Long-Term Budesonide Maintenance Treatment Is Partially Effective for Patients With Eosinophilic Esophagitis
Long-Term Budesonide Maintenance Treatment Is Partially Effective for Patients With Eosinophilic Esophagitis
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DOI：
10.1016/j.cgh.2011.01.017
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发表时间：
2011-05-01
影响因子：
12.6
通讯作者：
Simon, Hans-Uwe
中科院分区：
文献类型：
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作者：
Straumann, Alex;Conus, Sebastien;Simon, Hans-Uwe
研究目的：局部应用皮质类固醇可有效诱导嗜酸性粒细胞性食管炎（EoE）患者的临床和组织学缓解。然而，这种慢性炎症性疾病的最佳长期管理策略尚未确定。方法：在一项为期50周的随机、双盲、安慰剂对照试验中，我们评估了28例患者每日两次吞服布地奈德（每次0.25 mg）维持静止期EoE缓解的疗效。通过临床、内镜、组织学、免疫组织学和内镜超声检查评估治疗前和治疗后活动。主要终点是治疗在组织学缓解中维持EoE的能力。次要终点为症状控制、组织重塑预防和安全性。研究结果：在给予低剂量布地奈德的患者中，食管嗜酸性粒细胞的负荷从0.4增加到31.8嗜酸性粒细胞/高倍视野（P = 0.017）。在接受安慰剂治疗的患者中，嗜酸性粒细胞/高倍视野的负荷从0.7增加到65.0（P = 0.0001）;这种增加明显大于接受布地奈德治疗的患者（P = 0.024）。两组的症状评分以相似的方式发展。布地奈德，而不是安慰剂，减少炎症，上皮细胞凋亡和重塑事件的非嗜酸性粒细胞标志物。与对照组相比，患者的食管壁明显增厚（3.05 mm vs 2.18 mm; P <0.0001）。布地奈德治疗与粘膜厚度显著降低（0.75-0.45 mm; P = 0.025）相关，但上皮厚度保持稳定（261.22 vs 277.23 μ m; P = 0.576）。未发生严重不良事件。结论：低剂量布地奈德在维持组织学和临床缓解的EoE方面比安慰剂更有效。食管重塑的迹象显示出正常化的趋势。局部皮质类固醇的长期给药耐受性良好，未诱导上皮萎缩。
BACKROUND & AIMS: Topical corticosteroids are effective in inducing clinical and histologic remission in patients with eosinophilic esophagitis (EoE). However, the best longterm management strategy for this chronic inflammatory disease has not been determined. METHODS: In a randomized, double-blind, placebo-controlled, 50-week trial, we evaluated in 28 patients the efficacy of twice-daily swallowed budesonide (0.25 mg each) to maintain quiescent EoE in remission. Pretreatment and posttreatment activity was assessed clinically, endoscopically, histologically, immunohistologically, and by endosonography. The primary end point was the therapy's ability to maintain EoE in histologic remission. Secondary end points were efficacy in symptom control, prevention of tissue remodeling, and safety. RESULTS: In patients given low-dose budesonide, the load of esophageal eosinophils increased from 0.4 to 31.8 eosinophils/ high-power field (P = .017). In patients given placebo, the load increased from 0.7 to 65.0 eosinophils/ high-power field (P = .0001); this increase was significantly greater than in patients given budesonide (P = .024). The symptom scores developed in a similar manner in the 2 groups. Budesonide, but not placebo, reduced noneosinophilic markers of inflammation, epithelial cell apoptosis, and remodeling events. Compared with control individuals, patients had significantly thickened esophageal walls, based on endosonography (3.05 vs 2.18 mm; P < .0001). Budesonide therapy was associated with a significant reduction in mucosal thickness (0.75-0.45 mm; P = .025), but epithelial thickness remained stable (261.22 vs 277.23 mu m; P = .576). No serious adverse events occurred. CONCLUSIONS: Low-dose budesonide is more effective than placebo in maintaining EoE in histologic and clinical remission. Signs of esophageal remodeling showed a trend toward normalization. Long-term administration of topical corticosteroids was well tolerated without induction of epithelial atrophy.