A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.
A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease.
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DOI：
10.1016/j.ophtha.2016.02.044
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发表时间：
2016-07
期刊：
影响因子：
13.7
通讯作者：
Dana R
中科院分区：
文献类型：
--
作者：
Abud TB;Amparo F;Saboo US;Di Zazzo A;Dohlman TH;Ciolino JB;Hamrah P;Dana R
评价眼移植物抗宿主病（GVHD）患者外用他克莫司0.05%与外用甲泼尼龙0.5%的安全性和疗效。I/II期、前瞻性、随机、双盲临床试验。入选了来自40名诊断为慢性眼部GVHD的患者的80只眼。40例眼部GVHD患者随机分组; 24例患者接受0.05%他克莫司外用治疗，16例患者接受0.5%甲泼尼龙外用治疗，每日两次，持续10周，此外继续其基线治疗方案。根据不良事件的发生率评价安全性。根据受试者滴注后不适的报告评估耐受性。监测眼内压（IOP）。主要疗效终点为：角膜荧光素染色（CFS）、泪膜破裂时间（TBUT）、Schirmer试验以及眼表炎症标志物人类白细胞抗原-DR（HLA-DR）和细胞间粘附分子-1（ICAM-1）的表达。使用眼表疾病指数（OSDI）评估症状。治疗10周后，两个治疗组均未发生重大不良事件，两组的综合耐受性评分无显著差异（P=0.06）。然而，他克莫司组的烧灼感更明显（P=0.002）。在第10周时，局部使用他克莫司比甲基强的松龙更有效地降低CFS评分（分别降低55%和23%; P=0.01），并且与基线相比，TBUT显著改善（P<0.001）。他克莫司组OSDI评分降低达到统计学显著性（降低27%; P=0.02），但甲基强的松龙组的OSDI评分降低幅度较小（降低32%; P=0.06）。两组眼表上皮细胞ICAM-1表达均显著降低（他克莫司组P=0.003;甲基强的松龙组P=0.008），而HLA-DR表达仅在他克莫司组显著降低（P=0.03）。在研究期间，两组的Schirmer试验评分均未发生显著变化;第10周，甲基强的松龙组的IOP显著升高（P=0.04）。局部他克莫司0.05%是安全的，一般耐受性良好，有效治疗眼部GVHD，没有局部皮质类固醇的高血压作用。
To evaluate the safety and efficacy of topical tacrolimus 0.05% vs. topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Phase I/II, prospective, randomized, double-masked clinical trial. Eighty eyes from 40 patients diagnosed with chronic ocular GVHD were enrolled. Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients with topical methylprednisolone 0.5% twice a day for 10 weeks, in addition to continuing their baseline treatment regimen. Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subjects’ reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy endpoints were: corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer test, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the two groups (P=0.06). However, burning sensation was more pronounced with tacrolimus (P=0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P=0.01), and achieved significant improvement in TBUT when compared to baseline (P<0.001). OSDI score reduction achieved statistical significance with tacrolimus (27% reduction; P=0.02) but was marginal with methylprednisolone (32% reduction; P=0.06). ICAM-1 expression by ocular surface epithelium decreased significantly in both groups (tacrolimus P=0.003; methylprednisolone P=0.008), while HLA-DR expression significantly decreased only in the tacrolimus group (P=0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P=0.04). Topical tacrolimus 0.05% is safe, generally well tolerated and effective for the treatment of ocular GVHD, without the hypertensive effects of topical corticosteroids.