high-quality RCTs.