A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease
A randomized, placebo-controlled trial of oral beclomethasone dipropionate as a prednisone-sparing therapy for gastrointestinal graft-versus-host disease
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DOI：
10.1182/blood-2006-05-021139
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发表时间：
2007-05-15
期刊：
影响因子：
20.3
通讯作者：
McDonald, George B.
中科院分区：
文献类型：
--
作者：
Hockenbery, David M.;Cruickshank, Scott;McDonald, George B.
我们检验了口服丙酸倍氯米松（BDP）可以控制厌食、呕吐和腹泻患者胃肠道移植物抗宿主病（GVHD）的假设。患者随机接受泼尼松治疗10天，口服BDP 8 mg/d（n = 62）或安慰剂（n = 67）片剂治疗50天。在研究第10天，泼尼松迅速减量，同时继续使用研究药物。在意向治疗基础上，BDP组在研究第50天（风险比[HR] 0.63，95%置信区间[CI] 0.35-1.13）和30天随访时（HR 0.55，95% CI 0.32-0.93）GVHD治疗失败的风险降低。在研究第10天有资格接受泼尼松减量的患者中，GVHD治疗失败的风险在研究第50天和第80天均显著降低（HR分别为0.39和0.38）。移植后第200天，5名随机分配至BDP组的患者死亡，而安慰剂组有16名患者死亡，死亡风险降低67%（HR 0.33，P = 0.03）。在47例非亲缘和HLA错配干细胞移植受者中，与安慰剂组相比，BDP组移植第200天的死亡率降低了91%（HR 0.09，P = .02）。生存益处可持续至随机化后1年。口服BDP可预防泼尼松减量后胃肠道GVHD复发;接受BDP治疗的患者生存率在统计学上显著更高。
We tested the hypothesis that oral beclomethasone dipropionate (BDP) would control gastrointestinal graft-versus-host disease (GVHD) in patients with anorexia, vomiting, and diarrhea. Patients were randomized to prednisone for 10 days and either oral BDP 8 mg/d (n = 62) or placebo (n = 67) tablets for 50 days. At study day 10, prednisone was rapidly tapered while continuing study drug. On an intent-to-treat basis, the risk of GVHD-treatment failure was reduced for the BDP group at study day 50 (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.35-1.13) and at 30 days follow-up (HR 0.55, 95% CI 0.32-0.93). Among patients eligible for prednisone taper at study day 10, the risk of GVHD-treatment failure was significantly reduced at both study days 50 and 80 (HR 0.39 and 0.38, respectively). By day 200 after transplantation, 5 patients randomized to BDP had died compared with 16 deaths on placebo, a 67% reduction in the hazard of mortality (HR 0.33, P = .03). In 47 recipients of unrelated and HLA-mis-matched stem cells, mortality at transplantation day 200 was reduced by 91% in the BDP group compared with placebo (HR 0.09, P = .02). The survival benefit was durable to 1 year after randomization. Oral BDP prevents relapses of gastrointestinal GVHD following tapering of prednisone; survival is statistically significantly better among patients receiving BDP.