Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER
An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related...
Uložené v:
| Vydané v: | Ophthalmology (Rochester, Minn.) Ročník 128; číslo 7; s. 1050 |
|---|---|
| Hlavní autori: | , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
01.07.2021
|
| Predmet: | |
| ISSN: | 1549-4713, 1549-4713 |
| On-line prístup: | Zistit podrobnosti o prístupe |
| Tagy: |
Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
|
| Abstract | An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).
A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).
Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).
The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.
Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.
Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.
This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD. |
|---|---|
| AbstractList | An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).PURPOSEAn independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD).A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).DESIGNA post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328).Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).PARTICIPANTSPatients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes).The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.METHODSThe SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group.Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.MAIN OUTCOME MEASURESWithin this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset.Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.RESULTSFifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%.This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD.CONCLUSIONSThis analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD. An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI), endophthalmitis, and retinal arterial occlusion in the phase 3 HAWK and HARRIER trials of brolucizumab versus aflibercept in neovascular age-related macular degeneration (nAMD). A post hoc analysis of a subset of data from two 2-year, double-masked, multicenter, active-controlled randomized phase 3 trials (NCT02307682, NCT02434328). Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye were randomized and treated in HAWK/HARRIER. The SRC reviewed data from cases of investigator-reported IOI (60/1088 brolucizumab-treated eyes; 8/729 aflibercept-treated eyes). The SRC received details and images (color fundus photography, fluorescein angiography, and OCT) for all investigator-determined cases of IOI, retinal arterial occlusion, and endophthalmitis. Cases were reviewed in detail by ≥2 readers, then adjudicated by the SRC as a group. Within this patient subset: incidence of IOI, signs and incidence of retinal vasculitis and/or retinal vascular occlusion, and visual acuity loss; time since first brolucizumab injection to IOI event onset; and frequency of visual acuity loss after brolucizumab injection by time of first IOI event onset. Fifty brolucizumab-treated eyes were considered to have definite/probable drug-related events within the spectrum of IOI, retinal vasculitis, and/or vascular occlusion. On the basis of these cases, incidence of definite/probable IOI was 4.6% (IOI + vasculitis, 3.3%; IOI + vasculitis + occlusion, 2.1%). There were 8 cases (incidence 0.74%) of at least moderate visual acuity loss (≥15 ETDRS letters) in eyes with IOI (7 in eyes with IOI + vasculitis + occlusion). Of the 8 cases, 5 experienced their first IOI-related event within 3 months of the first brolucizumab injection (increasing to 7/8 within 6 months). Incidence of IOI in aflibercept-treated eyes was 1.1%, with at least moderate visual acuity loss in 0.14%. This analysis of IOI cases after brolucizumab injection identified signs of retinal vasculitis with or without retinal vascular occlusion and an associated risk of visual acuity loss. The findings will help physicians to evaluate the risks and benefits of brolucizumab treatment for nAMD. |
