Department of Pharmaceutical Care, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University, Chiang Mai, Thailand.
JAMA Dermatol. 2021 Nov 1;157(11):1316-1327. doi: 10.1001/jamadermatol.2021.3237.
The comparative benefits and harms of all available treatments for H1 antihistamine-refractory chronic spontaneous urticaria (CSU) have not been established.
To evaluate different treatment effects of pharmacologic treatments among patients with H1 antihistamine-refractory CSU.
Searches were conducted of MEDLINE, Embase, PubMed, Cochrane Library, Web of Science, Scopus, and CINAHL from inception to April 19, 2021, with no language restrictions. Gray literature from Google Scholar, ongoing trial registers, and preprint reports was added to the searches of electronic databases.
Randomized clinical trials using validated measurement tools that investigated the benefits and harms of pharmacologic treatments among adolescent or adult patients with CSU who had an inadequate response to H1 antihistamines were screened for inclusion independently by 2 investigators.
Two investigators independently extracted study data according to the predefined list of interests. A random-effects model was used to calculate the network estimates reported as standardized mean differences and odds ratios with corresponding 95% CIs.
The primary outcomes that reflect the patient's perspective included changes in urticaria symptoms from baseline and unacceptability of treatment (all-cause dropouts).
Twenty-three randomized clinical trials with 2480 participants that compared 18 different interventions or dosages and placebo were included. The standardized mean differences for change in urticaria symptoms were -1.05 (95% CI, -1.37 to -0.73) for ligelizumab, 72 mg; -1.07 (95% CI, -1.39 to -0.75) for ligelizumab, 240 mg; -0.77 (95% CI, -0.91 to -0.63) for omalizumab, 300 mg; and -0.59 (95% CI, -1.10 to -0.08) for omalizumab, 600 mg. No significant differences in treatment unacceptability were observed. With respect to benefits and harms, the network estimates illustrated that the most efficacious treatments were achieved with ligelizumab, 72 or 240 mg (large beneficial effect) and omalizumab, 300 or 600 mg (moderate beneficial effect).
The findings in this meta-analysis suggest that the biologic agents ligelizumab, 72 or 240 mg, and omalizumab, 300 or 600 mg, can be recommended as effective treatments for patients with CSU who have had an inadequate response to H1 antihistamines. Head-to-head trials with high methodologic quality and harmonized design and outcome definitions are needed to help inform subsequent international guidelines for the management of CSU.
尚未确定所有可用的 H1 抗组胺药难治性慢性自发性荨麻疹（CSU）治疗方法的比较益处和危害。
评估 H1 抗组胺药难治性 CSU 患者中药物治疗的不同治疗效果。
从开始到 2021 年 4 月 19 日，对 MEDLINE、Embase、PubMed、Cochrane 图书馆、Web of Science、Scopus 和 CINAHL 进行了检索，没有语言限制。从电子数据库的搜索中添加了来自 Google Scholar、正在进行的试验登记册和预印本报告的灰色文献。
使用验证过的测量工具的随机临床试验，调查了 H1 抗组胺药反应不足的青少年或成年 CSU 患者中药物治疗的益处和危害，由 2 名调查员独立筛选纳入。
根据预先确定的利益清单，2 名调查员独立提取研究数据。使用随机效应模型计算网络估计值，以标准化均数差值和优势比表示，并附有相应的 95%置信区间。
反映患者视角的主要结果包括从基线开始的荨麻疹症状变化和治疗不可接受性（所有原因的脱落）。
纳入了 23 项随机临床试验，涉及 2480 名参与者，比较了 18 种不同的干预措施或剂量与安慰剂。利格珠单抗 72mg 的荨麻疹症状变化的标准化均数差值为-1.05（95%CI，-1.37 至-0.73）；利格珠单抗 240mg 的标准化均数差值为-1.07（95%CI，-1.39 至-0.75）；奥马珠单抗 300mg 的标准化均数差值为-0.77（95%CI，-0.91 至-0.63）；奥马珠单抗 600mg 的标准化均数差值为-0.59（95%CI，-1.10 至-0.08）。未观察到治疗不可接受性的显著差异。就益处和危害而言，网络估计表明，最有效的治疗方法是利格珠单抗 72 或 240mg（大有益处）和奥马珠单抗 300 或 600mg（中等有益处）。
这项荟萃分析的结果表明，生物制剂利格珠单抗 72 或 240mg 和奥马珠单抗 300 或 600mg 可被推荐为 H1 抗组胺药反应不足的 CSU 患者的有效治疗方法。需要具有较高方法学质量和协调设计和结果定义的头对头试验，以帮助为 CSU 的管理提供后续国际指南。
