Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER.

OBJECTIVE: To compare the efficacy of brolucizumab and aflibercept treatment in reducing the maximum thickness of pigment epithelial detachments (PEDs) and sub-retinal pigment epithelium (sub-RPE) fluid in patients with neovascular age-related macular degeneration in the HAWK and HARRIER studies. DESIGN: HAWK and HARRIER were 96-week, prospective, randomized, double-masked, controlled, multicenter studies. PARTICIPANTS: A total of 1775 patients across 11 countries were included in the HAWK study, and 1048 patients across 29 countries were included in the HARRIER study. INTERVENTION: After 3 monthly loading doses, brolucizumab-treated eyes received injections every 12 weeks or every 8 weeks if disease activity (DA) was detected. Aflibercept-treated eyes received fixed 8-week dosing. MAIN OUTCOME MEASURES: Maximum thickness of PEDs and sub-RPE fluid across the macula were assessed at baseline through week 96 in the brolucizumab- and aflibercept-treated patients and in the patient subgroups with DA at week 16 (matched in terms of injection number and treatment interval). RESULTS: At week 96, there were greater mean percentage reductions from baseline in maximum thickness of both PEDs and sub-RPE fluid in brolucizumab-treated patients vs. aflibercept-treated patients (PED: 19.7% [n = 336] vs. 11.9% [n = 335] in HAWK; 29.5% [n = 364] vs. 18.3% [n = 361] in HARRIER. Sub-RPE fluid: 75.4% vs. 57.3% in HAWK; 86.0% vs. 76.3% in HARRIER). A similar trend in mean percentage reductions was observed in patients with DA at week 16. CONCLUSIONS: This analysis shows that brolucizumab achieved greater reductions in PEDs and sub-RPE fluid thickness than aflibercept in HAWK and HARRIER. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02307682 (HAWK) and NCT02434328 (HARRIER). FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Clinical Outcomes and Experiences with Prefilled Syringes Versus Vials for Intravitreal Administration of Anti-VEGF Treatments: A Systematic Review.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) agents have been the standard treatment for retinal diseases for almost two decades. These treatments are administered via intravitreal injection using single-use vials or prefilled syringes (PFS). In this systematic review, we evaluate health care resource use and clinical outcomes and experiences with PFS for intravitreal injection of anti-VEGF treatments. METHODS: MEDLINE, EMBASE, and The Cochrane Library were searched from January 1, 2015 to February 8, 2024 to identify literature reporting outcomes regarding procedural efficiency, health care resource use, patient and clinician experiences, and safety for currently approved anti-VEGFs (ranibizumab, aflibercept, brolucizumab) administered using PFS. Comparators were vial-based injections of the same anti-VEGFs. RESULTS: A total of 36 publications met the criteria for inclusion in the systematic literature review; the majority were non-randomized studies, with a small number of reviews, case series, survey studies, and opinion articles. Publications reported that preparation times were significantly shorter for PFS (40.3-57.9 s) versus vials (ranibizumab, 62.8-98.0 s; aflibercept, 71.9-79.5 s), with no differences in product stability between PFS and vials. Clinicians expressed a preference for PFS and thought PFS were faster, easier to use, and had increased safety versus vials. Publications consistently reported significantly lower rates of endophthalmitis per injection with PFS versus vials (ranibizumab PFS, 0-0.02%; aflibercept PFS, 0.01-0.02%; ranibizumab vial, 0.02-0.05%; aflibercept vial, 0.02-0.06%). Four publications reported increased rates of transient vision loss after aflibercept PFS injection versus vial-based injection. No publications reported outcomes regarding health care resource use or patient experiences. CONCLUSION: The available literature supports the increased procedural efficiency of PFS versus vial-based intravitreal injection of anti-VEGFs. PFS are positively perceived by clinicians and have a safety benefit in the form of a decreased risk of endophthalmitis versus vials.

Anti-vascular endothelial growth factor (VEGF) drugs, given by injection into the eye, are commonly used to treat diseases that affect the back of the eye (the retina). Anti-VEGF drugs are provided in small containers (vials) or in syringes that are already filled with the drug (prefilled syringes). When someone is treated with an anti-VEGF drug from a vial, the drug must first be taken from the vial using a needle and syringe, and then injected. When someone is treated with an anti-VEGF drug from a prefilled syringe, the drug is injected directly from the prefilled syringe, i.e., there are fewer steps involved when a prefilled syringe is used. We searched the medical literature to see if there were differences in clinical outcomes and experiences between prefilled syringes and vials when used to inject anti-VEGF drugs. Clinicians spent about 50% less time getting ready for injections when prefilled syringes were used than when vials were used. Clinicians also preferred to use prefilled syringes than vials for injecting anti-VEGF drugs. Clinicians reported that prefilled syringes were easier to use, faster, and safer than vials. Patients who were given injections from prefilled syringes had a lower rate of infection of the inside of the eye (endophthalmitis) than patients who were given injections from vials. These results indicate that using prefilled syringes for injecting drugs into the eye can improve efficiency at ophthalmology clinics and improve safety for patients.

