Product information and disease description Place of product in therapy Approaches to treatment Current treatment options and standard of care

Anti-VEGF monoclonal antibodies and antibody fragments

21 evidence topics · 13 sources

AAO Preferred Practice Pattern: anti-VEGF therapy as first-line treatment

“Intravitreal injection therapy using anti-vascular endothelial growth factor (VEGF) agents, which may or may not target other factors such as placental growth factor or angiopoietin-2, is the most effective way to manage neovascular AMD and is the first-line treatment.” (opens the source at this quote in a new tab)
“The choice of biologic product (reference, biosimilar, or interchangeable) should be that of the treating ophthalmologist and the patient whenever possible.” (opens the source at this quote in a new tab)
“Anti-VEGF therapies have become first-line therapy for treating and stabilizing most cases of neovascular AMD, and a Cochrane systematic review demonstrates the effectiveness of these agents to maintain VA.” (opens the source at this quote in a new tab)

NICE guideline NG82: anti-VEGF treatment and equivalence of agents

“Offer intravitreal anti-vascular endothelial growth factor (VEGF) treatment for late AMD (wet active) for eyes with visual acuity within the range specified in recommendation 1.5.6.” (opens the source at this quote in a new tab)
“Be aware that no clinically significant differences in effectiveness and safety between the different anti-VEGF treatments have been seen in the trials considered by the guideline committee.” (opens the source at this quote in a new tab)

Ranibizumab: MARINA sham-controlled phase 3 trial

“We enrolled 716 patients in the study.” (opens the source at this quote in a new tab)
“Mean increases in visual acuity were 6.5 letters in the 0.3-mg group and 7.2 letters in the 0.5-mg group, as compared with a decrease of 10.4 letters in the sham-injection group (P<0.001 for both comparisons).” (opens the source at this quote in a new tab)
“During 24 months, presumed endophthalmitis was identified in five patients (1.0%) and serious uveitis in six patients (1.3%) given ranibizumab.” (opens the source at this quote in a new tab)

Ranibizumab: ANCHOR trial versus verteporfin photodynamic therapy

“Mean visual acuity increased by 8.5 letters in the 0.3-mg group and 11.3 letters in the 0.5-mg group, as compared with a decrease of 9.5 letters in the verteporfin group (P<0.001 for each comparison).” (opens the source at this quote in a new tab)

Ranibizumab: FDA-labeled dosing intervals

“LUCENTIS 0.5 mg (0.05 mL of 10 mg/mL solution) is recommended to be administered by intravitreal injection once a month (approximately 28 days).” (opens the source at this quote in a new tab)
“Although not as effective, patients may also be treated with one dose every 3 months after 4 monthly doses. Compared with continued monthly dosing, dosing every 3 months over the next 9 months will lead to an approximate 5-letter (1-line) loss of visual acuity benefit, on average.” (opens the source at this quote in a new tab)

Bevacizumab (off-label): CATT comparison with ranibizumab

“In a multicenter, single-blind, noninferiority trial, we randomly assigned 1208 patients with neovascular AMD to receive intravitreal injections of ranibizumab or bevacizumab on either a monthly schedule or as needed with monthly evaluation.” (opens the source at this quote in a new tab)
“Bevacizumab administered monthly was equivalent to ranibizumab administered monthly, with 8.0 and 8.5 letters gained, respectively.” (opens the source at this quote in a new tab)
“The proportion of patients with serious systemic adverse events (primarily hospitalizations) was higher with bevacizumab than with ranibizumab (24.1% vs. 19.0%; risk ratio, 1.29; 95% confidence interval, 1.01 to 1.66), with excess events broadly distributed in disease categories not identified in previous studies as areas of concern.” (opens the source at this quote in a new tab)

Bevacizumab: off-label status and comparative efficacy in the AAO Preferred Practice Pattern

“Because preliminary reports appeared favorable, ophthalmologists began using intravitreal bevacizumab off-label to treat MNV.” (opens the source at this quote in a new tab)
“Presently, there does not appear to be a significant difference in efficacy between ranibizumab and bevacizumab.” (opens the source at this quote in a new tab)

Ranibizumab biosimilars

“There are several biosimilar ranibizumab molecules approved by the FDA and others are available in numerous other countries.” (opens the source at this quote in a new tab)
“There are no prospective long-term clinical data comparing ranibizumab biosimilars to ranibizumab.” (opens the source at this quote in a new tab)

