Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.
Efficacy, dose reduction, and resistance to high-dose fluticasone in patients with eosinophilic esophagitis.
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DOI：
10.1053/j.gastro.2014.04.019
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发表时间：
2014-08
期刊：
影响因子：
29.4
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
Butz BK;Wen T;Gleich GJ;Furuta GT;Spergel J;King E;Kramer RE;Collins MH;Stucke E;Mangeot C;Jackson WD;O'Gorman M;Abonia JP;Pentiuk S;Putnam PE;Rothenberg ME
我们评估了大剂量口服丙酸氟替卡松(FP)和减少剂量治疗嗜酸性食管炎(EoE)的有效性和安全性，并分析了食道转录以确定机制。我们进行了一项随机、多点、双盲、安慰剂对照试验，每天对3-30岁EoE活动期的参与者进行1760微克FP。28名参与者接受了FP，14名接受了安慰剂。3个月后，接受FP的完全缓解(CR)的参与者每天接受880微克FP，而FP组或安慰剂组的非CR组的参与者分别继续或开始每天1760微克FP，持续3个月。主要终点是CR的组织学证据。次要终点为部分缓解(PR)、症状、顺应性、食道基因表达、食道嗜酸粒细胞计数以及临床特征与FP反应性的关系。3个月后，服用FP的受试者和没有服用安慰剂的受试者中有65%处于CR(P=0.0001)；服用FP的受试者中有12%的人处于PR中，而服用安慰剂的受试者中有8%的人处于PR中。在FP组，每日剂量减少50%后，73%的受试者仍处于CR，20%的受试者仍处于PR状态。在FP耐药的参与者中延长FP治疗并未导致缓解。FP降低了胃灼热的严重程度(P=.041)。依从性、年龄、性别、特应性状态或拟人化特征与FP的反应无关。FP应答者的食道组织中的基因表达模式与没有EoE的患者相似；有证据表明，在FP无效的受试者中，类固醇信号不同。每天服用大剂量FP可使65%-77%的EoE患者在3个月后组织学缓解。对于最初对FP有反应的73%-93%的患者，50%的剂量减少仍然有效。无效者有类固醇耐药性的证据；组织学和分子标志物可以预测耐药性。ClinicalTrials.gov编号：NCT00426283
We evaluated the efficacy and safety of high-dose swallowed fluticasone propionate (FP) and dose reduction in patients with eosinophilic esophagitis (EoE) and analyzed esophageal transcriptomes to identify mechanisms. We conducted a randomized, multisite, double-blind, placebo-controlled trial of daily 1760 mcg FP in participants 3–30 years old with active EoE. Twenty-eight participants received FP and 14 received placebo. After 3 months, participants given FP who were in complete remission (CR) received 880 mcg FP daily, and participants in the FP or placebo groups who were not in CR continued or started, respectively, 1760 mcg FP daily for 3 additional months. The primary endpoint was histologic evidence for CR. Secondary endpoints were partial remission (PR), symptoms, compliance, esophageal gene expression, esophageal eosinophil count, and the relationship between clinical features and FP responsiveness. After 3 months, 65% of subjects given FP and no subjects given placebo were in CR (P=.0001); 12% of those given FP and 8% of those given placebo were in PR. In the FP group, 73% of subjects remained in CR and 20% were in PR after the daily dose was reduced by 50%. Extending FP therapy in FP-resistant participants did not induce remission. FP decreased heartburn severity (P=.041). Compliance, age, sex, atopic status, or anthropomorphic features were not associated with response to FP. Gene expression patterns in esophageal tissues of FP responders were similar to those of patients without EoE; there was evidence for heterogeneous steroid signaling in subjects that did not respond to FP. Daily administration of a high dose of FP induces histologic remission in 65%–77% of patients with EoE after 3 months. A 50% dose reduction remained effective in 73%–93% of patients that initially responded to FP. Nonresponders had evidence of steroid resistance; histologic and molecular markers may predict resistance. Clinicaltrials.gov number: NCT00426283
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