Real-world Evaluation of Brolucizumab for the Treatment of Neovascular (Wet) Age-related Macular Degeneration (AMD) (IRIS Study)

This study was a retrospective cohort study of patients to assess the early insights into real-world safety among wet AMD patients initiating brolucizumab. Evidence was generated to describe their patient characteristics and clinical outcomes. The study was conducted using the IRIS Registry.

Study Overview

• Status: Completed
• Conditions: Age-related Macular Degeneration (AMD)
• Intervention / Treatment: Drug: Brolucizumab

Detailed Description

IRIS Registry EHR data from patients with wet AMD who initiated brolucizumab were analyzed in this study.

Identification period of the index date (index period): The patients fulfilling the selection criteria was identified

• Index date: Defined as the date of the earliest brolucizumab injection
• Study Period: The period from the first patient eye exposure to brolucizumab to the last follow-up recorded
• Pre-index period: The period 36 months prior to the index date. Data within 36 months prior to the index date will be used to assess baseline characteristics.
• Post-index period: The period 180 days after the index date

• Study Type: Observational
• Enrollment (Actual): 9456

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • East Hanover, New Jersey, United States, 07936-1080
      • Novartis Pharmaceuticals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with wet AMD who initiated brolucizumab were analyzed in this study.

Description

Inclusion Criteria:

1. ≥1 Healthcare Common Procedure Coding System (HCPCS) code (J code) or EMR note for treatment with brolucizumab during the index period (date of earliest code or EMR note = index date)
2. ≥18 years old on the index date
3. ≥1 Current Procedural Terminology (CPT) code for intravitreal administration on the index date

4. ≥1 International Classification of Diseases, Clinical Modification-9/10 (ICD-9/10) code for wet AMD in the 36 months prior to or on the index date

   o Note: Off-label use of brolucizumab is not expected given payer access restrictions in the US.

5. ≥1 follow-up visit after the index date
6. ≥1 VA assessment on the index date or within 90 days prior to the index date

Exclusion Criteria:

1. Use of brolucizumab prior to 10/8/2019 (e.g. clinical trials)
2. Unknown laterality of the index eye on the index date

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Brolucizumab; Participants received brolucizumab injection during the index period	Drug: Brolucizumab; Participants received brolucizumab injection during the index period; Other Names: BEOVU®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient eyes with an Intraocular Inflammation (IOI) event during the first 6 months	To assess IOI events observed after starting treatment with brolucizumab	Up to 6 months post brolucizumab injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age	Age information was reported	At the brolucizumab index date defined as the date of first brolucizumab injection
Gender information	Gender information was reported	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of patients at various Patient Region	Patient regions: Northeast, Midwest, South, West, Unknown	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of patients with Insurance type	Insurance type: Medicare, Medicare Advantage, Medicaid, Commercial, Government, Military, No Insurance, Miscellaneous, Unknown	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of patients with Laterality of wet Age-related macular degeneration (AMD)	Laterality of wet AMD: Unilateral, Bilateral	At the brolucizumab index date defined as the date of first brolucizumab injection
Race/Ethnicity of the participants (patient level and eye level)	Caucasian, Black or African American, Asian, Other, Unknown	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of eyes with the concurrent eye disease	Types of concurrent eye diseases: ▪ Cataracts; Posterior vitreous detachment; Puckering of macula; Macular hole; Vitreomacular traction; Glaucoma; Amblyopia; Papillitis; Ischemic optic atrophy; Diabetic retinopathy; Diabetic macular edema; Hypertensive retinopathy; Pathologic myopia; RAO; RO; RV; Vitritis; Endophthalmitis; Uveitis; Choroidal neovascularization (due to causes other than AMD, if possible, to determine); IOI	Within 180 days prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with cataract status	Types: phakic, pseudophakic, aphakic	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with Concomitant ocular medications	Types: Corticosteroids; Prednisone; Prednisolone acetate; Difluprednate; Biologics; Cyclosporine; Methotrexate; Ganciclovir; Acyclovir; Trifluridine; Rituxan	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with the history of ocular inflammation	The following categories were reported: No history of inflammation; History of any ocular inflammation; History of severe ocular inflammation; History of anterior inflammation; History of posterior inflammation; History of IOI or endophthalmitis due to infections and other underlying disease (separate category)	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with prior Intraocular Inflammation (IOI) and/or prior Retinal vascular occlusion (RO)	Included history of ocular inflammation or occlusion	12 months prior to the index date ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with the Provider specialty	The following types were included: Retina specialist, General ophthalmologist, Non-retina specialist, unknown	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of patient eyes with the previous ocular surgeries or procedures	The following categories were included: Laser therapy; Laser coagulation; Photodynamic therapy; IOP lowering surgeries (lasers, glaucoma filtering, non-filtering glaucoma); Cataract surgery; Iridotomy; Intraocular or refractive surgery (almost all IOP & cataract surgeries); Previous penetrating keratoplasty, vitrectomy, or ocular radiation; Previous panretinal photocoagulation; Previous submacular surgery, other surgical intervention or laser treatment for AMD	6 months prior to the index date ( index date defined as the date of first brolucizumab injection)
Number of eyes treated with brolucizumab	The following types were included: OD [eye, right], OS [eye, left], Unspecified, Unilateral, Bilateral)	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of patient eyes with Visual Acuity (VA) reading	The following categories were included: Snellen: 20/10, 20/12-20/20, 20/25-20/40, 20/50-20/160, ≤20/200; Approximate ETDRS letters	At the brolucizumab index date defined as the date of first brolucizumab injection with lookback of 365 days
Number of patient eyes with Anti-VEGF treatment-naive vs prior-treated	Anti-VEGF treatment-naive vs prior-treated were measured at the eye level	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of patient eyes with the prior treatment status	The following types were included: off-label bevacizumab, ranibizumab, aflibercept, unknown, treatment-naive	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of different prior anti-VEGF agents	The following categories were measured at the eye level: 0, 1, 2, ≥3	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Number of prior anti-VEGF injections	Total, per anti-VEGF agent were measured at the eye level); Continuous; Categorical: <6, 6 to <12, 12 to <24, ≥24	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Duration of last anti-VEGF treatment	Total, per anti-VEGF agent; will be measured at the eye level; All anti-VEGFs i. Continuous ii. Categorical: <6, 6 to <12, 12 to <24, ≥24 months; Specific anti-VEGF iii. Continuous iv. Categorical: <6, 6 to <12, 12 to <24, ≥24 months	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Time since wet Age-related macular degeneration (AMD) diagnosis	Patients were measured at the eye level	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Time since any Age-related macular degeneration (AMD) diagnosis	Patients were measured at the eye level	36-month period prior to the index date (inclusive of the index date) ( index date defined as the date of first brolucizumab injection)
Time from last anti-VEGF injection to index date (among switchers)	The following categories were measured: Continuous (days); Categorical (0-30, 31-60, 61-90, 91+ days)	At the brolucizumab index date defined as the date of first brolucizumab injection
Number of ocular adverse events (AEs)	To assess the incidence of ocular AEs among patients treated with brolucizumab	Post-index period defined as the 180 days following therapy initiation, excluding index date

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CRTH258AUS15 from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 3, 2020
• Primary Completion (ACTUAL): December 15, 2020
• Study Completion (ACTUAL): December 15, 2020

Study Registration Dates

• First Submitted: October 5, 2021
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (ACTUAL): October 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 19, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: visual acuity; intravitreal injection,; Brolucizumab,; neovascular age-related macular degeneration,
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: CRTH258AUS15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No