Brolucizumab and immunogenicity

Sharma, Ashish; Kumar, Nilesh; Parachuri, Nikulaa; Sharma, Rohini; Bandello, Francesco; Kuppermann, Baruch D.; Loewenstein, Anat

doi:10.1038/s41433-020-0853-9

Cited by 42 publications

(49 citation statements)

References 10 publications

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“…The incidence of IOI in the HAWK and HARRIER studies was 4% for brolucizumab as compared to 1% for aflibercept [37]. The American Society of Retinal Specialists (ASRS) had issued an alert in February 2020 after 14 cases of retinal vasculitis, of which 11 were occlusive vasculitis, were reported after use of IVI brolucizumab [38]. We found a non-infectious vitritis rate of 0.02% (2/9406) with Razumab, similar to that reported with other anti-VEGF drugs (0.05-2.9%) [16,17] and lower than that (0.3%) attributed to SB11 [34].…”

Section: Discussionmentioning

confidence: 99%

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Chakraborty¹,

Stewart

Sheth

et al. 2021

Ophthalmol Ther

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Introduction To assess the safety profile of the intravitreal ranibizumab biosimilar molecule, Razumab ® (Intas Pharmaceuticals, Ahmedabad, India) in chorioretinal disorders under real-world conditions. Methods This was a multicenter, retrospective chart review which included patients from 15 centers receiving intravitreal Razumab (IVRz) injections from 2016 to 2020. Patient demographics, ocular examination data, and detailed safety information regarding serious adverse events (SAE) or serious adverse drug reactions (sADR), and non-serious AEs (nsAE) or non-serious ADRs (nsADR) occurring within 1 month of IVRz injections were compiled. Results A total of 6404 eyes of 6404 patients received 9406 IVRz injections [mean (± SD) = 1.49 (± 0.63)] during 4.25 years. Adverse events were reported after 1978 injections (21.03%): 64.16% nsAE, 32.96% nsADR, 2.37% sADR, and 0.51% SAE. The most frequent adverse events were subconjunctival hemorrhage (8.2% of total injections), transient blurring of vision (6.5% of total injections), and mild ocular pain (5.27% of total injections). Serious ocular (31 cases with retinal pigment epithelial tears [0.33%], two cases of non-infectious vitritis [0.02%], and one case of endophthalmitis [0.01%]) and systemic (seven patients with non-fatal myocardial infarction [0.12%] and six patients with non-fatal cerebrovascular accident [0.09%]) adverse events were infrequent. Conclusion The study reports the largest pooled safety data on IVRz use in a real-world scenario. The results did not raise any new ocular or systemic safety concerns for the biosimilar agent, with the incidence and spectrum of adverse reactions similar to those reported with other anti-vascular endothelial growth factor (anti-VEGF) drugs. The real-world evidence suggests that IVRz is a safe anti-VEGF agent in the management of chorioretinal disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00345-2.

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Section: Discussionmentioning

confidence: 99%

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Chakraborty¹,

Stewart

Sheth

et al. 2021

Ophthalmol Ther

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“…An additional filtration step was then added to the manufacturing process, and endotoxin limits were corrected [ 43 , 44 ]. After these modifications, the rate of ocular inflammation was significantly reduced [ 45 ].…”

Section: Sterile Intraocular Inflammationmentioning

confidence: 99%

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Cox

Eliott

Sobrin

2021

JCM

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Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents is a commonly used therapy for numerous retinal diseases. The most commonly used of these medications are bevacizumab, ranibizumab, aflibercept, and brolucizumab. However, intravitreal administration of these agents is also associated with several inflammatory and non-inflammatory adverse events. The three inflammatory adverse events are sterile intraocular inflammation, brolucizumab-associated retinal vasculitis, and post-injection endophthalmitis. This narrative review summarizes the current literature regarding these conditions, including their epidemiology, presentation, management, outcomes, and pathogenesis. The inflammatory adverse events also share a number of overlapping features, which can make them difficult to discern from one another in a clinical context. This review discusses certain distinguishing features of these conditions that may aid providers in discerning between them and establishing the correct diagnosis.

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“…The small number and heterogeneity of cases to date has made clarifying a causative factor difficult. Several reports have postulated either a type III or type IV hypersensitivity reaction [ 38 , 79 ]. Type III hypersensitivity reactions have been known to occur due to intravascularly injected monoclonal antibodies [ 80 ].…”

Section: Immunology and Pathways Of Late Onset Inflammatory Vasculitismentioning

confidence: 99%

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review

et al. 2021

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Background Intraocular inflammation is an uncommon but potentially vision-threatening adverse event related to anti-VEGF therapy. This is of increasing importance given both the volume of injections performed, as well as the increased prevalence of inflammation seen with newer anti-VEGF agents. Brolucizumab, the newest anti-VEGF agent, has been associated with an inflammatory retinal vasculitis and the underlying mechanism is unclear. Reviewing potential mechanisms and clinical differences of intraocular inflammation may assist clinicians and scientists in reducing the risk of these events in the future. Observations Two types of inflammation are seen with intravitreal injections, acute onset sterile inflammation and delayed onset inflammatory vasculitis. Acute onset inflammation can be subcategorized into subclinical anterior chamber inflammation and sterile uveitis/endophthalmitis. Subclinical anterior chamber inflammation can occur at rates as high as 19% after intravitreal anti-VEGF injection. Rates of sterile uveitis/endophthalmitis range from 0.05% to 4.4% depending on the anti-VEGF agent. Inflammatory vasculitis is only associated with brolucizumab and occurred in 3.3% of injections according to the post hoc review of the HAWK/HARRIER data. In addition, silicone oil from syringes can induce immunogenic protein aggregates. Agitation of the syringe, freeze thawing, shipping and improper storage prior to injection may increase the amount of silicone oil released from the syringe. Conclusion The main factors which play a role in intraocular inflammation after anti-VEGF injection can be divided into three causes: patient-specific, medication-specific and delivery-specific. The majority of clinically significant inflammation seen after intravitreal injection is an acute onset inflammatory response with most patients recovering baseline VA in 3–5 weeks. The presence of pain, hypopyon, severe anterior chamber reaction, hyperemia and significant vision loss may help distinguish infectious from non-infectious etiologies of post injection inflammation. Avoiding temperature fluctuation, mechanical shock, agitation during transport and handling of syringes/drugs, and the use of SO-free syringes may help minimize intraocular inflammation. While a definitive mechanism has not yet been established, current knowledge of the clinical presentation and vitreous histopathology of brolucizumab-retinal vasculitis favors an auto-immune type IV hypersensitivity reaction.

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Brolucizumab and immunogenicity

Cited by 42 publications

References 10 publications

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Real-World Safety Outcomes of Intravitreal Ranibizumab Biosimilar (Razumab) Therapy for Chorioretinal Diseases

Inflammatory Complications of Intravitreal Anti-VEGF Injections

Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review

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