Brolucizumab: HAWK and HARRIER phase 3 trials

“Patients (N = 1817) with untreated, active choroidal neovascularization due to age-related macular degeneration in the study eye.” (opens the source at this quote in a new tab)
“Greater than 50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing through Week 48 (56% [HAWK] and 51% [HARRIER]).” (opens the source at this quote in a new tab)
“Brolucizumab was noninferior to aflibercept in visual function at Week 48, and >50% of brolucizumab 6 mg-treated eyes were maintained on q12w dosing interval through Week 48.” (opens the source at this quote in a new tab)

Brolucizumab: retinal vasculitis and retinal vascular occlusion

“Retinal vasculitis and/or retinal vascular occlusion, typically in the presence of intraocular inflammation, have been reported with the use of BEOVU. These immune-mediated adverse events may occur following the first intravitreal injection. Discontinue treatment with BEOVU in patients who develop these events.” (opens the source at this quote in a new tab)
“The interval between two BEOVU doses during maintenance treatment should not be less than 8 weeks.” (opens the source at this quote in a new tab)

“Retinal vasculitis and IOI after brolucizumab IVI are characterized by variable occlusion of large or small retinal arteries, or both, and perivenular abnormalities. It may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss.” (opens the source at this quote in a new tab)

“After FDA approval, several cases of occlusive retinal vasculitis occurred after intravitreal brolucizumab injection.” (opens the source at this quote in a new tab)
“Although HAWK and HARRIER found a 2.1% incidence of retinal vasculitis with retinal vascular occlusion, postmarketing surveillance revealed a higher incidence of intraocular inflammation.” (opens the source at this quote in a new tab)

Brolucizumab: real-world incidence of intraocular inflammation

“The overall incidence of IOI and/or RO was 2.4% (255 of 10 654 eyes) and 2.4% (268 of 11 161 eyes) for the IRIS and Komodo groups, respectively, and RV and/or RO, 0.6% (59 of 10 654 eyes and 63 of 11 161 eyes), respectively.” (opens the source at this quote in a new tab)

Brolucizumab: MERLIN every-4-week dosing in persistent fluid

“Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab versus 6.1% (0% and 0.6%) for aflibercept.” (opens the source at this quote in a new tab)
“The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab versus aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks after the loading regimen.” (opens the source at this quote in a new tab)

Brolucizumab intraocular inflammation through 96 weeks: rates and reported event terms

“The incidence of ocular adverse events (AEs) was similar across all treatment groups in both HAWK and HARRIER up to week 96 (Table 1), with the exception of combined intraocular inflammation (IOI) (iritis and uveitis), which was higher in the brolucizumab 6 mg group of HAWK compared with the aflibercept group (4.7% vs. 0.6%).” (opens the source at this quote in a new tab)
“The AEs related to IOI reported in both studies were iritis, uveitis, anterior chamber cell, anterior chamber flare, anterior chamber inflammation, chorioretinitis, eye inflammation, iridocyclitis, keratic precipitates, retinal vasculitis, vitreous haze, and vitreitis; among these, the most frequently reported were iritis and uveitis.” (opens the source at this quote in a new tab)
“Compared with week 48, the incidence of these AEs from week 48 through week 96 was low, with additional cases in HAWK only (2 cases of iritis in the brolucizumab 3 mg group, 1 case in the brolucizumab 6 mg group, and 1 case in the aflibercept group and 1 case of uveitis in the brolucizumab 6 mg group).” (opens the source at this quote in a new tab)

“Disparities between treatment arms were observed in the rates of IOI, 4.4% with brolucizumab versus 0.8% with aflibercept, and of endophthalmitis, 0.7% with brolucizumab versus 0.1% with aflibercept.” (opens the source at this quote in a new tab)

Retinal artery occlusion with concomitant inflammation in HAWK and HARRIER

“More specifically in relation to ATEs, across both studies, 4 brolucizumab 3 mg patients and 6 brolucizumab 6 mg patients experienced a RAO event that was reported as a SAE in 3 patients in the brolucizumab 3 mg group and in 0 patients in the brolucizumab 6 mg group.” (opens the source at this quote in a new tab)
“All brolucizumab 6 mg patients and 1 of the brolucizumab 3 mg patients showed concomitant IOI either before or after the RAO event.” (opens the source at this quote in a new tab)
“Of patients with RAO and concomitant IOI, 6 patients lost letters (2, 15, 21, 55, 55, and 62 letters) and 1 patient gained 18 letters by the end of the study.” (opens the source at this quote in a new tab)