PIGMENT EPITHELIAL DETACHMENT THICKNESS AND VARIABILITY AFFECTS VISUAL OUTCOMES IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To evaluate the impact of pigment epithelial detachment (PED) thickness (i.e., height) and thickness variability on best-corrected visual acuity outcomes in patients with neovascular age-related macular degeneration in the Phase 3 HAWK and HARRIER trials. METHODS: Optical coherence tomography images from the pooled brolucizumab 6 mg and aflibercept 2 mg arms were analyzed for the maximum PED thickness across the macula at baseline through to week 96. Best-corrected visual acuity outcomes were compared in patients with different PED thickness and variability cut-off thresholds. RESULTS: Greater PED thickness at baseline or at week 12 was associated with lower mean best-corrected visual acuity gain from baseline to week 96 (baseline PED ≥200 µ m: +4.6 letters; <200 µ m: +7.0 letters; week 12 PED ≥100 µ m: +5.6 letters; <100 µ m: +6.6 letters). Eyes with the largest PED thickness variability from week 12 through week 96 gained fewer letters from baseline at week 96 (≥33 µ m: +3.3 letters; <9 µ m: +6.2 letters). Furthermore, increased PED thickness at week 48 was associated with higher prevalence of intraretinal and subretinal fluid. CONCLUSION: In this treatment-agnostic analysis, greater PED thickness and PED thickness variability were associated with poorer visual outcomes in patients with neovascular age-related macular degeneration and greater neovascular activity.

Comparative assessment of subretinal hyper-reflective material in patients treated with brolucizumab versus aflibercept in HAWK and HARRIER.

PURPOSE: Post hoc analysis of the phase III HAWK and HARRIER studies to compare the reductions in subretinal hyper-reflective material (SHRM) thickness following brolucizumab 6 mg or aflibercept 2 mg treatment and to assess SHRM thickness and thickness variability as a potential biomarker of visual outcomes in patients with neovascular age-related macular degeneration (nAMD). METHODS: Optical coherence tomography images from the brolucizumab (n=700) and aflibercept (n=696) arms were analysed for the maximum SHRM thickness across the macula over 96 weeks. In a pooled treatment-agnostic analysis, the effect of week 12 SHRM thickness and SHRM thickness variability on best-corrected visual acuity (BCVA) through week 96 were also assessed. RESULTS: Brolucizumab was associated with numerically higher percentage reductions from baseline in SHRM thickness versus aflibercept in all patients (week 96: 54.4% vs 47.6%, respectively) and also in the matched subgroups with disease activity at week 16 (week 96: 51.6% vs 33.8%, respectively). In eyes with lower SHRM measurements at week 12, mean BCVA gains from baseline were higher at week 96 (<200 µm, +6.47 Early Treatment Diabetic Retinopathy Study letters; ≥200 µm, +3.10 letters). Eyes with the lowest SHRM thickness variability from week 12 to week 96 showed the greatest mean BCVA gains from baseline (week 96: <12 µm, +7.42 letters; >71 µm, -2.95 letters). CONCLUSIONS: In HAWK and HARRIER, greater reductions in maximum SHRM thickness from baseline were observed with brolucizumab compared with aflibercept. Furthermore, the data suggest that SHRM thickness postloading and SHRM thickness variability over time are biomarkers for visual outcomes in patients with nAMD.

Treatment patterns in patients with age-related macular degeneration and diabetic macular edema: A real-world claims analysis in Dubai.

OBJECTIVES: To characterize the pattern of approved anti-vascular endothelial growth factor (VEGF) treatments among patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in the United Arab Emirates (UAE). METHOD: This was a retrospective, nonrandomized, observational cohort analysis of the Dubai Real-world Claims Database with a 360-day follow-up period. Adult patients diagnosed with nAMD or DME treated with ranibizumab or aflibercept for the first time were included. The primary objective was to evaluate anti-VEGF treatment patterns with respect to the proportion of patients receiving ranibizumab and aflibercept for nAMD and DME separately. RESULTS: Of the 451 patients included in the final study cohort, 83.6% and 16.4% had a diagnosis of DME (ranibizumab: 48.5%; aflibercept: 51.5%) and nAMD (ranibizumab: 40.5%; aflibercept: 59.5%), respectively, at baseline. Treatment frequency of ranibizumab/aflibercept was similar for nAMD (mean: 2.4/2.9 injections; p = 0.2389) with fewer injections in the ranibizumab cohort for DME (mean: 1.9/2.5 injections; p = 0.0002). Most patients received ≤3 anti-VEGF injections during the 360-day follow-up period. The time between consecutive treatments was large (nAMD: 73.6 days/10.5 weeks; DME: 80.5 days/11.5 weeks). Approximately 10%-13.5% of patients switched their anti-VEGF therapy. Most patients (83.8%) had a diabetes diagnosis during the follow-up period. CONCLUSIONS: This real-world study provides an initial understanding of anti-VEGF treatment patterns in patients with nAMD and DME in the UAE. Treatment frequency of the 2 anti-VEGF agents assessed was similar in both patient populations. Both treatments were infrequently administered with large dosing intervals.