口服黏性类固醇治疗嗜酸细胞性食管炎优于喷雾剂

北卡罗来纳大学教堂山分校的Evan S.Dellon博士及其同事在《胃肠病学》8月刊报告称，一种可吞服的黏性局部类固醇药物在减少嗜酸细胞性食管炎(EoE)患者嗜酸细胞计数的效果方面优于喷雾溶液，但嗜酸细胞减少与吞咽困难改善并不相关。(Gastroenterology 2012 May 7 [doi:10.1053/j.gastro.2012.04.049])。

这项首次比较局部类固醇激素两种给药方法治疗EoE以及首次考察口服黏性布地奈德用于成人EoE治疗的研究，入组22例吞咽困难患者，随机给予1 mg布地奈德治疗，2次/d，治疗8周，其中11例采用喷雾后吞服给药方式(NEB)，另外11例口服黏性混悬溶液(OVB)。患者平均年龄35岁，60%为男性。

基线时，NEB组最大嗜酸细胞计数为101个/高倍视野，而OVB组为83个/高倍视野(P=0.62)；治疗后，NEB组最大计数为89个/高倍视野，而OVB组为11个/高倍视野(P=0.02)。研究者应用核素显像方法评价黏膜药物接触时间，中位食管排空曲线下面积(AUC)较高即表示接触时间较长。结果发现，OVB组AUC的确高于NEB组，但黏膜药物接触时间与嗜酸细胞计数下降相关，与药物制剂类型无关(P=0.001)。

“梅奥吞咽困难问卷-30d”(尚未经EoE患者验证)对吞咽困难改善情况的评价结果显示，与嗜酸细胞计数不同，两组吞咽困难症状评分均有所改善，即使排除基线接受试管扩张治疗的患者后，吞咽困难改善仍然存在。吞咽困难改善与内镜或组织学检查结果改善均无关联。

在副作用方面，有3例患者治疗后内镜检查为无症状性念珠菌性食管炎，NEB组1例患者因鼻出血放弃治疗，但未见其他副作用或不良事件。此外，肾上腺皮质素刺激试验未见患者肾上腺皮质功能不全，8周后患者血清中未检出布地奈德，表明仅发挥局部作用而非全身作用。

研究者承认该研究存在样本量较小以及未设安慰剂对照组等局限性。但他们认为，该研究的主要结果具有足够效能，且证明估算检验效能的效应量是准确的。此外，核素显像机制分析进一步证实了主要结果，并为该领域引入一种新的定量方法，对未来药物开发具有指导意义。虽然吞咽剂型比吸入剂使用更方便，但前者还未上市，目前凝胶、散剂和口溶片等尚处于开发阶段。

研究者报告其个人无相关利益冲突，但该研究得到布地奈德制造商阿斯利康公司的部分资助。

爱思唯尔  版权所有

By: DENISE NAPOLI, Internal Medicine News Digital Network

A swallowed, viscous solution of topical steroids was more effective at reducing eosinophil counts than was a nebulized solution in eosinophilic esophagitis, Dr. Evan S. Dellon and his colleagues reported in the August issue of Gastroenterology.

However, in what the authors called "the first study comparing two methods of topical steroid delivery for treatment of EoE, and the first examining the use of oral viscous budesonide in adults," they also found that decreased eosinophils did not correlate with improvements in dysphagia.

Dr. Dellon and his colleagues at the University of North Carolina at Chapel Hill randomized 22 dysphagia patients to budesonide 1 mg twice daily for 8 weeks, either nebulized and then swallowed (n = 11) or in an oral viscous slurry formulation (n = 11). The patients’ mean age was 35 years; 60% were men.

At baseline, the maximum eosinophil count for the nebulizer treatment group was 101 eosinophils per high-power field; for the viscous slurry group, it was 83 (P = .62).

Following treatment, the nebulizer group had a maximum count of 89 eosinophils per high-power field, compared with a maximum of 11 in the viscous slurry group (P = .02).

The authors then used nuclear scintigraphy to assess mucosal medication contact time, where higher median areas under the esophageal emptying curve (AUC) were assumed to mean greater contact time.

They found that the oral viscous preparation AUC was indeed higher for the viscous preparation than for the nebulized budesonide; however, "higher mucosal contact time correlated with the decrease in eosinophil count regardless of treatment type (P = .001)," they wrote.

The researchers also assessed dysphagia improvement, as measured on the Mayo Dysphagia Questionnaire-30 Day (which has not been validated in eosinophilic esophagitis).

 "In contrast to the eosinophil counts, dysphagia symptom scores improved in both groups, and this improvement persisted after excluding patients who received esophageal dilation at baseline" they reported.

Nor did improvement in dysphagia correlate with endoscopic or histologic improvement.

Looking at side effects, Dr. Dellon and his colleagues reported that three patients had asymptomatic candidal esophagitis on posttreatment endoscopy, and that one patient in the nebulizer group withdrew because of epistaxis, but that no other side effects or adverse events occurred.

They added that no patients had adrenal insufficiency by cortisol stimulation testing, and no budesonide was detected in patients’ serum after 8 weeks, which suggested a "topical, rather than systemic activity."

The researchers did concede several limitations to this study, including its small sample size and the lack of a placebo control.

However, the study "was adequately powered for the primary outcomes, and the effect size estimates for the power calculations proved to be accurate," they noted.

"The mechanistic assessment with nuclear scintigraphy corroborated the main results and introduced new quantitative methodology to this area, which may guide future drug development," the researchers added.

While "it makes intuitive sense" that a swallowed formulation would be easier to administer than an inhaler, "the ideal medication delivery system does not yet exist," although several are currently under development, including gels, powders, and dissolving tablets, the authors noted.

They disclosed that they had no personal conflicts of interest, but the study was supported in part by AstraZeneca, maker of budesonide.