ABSTRACT

Purpose

Impaired tear production – a common sign of keratoconjunctivitis sicca (KCS) – is associated with qualitative or quantitative tear deficiency. OTX-101 0.09% is a novel, nanomicellar formulation of cyclosporine A approved in the US for increasing tear production in patients with KCS. We present a pooled analysis of the phase 2b/3 and phase 3 studies evaluating the effect of OTX-101 on tear production in a subgroup of patients with keratoconjunctivitis sicca with severely impaired tear production (Schirmer’s score <5 mm in either eye at baseline).

Methods

In these randomized, double-masked studies, patients instilled 1 drop OTX-101 or vehicle per eye twice daily for 84 days. Pooled efficacy endpoints included percent (%) of patients with ≥10 mm change from baseline and mean change from baseline in Schirmer’s score at day 84. Pooled safety endpoints included adverse event monitoring.

Results

Subgroup analyses included 133 and 113 patients receiving OTX-101 and vehicle, respectively. Mean baseline (BL) Schirmer’s score ± standard deviation was 2.7 ± 1.2 for OTX-101 and 2.5 ± 1.1 mm for vehicle (P = .3203). On day 84, number (%) of patients with ≥10 mm Schirmer’s score change from baseline was 30 (22.6%) and 12 (10.6%, P = .0168); mean change from baseline ± standard deviation was 5.5 ± 8.0 and 3.6 (6.0, P = .0405) mm for OTX-101 and vehicle, respectively. Adverse events were mostly mild and did not require treatment.

Conclusion

OTX-101 administered twice daily for 84 days significantly improved tear production vs vehicle in patients with severely impaired tear production, as evidenced by significantly larger proportion of patients with ≥10 mm increases from baseline and higher mean change from baseline in Schirmer’s scores

中文翻译：

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OTX-101对严重泪液缺乏性干眼病患者泪液产生的影响：2b/3 期和 3 期研究的汇总分析

摘要

目的

泪液产生受损——干燥性角结膜炎 (KCS) 的常见征兆——与定性或定量的泪液不足有关。OTX-101 0.09% 是一种新型的环孢霉素 A 纳米胶束制剂，在美国获批用于增加 KCS 患者的泪液产生。我们对 2b/3 期和 3 期研究进行汇总分析，评估 OTX-101 对泪液产生严重受损的干燥性角结膜炎患者亚组泪液产生的影响（基线时每只眼睛的 Schirmer 评分 <5 mm） .

方法

在这些随机、双盲研究中，患者每只眼睛每天两次滴注 1 滴 OTX-101 或载体，持续 84 天。汇总疗效终点包括第 84 天 Schirmer 评分与基线变化≥10 mm 和平均变化的患者百分比 (%)。汇总安全终点包括不良事件监测。

结果

亚组分析包括分别接受 OTX-101 和载体的 133 和 113 名患者。OTX-101 的平均基线 (BL) Schirmer 评分 ± 标准偏差为 2.7 ± 1.2，车辆为 2.5 ± 1.1 mm ( P = .3203)。在第 84 天，与基线相比 Schirmer 评分变化≥10 mm 的患者数量 (%) 为 30 (22.6%) 和 12 (10.6%, P = .0168)；OTX-101 和车辆的平均变化从基线 ± 标准偏差分别为 5.5 ± 8.0 和 3.6 (6.0, P = .0405) mm。不良事件大多是轻微的，不需要治疗。

结论

与载体相比，OTX-101 每天给药两次，持续 84 天显着改善泪液产生严重受损的患者的泪液产生，这可以从基线增加 ≥ 10 mm 的患者比例显着增加以及 Schirmer 评分从基线的平均变化更高来证明