| Author | Srivastava, Sunil K Monés, Jordi Kaiser, Peter K Heier, Jeffrey S Albini, Thomas A Korobelnik, Jean-Francois Murray, Timothy G Jaffe, Glenn J Holz, Frank G Tadayoni, Ramin Kim, Ivana K Pruente, Christian |
| Author_xml | – sequence: 1 givenname: Jordi surname: Monés fullname: Monés, Jordi organization: Institut de la Màcula, Barcelona, Spain, Barcelona Macula Foundation, Barcelona, Spain – sequence: 2 givenname: Sunil K surname: Srivastava fullname: Srivastava, Sunil K organization: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio – sequence: 3 givenname: Glenn J surname: Jaffe fullname: Jaffe, Glenn J organization: Department of Ophthalmology, Duke University, Durham, North Carolina – sequence: 4 givenname: Ramin surname: Tadayoni fullname: Tadayoni, Ramin organization: Departement Hospitalo-Universitaire Vision et Handicaps, Paris, France; Université de Paris, Ophthalmology Department, AP-HP, Hôpital Lariboisière, Rothschild Foundation Hospital, Paris, France – sequence: 5 givenname: Thomas A surname: Albini fullname: Albini, Thomas A organization: Bascom Palmer Eye Institute, The University of Miami, Miami, Florida – sequence: 6 givenname: Peter K surname: Kaiser fullname: Kaiser, Peter K organization: Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio – sequence: 7 givenname: Frank G surname: Holz fullname: Holz, Frank G organization: Department of Ophthalmology, University of Bonn, Bonn, Germany – sequence: 8 givenname: Jean-Francois surname: Korobelnik fullname: Korobelnik, Jean-Francois organization: CHU Bordeaux, Service d'ophtalmologie, Bordeaux, France; University Bordeaux, INSERM, BPH, Bordeaux, France – sequence: 9 givenname: Ivana K surname: Kim fullname: Kim, Ivana K organization: Dr. Kim participated in this study as a consultant to Novartis independent of her faculty appointment in the Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts – sequence: 10 givenname: Christian surname: Pruente fullname: Pruente, Christian organization: Department of Ophthalmology, University of Basel, Basel, Switzerland; Department of Ophthalmology, Kantonsspital Baselland, Liestal, Switzerland; Institute of Molecular and Clinical Ophthalmology Basel (IOB), Basel, Switzerland – sequence: 11 givenname: Timothy G surname: Murray fullname: Murray, Timothy G organization: Murray Ocular Oncology and Retina, Miami, Florida – sequence: 12 givenname: Jeffrey S surname: Heier fullname: Heier, Jeffrey S email: jsheier@eyeboston.com organization: Ophthalmic Consultants of Boston, Boston, Massachusetts. Electronic address: jsheier@eyeboston.com |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/33207259$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkEtPwzAQhC0Eog_4Bwj5yKEJtuMmDbdSFVJRqSjicYwcZ6O6OHGpnVZw538ToCAuu6vRNzPS9tBhbWpA6IwSnxIaXq58s166pfAZYa1EfULpAerSIY89HtHg8N_dQT1rV4SQMAz4MeoEASMRG8Zd9JEq-4JNiWd1qUVVCadMPcApOFULjZ-ElY1WTtkBFnXxpy-k1I1tUS8FLRwUeLqF2lm8U26JrzdGN1K9N5XIr_C9sQ4nRrbmrYLdV1kyfr77zkvGaTqbpifoqBTawul-99HjzfRhknjzxe1sMp57S8aHzpMCOBEs5tCOmJcsJ4EIeUG5CEY8Llg44jkpQ1YEwGXOymEMcRQRCUVUQslZH1385K435rUB67JKWQlaixpMYzPGQ8ZJHFDSoud7tMkrKLL1RlVi85b9vo59Au3UdDY |
| ContentType | Journal Article |
| Copyright | Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
| Copyright_xml | – notice: Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
| DBID | NPM 7X8 |
| DOI | 10.1016/j.ophtha.2020.11.011 |
