METHODS: A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (ocular surface disease index [OSDI] score and corneal staining) between baseline and week 8.
RESULTS: Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase group (but not the vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared with baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 (9.16; 33.1) ( P <0.001) at week 8 compared with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P <0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).
CONCLUSIONS: Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.
方法:前瞻性,第一阶段或第二阶段,随机化,安慰剂对照,在oGVHD患者(n=58)中,我们进行了双盲临床试验,以确定DNAase(0.1%)滴眼液每日4次、共8周的安全性和初步疗效.进行意图治疗分析以确定基线和第8周之间安全性结果测量(药物耐受性和不良事件比例)和疗效结果测量(眼表疾病指数[OSDI]评分和角膜染色)的变化。
结果:溶媒组和DNA酶组的耐受性和不良事件相似。在DNA酶组(但不是载体组)内,角膜染色显示,与基线(5.00[3.00;7.00])相比,第8周(3.50[2.75;5.00])有统计学意义和临床意义的减少.在DNA酶组中,与基线(45.5[31.8;50.0])相比,在第8周,OSDI评分还显示出18.4(9.16;33.1)的统计学上有意义的临床意义的降低(P<0.001)。与媒介物组(分别在第4周和第8周的35.7%和34.0%)相比,在DNA酶组中具有主观总体评估(SGA)和粘液排出改善的眼睛的比例(分别在第4周和第8周的55.6%和57.7%;在两个时间点P<0.0001)显著更大。
结论:使用DNAase滴眼液治疗oGVHD患者是安全的,并显示出初步疗效。脱氧核糖核酸酶I滴眼液可能会降低oGVHD患者眼表疾病的体征和症状的严重程度。