Three Second-generation Antihistamine Treatment Of Allergic Rhinitis And Urticaria, Effectiveness And Safety Evaluation

Background: Hypersensitivity disease has became global disease which effects human health seriously in 21st century. Allergic rhinitis and urticaria both are typical heypersensitivity disease, and belong to I type allergy which relate histamine closely. So antihistamines are used to treating hypersensitivity disease extensively, and the second-generation antihistamines have gained widespread acceptance and developed very quickly because of their positive efficacy and reduced side effects relative to first-generation antihistamines. Loratadine, cetirizine and mizolastine are the largest sales among antihistamines in Chinese market. But lots of studies' results are not equal about the efficacy and safety of these medicines.Objective: To assess the clinical efficacy, safety, cost-effectiveness and acceptability of lortadine, cetrizine and mizolastine for patients with allergic rhinitis or urticaria by using systematic review of evidence, and to provide evidence for healthcare decision making and rational drug use.Methods: We seached Cochrane library, Embase. com (including MEDLINE和EMBASE) and Chinese Biomedical Database, and screened the references of eligible studies, all the searches were updated March, 2007. Two reviewers independently screened the studies for eligibility, evaluted the quality and extracted the data from eligible studies, with confirmation of cross-check. And different opinions were consulted by discussion. Meta analysis and the method of describing are used to assess the efficacy of these three medcines. Meta analysis was done by Revman 4.2.8. We used chi-square test to assess heterogeneity among studies. Without heterogeneity, we used fixed effect model meta anlysis to pool the studies. If there is therogeneity, we anlysised the reasons firstly and used subgroup analysis, sensitivity analysis and random effect model meta analysis to deal with. Only the method of describing was used to assess the safety.Results: A total of 22 randomized controlled trials were inclued in study of clinical effects for allergic rhinitis, and most of them were high in quality, while those in Chinese are low. There are not statistics differents between loratadine and placebo in improving total symptom score, single symptom score and satisfaction rate for patients with seasonal and personal allergic rhinitis, only in improving patients'quality-of-life score, loratadine is significantly better than placebo for allergic rhinitis (WMD=0.18,95%CI=0.02-0.33, P=0.02). While cetirizine and mizolastine both are significantly better than placebo in improving all scores of seasonal and personal allergic rhinitis, (WMD=1.6, 95%CI=1.54～1.66, P＜0.0001) and (WMD=1.94, 95%CI=1.01～2.88, P＜0.0001). And cetirizine is significantly beteer than loratadine in all aspects. While there isn't significant difference between mizolastine and cetirizine in improving total symptom scores of all patients with allergic rhintis. 22 randomized controlled trials were included in the clinical effect study for urticaria, and most of them are Chinese and low in quality. The rate of effective is significantly higher in loratadine, cetirizine and mizolastine, compared to placebo for chronic urticaria. Mizolastine is significantly better than loratadine for acute urticaria, while is equal with loratadine for chronic urticaria. And only the rate of effectiveness of mizolastine is significantly higher than cetirizine's for chronic urticaria (RR=1.09, 95%CI=1.04～1.15, P=0.0006), there is not statistics difference between mizolastine and cetirizine in other aspects. Study of safety included 46 RCTs and 26 case reports and adverse reaction report of WHO. We found that the rate of common adverse reaction in loratadine, cetrizine, mizolastine and placebo is 21.8%,20.9%,23.2% and 25.7% respectively, they are generally similar and there is not statistic difference. WHO reported that serious adverse reaction occoured more frequently with loratading (405 cases) than cetrizine (36 cases) in 1986-1996. And 15 patients with loratadine, 10 with cetirizine and 1 with mizolastine have occurred serious adverse reaction in China since 1997.One economic study reported that cetirizine made in china is better than zyrtec made in Belgium for acute and chronic urticacir by using cost-effectiveness analysis; Another study used cost-minimization analysis and cost-effectiveness analysis to assess these three medcines' cost and efficacy, and the result displayed that cetirizine is the best for chronic urticacir.Conclusion: For allergic rhinitis, both cetrizine and mizolastine are significantly better than placebo, while loratadine is equal to placebo nearly; and cetirizine is better than loratadine, and is equal to mizolastine. All of three kinds medicine are significantly better than placebo for chronic urticaria; mizolastine is better than loratadine for acute urticaria, and better than cetirizine for chronic urticaria. The rate of common adverse reaction of three kinds medicines are equal nearly, incidence of serious adverse reaction of loratadine is more than the others, and at least with mizolastine.