Importance An investigation of the treatment effect of lifitegrast ophthalmic solution, 5.0%, in different subgroups by severity of dry eye disease (DED) seems warranted.

Objective To explore the heterogeneity across different subgroups of DED and identify which participants were most likely to achieve clinically meaningful benefit with lifitegrast treatment.

Design, Setting, and Participants This post hoc responder analysis was performed using the data from the phase 3 OPUS-2 and OPUS-3 studies, which were 12-week, prospective, double-masked, multicenter, placebo-controlled, randomized, parallel-arm clinical trials that previously demonstrated the efficacy of lifitegrast in DED. Pooled data were stratified into 4 subgroups based on severity of inferior corneal staining score (ICSS; ≤1.5 vs >1.5) and eye dryness score (EDS; <60 or ≥60) at baseline. Data were collected from December 7, 2012, to October 5, 2015, and post hoc analysis was performed from April 14, 2020, to July 30, 2021.

Interventions Lifitegrast or placebo twice daily for 84 days.

Main Outcomes and Measures Proportion of participants with (1) a clinically meaningful improvement in signs (ICSS or total corneal staining score [TCSS]) and symptoms (EDS or global visual analog scale [VAS]) and (2) a composite response for a given sign and symptom end point pair at day 84 were measured. Clinically meaningful improvement was defined as at least 30% improvement in symptoms (EDS or global VAS) and either at least a 1-point improvement in ICSS or at least a 3-point improvement in TCSS. For the composite responder analysis, the end point pairs were defined as at least a 30% reduction in EDS and at least a 1-point improvement in ICSS; at least a 30% reduction in EDS and at least a 3-point improvement in TCSS; at least a 30% improvement in global VAS and at least a 1-point improvement in ICSS; and at least a 30% improvement in global VAS and at least a 3-point improvement in TCSS.

Results In total, 1429 participants (716 in the placebo group and 713 in the lifitegrast group) were analyzed (1087 women [76.1%]; mean [SD] age, 58.7 [14.3] years). For the overall pooled population, responder and composite responder rates favored lifitegrast vs placebo (odds ratio range, 1.29 [95% CI, 1.05-1.59] to 2.10 [95% CI, 1.68-2.61]; P ≤ .02). In the composite analysis, the subgroup with ICSS of greater than 1.5 and EDS of at least 60 at baseline (ie, moderate to severe DED) demonstrated a 1.70- to 2.11-fold higher odds of achieving clinically meaningful improvement with lifitegrast across all sign and symptom end point pairs (P ≤ .001).

Conclusions and Relevance These post hoc findings suggest that lifitegrast ophthalmic solution, 5.0%, treatment may be associated with a response in participants with moderate to severe signs and symptoms of DED.

Trial Registration ClinicalTrials.gov Identifier: NCT02284516

重要性 似乎有必要根据干眼病 (DED) 的严重程度对不同亚组中 5.0% Lifitegrast 滴眼液的治疗效果进行调查。

目的 探讨 DED 不同亚组之间的异质性，并确定哪些参与者最有可能通过 lifitegrast 治疗获得具有临床意义的益处。

设计、设置和参与者 这项事后响应者分析是使用来自 3 期 OPUS-2 和 OPUS-3 研究的数据进行的，这些研究是 12 周、前瞻性、双盲、多中心、安慰剂对照、随机、平行-arm 临床试验，之前证明了 lifitegrast 在 DED 中的功效。根据基线时劣质角膜染色评分（ICSS；≤1.5 vs >1.5）和眼干评分（EDS；<60 或≥60）的严重程度将汇总数据分为 4 个亚组。数据收集时间为 2012 年 12 月 7 日至 2015 年 10 月 5 日，事后分析时间为 2020 年 4 月 14 日至 2021 年 7 月 30 日。

干预 Lifitegrast 或安慰剂每天两次，持续 84 天。

主要成果和措施 (1) 体征（ICSS 或总角膜染色评分 [TCSS]）和症状（EDS 或全局视觉模拟评分 [VAS]）和 (2) 对给定体征和症状的复合反应的参与者比例测量第 84 天的终点对。具有临床意义的改善被定义为症状（EDS 或整体 VAS）至少改善 30%，并且 ICSS 至少改善 1 点或 TCSS 至少改善 3 点。对于复合反应者分析，终点对定义为 EDS 至少减少 30% 和 ICSS 至少改善 1 点；EDS 至少降低 30%，TCSS 至少提高 3 个点；全球 VAS 至少提高 30%，ICSS 至少提高 1 个百分点；

结果 总共分析了 1429 名参与者（安慰剂组 716 名，利泰格司特组 713 名）（1087 名女性 [76.1%]；平均 [SD] 年龄，58.7 [14.3] 岁）。对于总体汇总人群，响应者和复合响应者的比率更倾向于利替格司特与安慰剂（优势比范围，1.29 [95% CI，1.05-1.59] 至 2.10 [95% CI，1.68-2.61]；P  ≤ .02）。在综合分析中，基线时 ICSS 大于 1.5 且 EDS 至少为 60 的亚组（即中度至重度 DED）显示，在所有体征和症状终点对 ( P  ≤ .001)。

结论和相关性 这些事后研究结果表明，5.0% 的利福司特滴眼液治疗可能与具有中度至重度 DED 体征和症状的参与者的反应有关。

试验注册 ClinicalTrials.gov 标识符：NCT02284516