| Part Ⅰ: A meta-analysis of the efficacy and safety of LABA/LAMA versus LAMA and LABA/ICS in the treatment of COPD.Objective:To evaluate the efficacy and safety of long-acting β2agonist/long acting muscarinic antagonist(LABA/LAMA)fixed dose combination compared with LAMA and β2agonist/inhaled glucocorticoid(LABA/ICS)fixed dose combination in maintenance treatment of moderate to severe chronic obstructive pulmonary disease(COPD).Methods: Through the search of PUBMED,MEDLINE,EMBASE and CENTRAL database,all randomized controlled trials of LABA/LAMA combined preparations compared with LAMA and LABA/ICS drugs in the treatment of chronic obstructive pulmonary disease were screened.The data were extracted and the quality of the literature was evaluated using the risk bias criteria listed in the systematic review of intervention treatment in the Cochrane manual.Meta analysis was carried out by Rev Man5.3 software.Results:A total of 35 articles include 43 studies(N=28391).(1)Compared with LAMA,LABA/LAMA combination could effectively increase the peak value of FEV1 in the first second and the valley value and the deep inspiratory capacity of the patient(P<0.05).It can significantly reduce the score of SGRQ,effectively increase TDI score,and significantly reduce the frequency of use of rescue drugs(P<0.05).There was significant difference in cough(P<0.05)between LABA/LAMA compound preparation and LAMA treatment,but there was no significant difference in the incidence of nasopharyngitis,cardiovascular and disease exacerbation between the two groups.(2)Compared with LABA/ICS,LABA/LAMA combination could effectively increase the peak value of forced expiratory in the first second and the valley value(P<0.05).It could increase the index of transitional dyspnea TDI score and reduce the frequency of use of rescue drugs(P<0.05),but there was no significant difference in the score of SGRQ and the CAT score of COPD.Compared with LABA/ICS treatment,LABA/LAMA compound preparation could significantly reduce the incidence of pneumonia(RR=0.64,P<0.05)and upper respiratory tract infection(RR=0.81,P<0.05),but there was no significant difference in the occurrence of nasopharyngitis and disease exacerbation between the two groups.Conclusion:1.Compared with LAMA groups,LABA/LAMA combination can effectively improve the pulmonary function and relieve symptoms of patients.But can not effectively reduce the incidence of disease exacerbation.After treatment,the possibility of mild increase of adverse reactions such as cough is high.2.Compared with the LABA/ICS group,LABA/LAMA combination can effectively improve the pulmonary function of the patients.There was no significant difference between the two types of drugs in relieve symptoms and reducing the incidence of disease exacerbation.After treatment,LABA/ICS drugs had a higher risk of pneumonia and upper respiratory tract infection.PART Ⅱ: A network meta-analysis of the efficacy and safety of LABA/LAMA,LAMA,LABA/ICS drugs in the treatment of stable COPDObjective: To evaluate five LABA/LAMA combinations(indacaterol/glycopyrronium,tiotropium/olodaterol,umeclidinium/vilanterol,glycopyrronium/formoterol,aclidinium/formoterol)efficacy and safety between(LAMA)and salmeterol(LABA/ICS)in the treatment of COPD.Methods: Through the search of PUBMED,MEDLINE,EMBASE,CENTRAL,CNKI and WANFANG database,all randomized controlled trials of LABA/LAMA compound,tiotropium and salmeterol/fluticasone in the treatment of COPD were selected.The data were extracted and the quality of the literature was evaluated using the risk bias criteria listed in the systematic review of intervention treatment in the Cochrane manual.The network meta analysis was carried out by Stata16 software.Results: A total of 48 articles include 52 studies(N=45854).Compared with placebo,there were significant differences in through FEV1,SGRQ,TDI score between placebo and placebo.Compared with other drugs,there was significant difference in the increase of through FEV1 between indacaterol/glycopyrronium and umeclidinium/vilanterol(P<0.05).Salmeterol/fluticasone50/500 ug compared with placebo and indacaterol/glycopyrroniumin the incidence of pneumonia(P<0.05)has significant difference.There was no significant difference among different interventions in upper respiratory tract infection,cough and exacerbation.In addition,indacaterol/glycopyrronium ranked first in terms of SUCRA in terms of improving lung function and relieving symptoms.Conclusion: Among the different combinations of LABA/LAMA,umeclidinium/vilanterol and indacaterol/glycopyrronium have outstanding advantages over other drugs in improving lung function in patients with moderate to severe COPD.Therefore,on the basis of single drug can not control the disease,it can be used as the first choice for patients with moderate to severe COPD.Among them,indacaterol/glycopyrronium bromide has the highest possibility of having the best therapeutic effect among all the contrastive drugs,and there are no obvious adverse reactions.In addition,salmeterol/fluticasone(50/500μg)had a higher risk of pneumonia in patients with moderate to severe COPD during long-term maintenance treatment,while salmeterol fluticasone(50/250μg)had no significant incidence of pneumonia.Part Ⅲ: Cost-effectiveness of long-term maintenance therapy in patients with stable COPD by Markov modelObjective: To evaluate the advantages and disadvantages of umeclidinium/vilanterol,salmeterol/fluticasone and tiotropium in the treatment of moderate to severe stable chronic obstructive pulmonary disease(COPD)from the point of view of macroeconomics.Methods: A Markov model was constructed according to the state development of COPD disease in large randomized controlled clinical trials.the cycle was simulated for 3 months and 3 years,with a discount rate of 3%.Treeage2011 software was used to calculate the incremental cost-effectiveness ratio and carry out roll back analysis,cohort simulation,Monte Carlo simulation and single factor sensitivity analysis.Results: According to the cohort simulation results of Markov model,the incremental effect of tiotropium bromide,salmeterol/fluticasone 50/250μg and salmeterol/fluticasone 50/500μg decreased by 0.002565,0.00085 and 0.001077,respectively.Cumulative per capita costs increased by ￥2075.1669,￥283.2804 and ￥4044.3602,respectively.ICER decreased by ￥809022.3847,￥332374.5635 and ￥3756788.02156,respectively.umeclidinium/vilanterol has obvious economic advantages.Probability sensitivity analysis and single factor sensitivity analysis show that the cost-effectiveness result is stable.Conclusion: From the perspective of social medical payment,in the three-year treatment,for stable low-risk moderate to severe COPD patients,umeclidinium/vilanterol has the best cost-effectiveness ratio,indicating that the drug has the highest output effect and the lowest total cost,and the result is still robust within the range of 25% fluctuation in the cost of each drug.The side shows that as a new drug in the market in China,its current price is quite reasonable,which is a great blessing for patients with COPD. |
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