| DatabaseName | PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1549-4713 |
| ExternalDocumentID | 33207259 |
| Genre | Journal Article |
| GroupedDBID | --- --K .1- .FO 0R~ 123 1B1 1P~ 1~5 4.4 457 4G. 53G 5RE 7-5 71M AAEDT AAEDW AALRI AAXUO ABCQX ABFRF ABJNI ABLJU ABMAC ABOCM ACGFO ACGFS ACIUM ACNCT AEFWE AENEX AEVXI AFRHN AFTJW AITUG AJUYK AKRWK ALMA_UNASSIGNED_HOLDINGS AMRAJ BELOY C5W CS3 DU5 EBS EFJIC F5P FDB GBLVA IHE J1W K-O KOM L7B M27 M41 MO0 N9A NPM O9- OF- OPF OQ~ P2P ROL RPZ SDG SEL SES SSZ UNMZH UV1 WH7 XH2 Z5R 7X8 EFKBS |
| ID | FETCH-LOGICAL-h245t-cae40a294ea2994f2b03a64d14a3849d2684b0f62d3e4cb2f59e9770ced7fef42 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 265 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000667677700018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1549-4713 |
| IngestDate | Sun Sep 28 07:46:32 EDT 2025 Thu Jan 02 22:58:39 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 7 |
| Keywords | neovascular age-related macular degeneration intraocular inflammation safety brolucizumab retinal vasculitis retinal arterial occlusion retinal occlusive vasculitis retinal vascular occlusion |
| Language | English |
| License | Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-h245t-cae40a294ea2994f2b03a64d14a3849d2684b0f62d3e4cb2f59e9770ced7fef42 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 |
| OpenAccessLink | https://hal.science/hal-03163954 |
| PMID | 33207259 |
| PQID | 2462409310 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2462409310 pubmed_primary_33207259 |
| PublicationCentury | 2000 |
| PublicationDate | 2021-07-01 |
| PublicationDateYYYYMMDD | 2021-07-01 |
| PublicationDate_xml | – month: 07 year: 2021 text: 2021-07-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Ophthalmology (Rochester, Minn.) |
| PublicationTitleAlternate | Ophthalmology |
| PublicationYear | 2021 |
| SSID | ssj0006634 |
| Score | 2.7025905 |
| Snippet | An independent Safety Review Committee (SRC), supported by Novartis Pharma AG, analyzed investigator-reported cases of intraocular inflammation (IOI),... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| StartPage | 1050 |
| Title | Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/33207259 https://www.proquest.com/docview/2462409310 |
| Volume | 128 |
| WOSCitedRecordID | wos000667677700018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LTxsxELbKQ4gLlJZXoZWResTFsZ3ddS8oQkFBiIBWFHKLvH4oEbAbCOHAnf_dGe-mnCpV6sWHlexdjWfn-c0MId9t5pPEcMeU5oap4DKWhUKzAMwjhfW8FVQcNpH2-9lgoK-agNu0gVXOZWIU1K6yGCM_EioB5aPBGjmePDKcGoXZ1WaExgJZkmDKIFeng_du4aBNY1YZfCAGQljOS-civquajJ5H2HlIoNz4wVutvxuZUdmcrv_vZ34ka42ZSTs1X2yQD778RFYumkT6Z_KWj6d3tAr0rAzAE3X94iHNsQAa9t1EfCq2OzqkpnR_nl9aez_D-BqLIDrvaBfxklOK4VwKLv39zI5fZw-m-ElxDDDtVZbW6Qd8Wa9zex7P63Xy_Kybb5Jfp93rkx5rJjKwkVDtZ2aNV9wIrTwsWgVRcGkS5VrKyExph61jCh4S4aRXthChrT0YmNx6lwYflNgii2VV-h1CHUiPxEWHC70enYU22ELK8KC9K2S6Sw7mBB4Cx2Maw5S-mk2H7yTeJdv1LQ0ndWuOoZSCp3Dal3_YvUdWBQJUIvZ2nywF-N_9V7JsX4C6T98iK8Hav7r4DeyM0rM |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Risk+of+Inflammation%2C+Retinal+Vasculitis%2C+and+Retinal+Occlusion-Related+Events+with+Brolucizumab%3A+Post+Hoc+Review+of+HAWK+and+HARRIER&rft.jtitle=Ophthalmology+%28Rochester%2C+Minn.%29&rft.au=Mon%C3%A9s%2C+Jordi&rft.au=Srivastava%2C+Sunil+K&rft.au=Jaffe%2C+Glenn+J&rft.au=Tadayoni%2C+Ramin&rft.date=2021-07-01&rft.eissn=1549-4713&rft_id=info:doi/10.1016%2Fj.ophtha.2020.11.011&rft_id=info%3Apmid%2F33207259&rft_id=info%3Apmid%2F33207259&rft.externalDocID=33207259 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1549-4713&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1549-4713&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1549-4713&client=summon |