Medical Center of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas.
Bascom Palmer Eye Institute, University of Miami, Miami, Florida.
Ophthalmol Retina. 2022 Feb;6(2):97-108. doi: 10.1016/j.oret.2021.05.003. Epub 2021 May 8.
This analysis of the pivotal phase 3 HAWK and HARRIER trials aimed to provide insights on the timing of presentation, management, and outcomes of intraocular inflammation (IOI)-related adverse events (AEs), as reported by investigators in these trials.
Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER.
Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis.
Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures.
Incidence and description of eyes with IOI-related AEs, timing of presentation, management, clinical outcomes, and brolucizumab treatment after the first IOI-related AE.
Seventy IOI-related AEs were reported in 49 eyes. Before the onset of first IOI-related AE, eyes received a mean ± standard deviation (SD) of 3.9 ± 2.2 brolucizumab injections. Median time to first IOI-related AE from the last administered brolucizumab injection was 18.0 days (interquartile range, 4.0-29.0 days). Of the 70 AEs, 61 (87.1%) were treated, most with topical corticosteroids; systemic and intraocular corticosteroids were used for 3 AEs each. Overall, inflammation resolved completely in 39 eyes (79.6%), resolved with sequelae in 5 eyes (10.2%), and did not resolve in 5 eyes (10.2%) by end-of-study (EOS). Overall, the mean ± SD best-corrected visual acuity (BCVA) change from baseline to EOS, before AE to the lowest BCVA in 3 months after AE, and from before AE to EOS were -0.84 ± 20.6 , -16.31 ± 17.6, and -0.22 ± 18.9 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, respectively. Of the 36 eyes (73.5%) that continued with brolucizumab therapy after the first IOI-related AE, 24 completed the trials and 12 discontinued; mean ± SD BCVA change in these eyes was 2.6 ± 17.6, 7.8 ± 13.2, and -7.7 ± 21.3 ETDRS letters, respectively, from baseline to EOS. The remaining 13 eyes (26.5%) were not treated with brolucizumab after first IOI-related AE and showed a mean ± SD BCVA change of -10.4 ± 25.5 ETDRS letters from baseline to EOS.
Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab.
本分析旨在对关键的 3 期 HAWK 和 HARRIER 试验进行分析，以深入了解研究者报告的与眼内炎症（IOI）相关的不良事件（AE）的发生时间、管理和结局。
HAWK 和 HARRIER 试验中研究者报告的与 IOI 相关 AE 的事后分析。
在 1088 只接受 brolucizumab 治疗的眼中（3 或 6mg），有 49 只眼出现了至少 1 次与 IOI 相关的 AE，并纳入本分析。
分析与 IOI 相关的 AE 报告，并提供结局测量的描述性统计数据。
出现与 IOI 相关的 AE 的眼的发生率和描述、发病时间、管理、临床结局以及首次与 IOI 相关的 AE 后 brolucizumab 的治疗情况。
在 49 只眼中报告了 70 次与 IOI 相关的 AE。在首次发生与 IOI 相关的 AE 之前，这些眼接受了平均 ± 标准差（SD）3.9 ± 2.2 次 brolucizumab 注射。从最后一次接受 brolucizumab 注射到首次发生与 IOI 相关的 AE 的中位时间为 18.0 天（四分位距，4.0-29.0 天）。在 70 次 AE 中，61 次（87.1%）接受了治疗，其中大部分使用了局部皮质类固醇；3 次使用了全身皮质类固醇，3 次使用了眼内皮质类固醇。总体而言，39 只眼（79.6%）的炎症完全消退，5 只眼（10.2%）出现后遗症消退，5 只眼（10.2%）未消退。在研究结束时（EOS），总体最佳矫正视力（BCVA）从基线到 EOS 的平均 ± SD 变化为-0.84 ± 20.6，AE 前到 AE 后 3 个月最低 BCVA 的平均 ± SD 变化为-16.31 ± 17.6，AE 前到 EOS 的平均 ± SD 变化为-0.22 ± 18.9。在首次发生与 IOI 相关的 AE 后继续接受 brolucizumab 治疗的 36 只眼中（73.5%），有 24 只完成了试验，12 只停药；这些眼的平均 ± SD BCVA 从基线到 EOS 的变化分别为 2.6 ± 17.6、7.8 ± 13.2 和-7.7 ± 21.3 ETDRS 字母。其余 13 只眼（26.5%）在首次发生与 IOI 相关的 AE 后未接受 brolucizumab 治疗，从基线到 EOS 的平均 ± SD BCVA 变化为-10.4 ± 25.5 ETDRS 字母。
本分析结果强调了在接受 brolucizumab 治疗的患者中，需要持续警惕并监测任何与 IOI 相关事件的迹象。
