Evidence-based Evaluation Of Traditional Chinese Medicine In The Treatment Of Gout And The Efficacy Evaluation Of Qingpeng Ointment In The Intervention Of Acute Gout Attack

BackgroundGout is a crystal-related arthritis caused by elevated serum uric acid,and its prevalence and disease burden are rising year by year.Both Chinese medicine and ethnic medicine are important parts of traditional Chinese medicine system,and both of them can be used to treat gout.With the development and popularization of evidence-based medicine,there are more clinical trials with higher methodological quality evaluating the efficacy and safety of Chinese medicine for gout being conducted and published in recent years.However,there is no systematic review that comprehensively synthesized the clinical study evidence in the last eight years.Traditional Tibetan medicine is one of the four major ethnic medicines in China.Among many Tibetan medicines,Qingpeng ointment is safe and convenient to use.and can relieve joint symptoms of gout.There is no double-blind,randomized controlled trials that clearly evaluate the efficacy of Qingpeng ointment for gouty arthritis.Qualitative research can explore the cognition,attitude,and experience of patients.At present,there is no qualitative research that explored the cognition and attitude of patients with gout towards Chinese medicine.ObjectivesTo comprehensively evaluate the efficacy and safety of Chinese medicine for gout.To clearly evaluate the efficacy and safety of Qingpeng ointment for acute gouty arthritis.To explore the cognition,attitude and experience of patients with acute gouty arthritis to Qingpeng ointment,and to explore the cognition and attitude of patients with gout towards Chinese medicine.MethodsStudy 1:Seven major Chinese and English databases were systematically searched.Randomized controlled trials that met the following criteria were included:Participants were patients diagnosed with gout;Interventions were Chinese medicine:Treatment for control group was no treatment/placebo/conventional western medicine;At least one of the primary(joint pain.joint function,quality of life,recurrence)or secondary(joint swelling,C-reactive protein.serum uric acid,adverse events)outcomes was reported:Appropriate randomization method was used and reported.Data in included studies was extracted,and the methodological quality of included studies was evaluated.Data from studies with high homogeneity was synthesized by meta-analysis.Data not suitable for meta-analysis was described qualitatively.Study 2:A multicenter,double-blind,randomized controlled trial was designed and c onducted.A total of 206 patients diagnosed with acute gouty arthritis were randomly assigned to treatment group and control group.Patients in treatment group were treated with Qingpeng ointment.and patients in control group were treated with placebo ointment.2 times a day,for consecutive 7 days.Patients in both groups were given diclofenac sodium sustained-release tablets as rescue medicine.Patients were suggested to take the rescue medicine only when joint pain was intolerable,and visual analogue scale(VAS)score of joint pain was ≥7 points.Primary outcomes were VAS score of joint pain and degree of joint swelling(VAS score of joint swelling,width and thickness of affected joint).Secondary outcomes were score of joint function,score of skin color,C-reactive protein,serum uric acid,and usage amount of rescue medicine.Safety outcomes included vital signs and adverse events.Study 3:One-to-one,semi-structured qualitative interviews were conducted with several participants from the clinical trial of Study 2.The interview was related to patients’ cognition,attitude and expectation of Qingpeng ointment for treating acute gouty arthritis,as well as the treatment situation and experience during the clinical trial.The interview was also related to patients’cognition and attitude towards Chinese medicine for treating gout,and patients’ treatment needs and expectations of Chinese medicine.The interview process was recorded.Thematic analysis method was used for analysis.ResultsStudy 1:The literature search identified 5947 studies.After screening.94 randomized controlled trials were finally included.The overall methodological quality of the included studies was limited.Due to the heterogeneity between included studies,only data from a few studies with high homogeneity were synthesized by meta-analysis.Among the studies comparing oral Chinese medicine with western medicine,22 studies reported serum uric acid,of which 16 showed that Chinese medicine was more effective than western medicine;15 studies reported C-reactive protein,of which 8 showed that Chinese medicine was more effective than western medicine.Among the studies comparing oral Chinese medicine combined with western medicine to oral western medicine alone,44 studies reported serum uric acid,of which 35 showed that the combination of Chinese and western medicine was more effective than western medicine alone;33 studies reported C-reactive protein,of which 28 showed that the combination of Chinese and western medicine was more effective than western medicine alone;34 studies reported joint pain,of which 32 showed that the combination of Chinese and western medicine was more effective than western medicine alone:9 studies reported joint mobility.7 of which showed that the combination of Chinese and western medicine was more effective than western medicine alone;11 studies reported joint swelling,of which 10 showed that the combination of Chinese and western medicine was more effective than western medicine alone.Among the studies of using Chinese medicine externally,6 studies added the external use of Chinese medicine to the oral use of western medicine,and 4 of them showed that,in terms of relieving joint symptoms,external Chinese medicine combined with oral western medicine was more effective than oral western medicine alone.Quality of life was reported in 4 studies,3 of which showed that the combination of Chinese and western medicine was more effective than western medicine alone.Meta-analysis showed that,in terms of lowering serum uric acid,Chinese medicine based on Simiao Decoction was more effective than non-steroidal anti-inflammatory