Literature review and proposal of best practice for ophthalmologists: monitoring of patients following intravitreal brolucizumab therapy

Abstract

Brolucizumab is a novel humanised, single-chain, variable fragment inhibitor of Vascular Endothelial Growth Factor-A for the treatment of neurovascular age-related macular degeneration. Brolucizumab gained US Food and Drug Administration and European Medicines Agency approval following the Phase III HAWK (NCT02307682) and HARRIER (NCT02434328) trials which compared brolucizumab with aflibercept, presenting a tolerable safety and favourable efficacy profile. The mean change (least squares [LS] mean ± standard error) in best-corrected visual acuity letters from baseline to week 96 in the HAWK trial was 5.9 ± 0.78 for brolucizumab (6 mg) versus 5.3 ± 0.78 for aflibercept, and in the HARRIER trial, 6.1 ± 0.73 (6 mg) for brolucizumab (6 mg) and 6.6 ± 0.73 for aflibercept. Within both trials, greater reductions were noted in the central subfield thickness from baseline to week 96 in the brolucizumab (6 mg) groups versus the aflibercept group. Subsequent post-marketing reports detailed intraocular inflammation (IOI) after brolucizumab treatment and in response an independent safety review committee conducted a post hoc data review. While comparable, the rate of brolucizumab-associated IOI was higher in the post hoc analysis than the trials (4.6% and 4.4%, respectively). Findings from trials and real-world data indicate there may be pre-defining risk factors that predispose patients to IOI following brolucizumab treatment. With a thorough understanding of IOI classification and best practice management, ophthalmologists can use brolucizumab confidently and, should a case arise, they should act quickly to prevent vision loss. Herein, we provide information and guidance to support clinical decision-making related to brolucizumab use.

Brolucizumab for the Treatment of Degenerative Macular Conditions: A Review of Clinical Studies

“…To date, brolucizumab has been only approved by the FDA and the EMA for the treatment of nAMD, based on the findings from the HAWK and HARRIER studies. 53 , 79 Except from efficacy, these Phase III clinical trials concluded that brolucizumab demonstrated an overall well-tolerated safety profile, similar to aflibercept. 53 Decreased visual acuity, conjunctival and retinal haemorrhage, vitreous floaters, eye pain, dry eye, cataract, and vitreous detachment were among the ocular adverse events (AEs) observed in <5% of the participants.…”

“… 81 Aiming to determine whether these post-marketing data indicated a safety signal for the drug, Novartis commissioned an external, independent safety review committee (SRC) to conduct a thorough review of the evidence from the phase III studies and evaluate the post-marketing reports. 79 , 81 …”

“… 81 However, the proportion of eyes that lost ≥15 ETDRS letters was comparable between the brolucizumab (7.4%) and aflibercept (7.7%) treatment arms through week 96. 79 , 81 …”

“…Although the risk of inflammation is highest soon after the intravitreal injection is administered, ophthalmologists should apparently be vigilant for more than 12 months postinjection because inflammatory episodes may still occur within this period. 79 , 81 …”

“…Although the sample size was small, their results were comparable to those presented in the HAWK trial. 79 , 81 …”