Endophthalmitis onset relative to injection in HAWK and HARRIER

“All but 1 of the brolucizumab endophthalmitis patients showed onset within 5 days from the last injection.” (opens the source at this quote in a new tab)
“The time to onset since the last active injection and the investigator assessments suggest that it is likely that these endophthalmitis cases were related to the injection procedure.” (opens the source at this quote in a new tab)

Interval from injection to diagnosis of brolucizumab-associated retinal vasculitis

“Retinal vasculitis and IOI on a per-eye basis were diagnosed at a mean of 30.3 days after brolucizumab IVI.” (opens the source at this quote in a new tab)
“The interval to seeking treatment with vasculitis after the second brolucizumab IVI seemed to be shorter, ranging between 7 and 26 days.” (opens the source at this quote in a new tab)
“In eyes with retinal vasculitis after the first brolucizumab injection, this presentation could be delayed as long as 8 weeks after the injection, making a direct toxic or infectious cause unlikely and pointing to an autoimmune event, possibly leading to ischemia as a more likely cause.” (opens the source at this quote in a new tab)

Clinical findings and visual acuity at diagnosis in the postmarketing case series

“All eyes showed vitreous cells or opacities, and most (11 eyes [73.3%]) showed anterior chamber cells.” (opens the source at this quote in a new tab)
“Fine, nongranulomatous keratic precipitates, conjunctival injection, and Descemet folds also were reported, and no case of hypopyon occurred in this series.” (opens the source at this quote in a new tab)
“Of the 15 eyes, 9 eyes (60%) lost 0.3 logMAR of VA or more (the equivalent of 3 lines or more of ETDRS acuity)” (opens the source at this quote in a new tab)
“Five eyes (33%) showed a VA of less than 20/200.” (opens the source at this quote in a new tab)

Management of brolucizumab-associated inflammation and examination before repeat injection

“Treatment consisted of corticosteroids administered by a variety of methods (topical, sub-Tenon, oral, intravitreal, or a combination thereof).” (opens the source at this quote in a new tab)
“Two patients underwent vitrectomy without improvement of vision.” (opens the source at this quote in a new tab)
“Repeat brolucizumab IVI is contraindicated in an eye with active IOI.” (opens the source at this quote in a new tab)
“It also means that a clinical examination should be considered (rather than using a direct-to-injection protocol) before repeating brolucizumab injections to confirm that no IOI or vasculitis are present.” (opens the source at this quote in a new tab)
“Continued examinations are indicated in eyes demonstrating solely IOI because the occlusive vasculitis may develop after the initial examination.” (opens the source at this quote in a new tab)

Prior anti-VEGF exposure and the reason for switching in affected eyes

“The number of previous anti-VEGF IVIs ranged between 2 and 80 in the affected eye before switching to brolucizumab.” (opens the source at this quote in a new tab)
“Nine patients were switched to brolucizumab for persistent intraretinal fluid, subretinal fluid (SRF), or both, and 3 patients were switched for potential increased durability of brolucizumab.” (opens the source at this quote in a new tab)

Inflammation with other approved anti-VEGF agents and the limits of incidence estimates

“Although IOI has been reported with the other FDA-approved anti-VEGF agents, most notably aflibercept, it typically is mild and sterile and resolves with corticosteroid eye drops.” (opens the source at this quote in a new tab)
“The incidence of retinal vasculitis cannot be ascertained because it is also not known how many injections of brolucizumab have been administered nationwide.” (opens the source at this quote in a new tab)

IVAN two-year comparison of ranibizumab with bevacizumab and of continuous with discontinuous dosing

“Between March 27, 2008, and Oct 15, 2010, we randomised 628 patients to ranibizumab or bevacizumab.” (opens the source at this quote in a new tab)
“Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (−1·63 letters, –4·01 to 0·75; p=0·18).” (opens the source at this quote in a new tab)
“It is now established that bevacizumab is not inferior to ranibizumab after 2 years of either continuous or discontinuous treatment with respect to visual acuity” (opens the source at this quote in a new tab)
“Safety was worse when treatment was administered discontinuously.” (opens the source at this quote in a new tab)