Brolucizumab-Associated Intraocular Inflammation Risk Requires Close Monitoring, Patient Education

Brolucizumab-associated intraocular inflammation (IOI) must be reported early to achieve successful outcomes, requiring patients to recognize IOI signs and clinics to conduct careful evaluations of patients using this treatment, especially during the loading phase, according to a study published in Ophthalmology Retina. “Most IOI-related events occurred in the loading phase, highlighting the need for patient education and ophthalmological monitoring during this period,” researchers explain. “Prompt discontinuation of brolucizumab and rapid treatment with corticosteroids resolved most IOI-related events.”

Between December 2020 and December 2022, the researchers presented interim descriptive insights regarding brolucizumab-associated intraocular inflammation events from the OCTOPUS (ClinicalTrials.gov Identifier: NCT04239027) and SWIFT (ClinicalTrials.gov Identifier: NCT04264819) trials. Both clinical trials were prospective phase IIIb single-arm, open-label, multicenter studies evaluating brolucizumab in both anti-VEGF naive (OCTOPUS) and pretreated (SWIFT) patients with neovascular age-related macular degeneration (nAMD).  

Of the 505 patients treated with brolucizumab (mean age, 76.9 years; 308 women), 53 patients (mean age, 76.0 years; 39 women) experienced at least 1 brolucizumab-associated intraocular inflammation adverse event in the study eye. The incidence of overall IOI-related adverse events was 10.5%; 7.1% for IOI only without retinal involvement and 3.4% for IOI with retinal involvement (2.0% with vasculitis, 1.4% with vascular occlusion with or without vasculitis).

Patients had a median of 2 (range: 1-6) injections before a brolucizumab-associated intraocular inflammation event, and the event occurred a median of 23 (range: 1-88) days following the last injection of brolucizumab.

The incidence of an IOI-related events was similar in naive and pretreated patients, the report shows.

At the onset of brolucizumab-associated intraocular inflammation, the most common reported symptoms were floaters (52.8%) and blurred or reduced vision (37.8%). A total of 86.8% of the adverse events were treated, 75.5% with topical corticosteroids, 28.3% with systemic corticosteroids and 26.8% with intraocular corticosteroids. 

No severe vision loss was reported for the 7 patients who experienced brolucizumab-associated intraocular inflammation.

At the time of IOI-related event resolution, the median best corrected visual acuity (BCVA) change from baseline was 1 letter (range: -74 to +32 letters), and 2 patients with occlusive vasculitis experienced BCVA loss ≥ 15 letters due to IOI-related AEs. 

All patients permanently discontinued treatment brolucizumab following the first brolucizumab-associated intraocular inflammation event.

“Patients with active IOI should not be treated with brolucizumab, as per the Summary of product characteristics. The decision to initiate brolucizumab treatment should follow careful consideration of the risk benefit ratio for that patient compared to alternative treatment (including consideration of the higher efficacy of brolucizumab on fluid dryness and disease control), based on the patient’s medical history and imaging workup to check for current signs of inflammation,” according to the researchers. “Prompt discontinuation of brolucizumab and rapid treatment with corticosteroids resolved most IOI-related events.” 

This study was limited because it was an interim analysis. 

Disclosure: This study was funded by Novartis SAS, France. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.