PMID- 33971353 OWN - NLM STAT- MEDLINE DCOM- 20220310 LR - 20220310 IS - 2468-6530 (Electronic) IS - 2468-6530 (Linking) VI - 6 IP - 2 DP - 2022 Feb TI - Clinical Characteristics and Outcomes of Eyes with Intraocular Inflammation after Brolucizumab: Post Hoc Analysis of HAWK and HARRIER. PG - 97-108 LID - S2468-6530(21)00162-7 [pii] LID - 10.1016/j.oret.2021.05.003 [doi] AB - PURPOSE: 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. DESIGN: Post hoc analysis of investigator-reported IOI-related AEs in HAWK and HARRIER. PARTICIPANTS: Of 1088 brolucizumab-treated eyes (3 or 6 mg), 49 eyes demonstrated at least 1 IOI-related AE and were included in this analysis. METHODS: Reports of IOI-related AEs were analyzed and descriptive statistics were provided for outcome measures. MAIN 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. RESULTS: 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. CONCLUSIONS: Findings of this analysis highlight the need for continued vigilance and monitoring for any signs of IOI-related events in patients receiving brolucizumab. CI - Copyright (c) 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. FAU - Singer, Michael AU - Singer M AD - Medical Center of Ophthalmology, University of Texas Health Science Center, San Antonio, Texas. Electronic address: msinger11@me.com. FAU - Albini, Thomas A AU - Albini TA AD - Bascom Palmer Eye Institute, University of Miami, Miami, Florida. FAU - Seres, Andras AU - Seres A AD - Budapest Retina Associates, Budapest, Hungary. FAU - Baumal, Caroline R AU - Baumal CR AD - New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts. FAU - Parikh, Soumil AU - Parikh S AD - Novartis Pharma AG, Basel, Switzerland. FAU - Gale, Richard AU - Gale R AD - York Teaching Hospital NHS Foundation Trust, University of York, York, United Kingdom. FAU - Kaiser, Peter K AU - Kaiser PK AD - Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio. FAU - Lobach, Iryna AU - Lobach I AD - Novartis Pharma AG, Basel, Switzerland. FAU - Feltgen, Nicolas AU - Feltgen N AD - Department of Ophthalmology, University Gottingen, Gottingen, Germany. FAU - Joshi, Mayur R AU - Joshi MR AD - Novartis Pharmaceuticals UK Limited, London, United Kingdom. FAU - Ziemssen, Focke AU - Ziemssen F AD - Department for Ophthalmology, Eberhard Karl University Tubingen, Tubingen, Germany. FAU - Bodaghi, Bahram AU - Bodaghi B AD - Department of Ophthalmology, Sorbonne University, APHP, Paris, France. LA - eng PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20210508 PL - United States TA - Ophthalmol Retina JT - Ophthalmology. Retina JID - 101695048 RN - 0 (Angiogenesis Inhibitors) RN - 0 (Antibodies, Monoclonal, Humanized) RN - XSZ53G39H5 (brolucizumab) SB - IM MH - Angiogenesis Inhibitors/administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized/administration & dosage/*adverse effects MH - Double-Blind Method MH - Female MH - Fluorescein Angiography/methods MH - Follow-Up Studies MH - Fundus Oculi MH - Humans MH - Inflammation/*chemically induced/diagnosis MH - Intravitreal Injections/adverse effects MH - Male MH - Middle Aged MH - Prognosis MH - Retrospective Studies MH - Time Factors MH - Tomography, Optical Coherence/methods MH - Uveitis/*chemically induced/diagnosis MH - Wet Macular Degeneration/diagnosis/drug therapy OTO - NOTNLM OT - Anti-vascular endothelial growth factor OT - Brolucizumab OT - Intraocular inflammation OT - Neovascular age-related macular degeneration EDAT- 2021/05/11 06:00 MHDA- 2022/03/11 06:00 CRDT- 2021/05/10 20:15 PHST- 2021/03/17 00:00 [received] PHST- 2021/04/14 00:00 [revised] PHST- 2021/05/03 00:00 [accepted] PHST- 2021/05/11 06:00 [pubmed] PHST- 2022/03/11 06:00 [medline] PHST- 2021/05/10 20:15 [entrez] AID - S2468-6530(21)00162-7 [pii] AID - 10.1016/j.oret.2021.05.003 [doi] PST - ppublish SO - Ophthalmol Retina. 2022 Feb;6(2):97-108. doi: 10.1016/j.oret.2021.05.003. Epub 2021 May 8.