drugs(MD=-33.57 μmol/L,95%CI-51.66 to-15.49;P=0.0003;3 trials,180 patients);Chinese medicine based on Guizhi Shaoyao Zhimu Decoction combined with urate-lowering medicine was more effective than urate-lowering medicine alone(MD=-39.27 μmol/L.95%CI-44.70 to-33.84:P<0.00001;2 trials.151 patients);in terms of lowering C-reactive protein.Chinese medicine based on Simiao Decoction was more effective than non-steroidal anti-inflammatory drugs(MD=-2.74 mg/L,95%CI-4.49 to-0.99;P=0.002:2 trials.140 patients).In terms of safety,adverse events occurred in Chinese medicine group was significantly less than that in the western medicine group.Study 2:A total of 206 patients from 3 hospitals were recruited,of which 3 were mis-included.and 188 completed the trial process.The joint pain VAS score of patients in both groups decreased after treatment,but there was no statistical difference between the efficacy of the 2 groups(P>0.05).The joint swelling VAS score of patients in both groups decreased after treatment,but there was no statistical difference between the efficacy of the 2 groups(P>0.05).The width and thickness of affected joints in both groups decreased after treatment,but there was no statistical difference between the efficacy of the 2 groups(P>0.05).The joint function score of patients in both groups decreased after treatment,and the difference between the 2 groups was significant(P=0.013).The skin color score of patients in both groups decreased after treatment,but there was no statistical difference between the efficacy of the 2 groups(P>0.05).The C-reactive protein of patients in both groups decreased after treatment,but there was no statistical difference between the efficacy of the 2 groups(P>0.05).The serum uric acid of patients in both groups decreased after treatment,but there was no statistical difference between efficacy of the 2 groups(P>0.05).There was no statistical difference in the usage amount of rescue medicine between the 2 groups(P>0.05).Four patients in the treatment group and 1 patient in the control group developed adverse events,mainly manifestated as skin irritation.All adverse events were cured after drug discontinuation or treatment.Study 3:A total of 20 patients were interviewed.The results showed that,recommended by doctors or other patients,considering trying to treat gouty arthritis with Qingpeng ointment was the main motivation for patients to participate in the trial.The treatment expectations of patients were primarily to relieve joint pain and swelling.Some patients had poor compliance during the trial process,for example,increased the times of using ointment on their own,and did not take the rescue medicine according to the study protocol.Patients had different experiences and satisfaction with the treatment.Some of the patients in both groups were satisfied with the efficacy,and some in both groups were not satisfied.The results of the quantitative study and the qualitative study were integrated,and the results showed that,there was no significant difference in the efficacy of Qingpeng ointment and placebo ointment in relieving joint symptoms.Information from the qualitative interviews further strengthened the interpretation of the results of clinical trial.Suggestions for improving the trial were summarized,such as strengthening the follow-up of patients to improve patient compliance.Patients who chose Chinese medicine to treat gout mainly focused on its conditioning effect and safety.Patients believed that Chinese medicine could safely regulate the internal metabolic balance of the body,fundamentally treat the disease,and achieve long-term therapeutic effects.Patients would also choose Chinese medicine to treat gout based on previous habits or treatment experience,and the recommendation of others.Patients who did not choose Chinese medicine to treat gout mainly thought that Chinese medicine relieved joint symptoms too slowly,or were affected by previous unsatisfactory treatment experience.Some patients did not choose Chinese medicine because of the troublesome use and poor taste of Chinese medicine decoction,or lacking cognition of Chinese medicine for treating gout.Some patients believed that the combination of Chinese medicine and western medicine would achieve better therapeutic effect.Conclusions1.Chinese medicine has advantages in lowering uric acid and C-reactive protein in the treatment of gout;the efficacy of oral Chinese medicine alone,or oral Chinese medicine combined with western medicine is mostly better than that of western medicine alone.Chinese medicine has some effect in relieving joint pain and swelling,and improving joint function;the efficacy of oral Chinese medicine combined with western medicine is mostly better than that of oral western medicine alone:compared with oral western medicine alone.the addition of external Chinese medicine can also enhance the efficacy.Chinese medicine also has some effect in improving quality of life:compared with western medicine alone,the addition of Chinese medicine can enhance the efficacy.2.For patients with acute gouty arthritis,in terms of improving joint function,Qingpeng ointment is slightly more effective than placebo ointment.In terms of relieving joint pain,swelling and redness,there is no significant difference in the efficacy between Qingpeng ointment and placebo ointment.Qingpeng ointment is safe for treating acute gouty arthritis.Information from the qualitative interview further strengthens the interpretation of the results of the clinical trial.Suggestions for improving the trial include strengthening the follow-up of patients to improve patient compliance.3.The expectation of patients with gout for Chinese medicine is to safely regulate the internal metabolic balance of the body,fundamentally treat the disease,and achieve long-term therapeutic effects.The motivation of patients to choose Chinese medicine to treat gout also includes previous habits,previous treatment experience,and the recommendations from others.Patients think that the deficiency of Chinese medicine in the treatment of gout mainly lies in the slow relief of joint symptoms.Patients believe that the combination of Chinese medicine and western medicine can achieve a better therapeutic effect in the treatment of gout.