Anti‐drug antibodies to brolucizumab and ranibizumab in serum and vitreous of patients with ocular disease

Abstract

Purpose Postapproval reports of intraocular inflammation (IOI) and occlusive retinal vasculitis following intravitreal brolucizumab are accumulating. A role of anti‐drug antibodies (ADAs) to brolucizumab is under current scientific discussion. The purpose of the present study was to measure brolucizumab ADAs in a cross‐sectional ophthalmic patient population and to compare the occurrence of brolucizumab ADAs with that of ranibizumab ADAs. Methods One hundred and ninety‐two serum samples and 54 vitreous samples were collected from patients with a range of eye diseases including neovascular age‐related macular degeneration (AMD), diabetic retinopathy, retinal vein occlusion, cataract, glaucoma, dry eye disease, macular hole, epiretinal membranes and intraocular lens (IOL) dislocation. Serum and vitreous samples were analysed for immune globuline (Ig) G ADAs to brolucizumab and ranibizumab using indirect enzyme‐linked immunosorbent assay (ELISA). Optical Density (OD) was read at 450 nm (wavelength correction at 550 nm) for ADA level measurements. Results Presence of brolucizumab ADAs was observed in patients with and without prior brolucizumab exposure. Both the frequency of notable ADA signals (OD > 0.1) and the mean ADA signal in serum samples were higher for brolucizumab than for ranibizumab. Two patients who experienced severe IOI and occlusive retinal vasculitis following intravitreal brolucizumab had high brolucizumab ADA serum levels. In one of these two patients, high brolucizumab ADA levels were also found in vitreous. Another patient developed moderate IOI without retinal vasculitis in the presence of low brolucizumab ADA serum levels. Overall, notable brolucizumab ADA levels were less frequent in vitreous than in the corresponding serum samples but with a tendency for higher prevalence in vitreous from patients with diabetic retinopathy. Conclusion Brolucizumab ADAs occur with significant prevalence in a typical ophthalmic patient population and may represent a risk factor for IOI and occlusive retinal vasculitis following brolucizumab.

Retinal Vasculitis After Intravitreal Pegcetacoplan: Report From the ASRS Research and Safety in Therapeutics (ReST) Committee

“…[15][16][17][18] In the case of brolucizumab, much higher rates of anti-drug antibodies (ADAs) at baseline as well as induced or boosted during clinical trials have been reported compared with ranibizumab and aflibercept. [19][20][21][22] It is possible that the higher rates of preexisting and treatment-emergent anti-brolucizumab antibodies may help explain the higher rates of inflammation with brolucizumab than with the other anti-VEGF drugs; however, it is unclear what their role is in cases of intraocular inflammation. Of note, with pegcetacoplan, the incidence of ADAs was relatively low in clinical trials; they were detected in 2.5% to 4% of participants in the OAKS and DERBY trials.…”

Immunogenicity With Ranibizumab Biosimilar SB11 (Byooviz) and Reference Product Lucentis and Association With Efficacy, Safety, and Pharmacokinetics

“…In the trial reported here, no IOI was associated with retinal vasculitis. Busch and colleagues reported higher ADA-positivity rates in participants treated with brolucizumab than in those treated with RBZ (18.2% vs 2.6%). Nevertheless, high ADA levels did not necessarily result in IOI.…”

Feasibility demonstration of a device for vitreous liquid biopsy incidental to intravitreal injection

“…Analysis of the biopsy has potential to guide follow up care. An analysis panel consisting of the concentration of drug [26], drug target [27], downstream proteins [28], proteins in parallel disease processes [29], anti-drug antibodies [30], or other analytes may provide clinicians with an useful supplement to structural imaging as a biomarker to help select appropriate therapy and adjust dose timing [31]. Within research settings, analysis of a liquid biopsy has potential to increase the probability of clinical trial success [32] and identify targets for new therapeutics [33].…”