Off-label intravitreal brolucizumab for recalcitrant diabetic macular edema: A real-world case series

Abstract

Purpose To report the efficacy of intravitreal injection (IVI) of brolucizumab for recalcitrant diabetic macular edema (DME) in a real-world setting. Observations This was a single-center, prospective uncontrolled non-randomized case series. Three eyes with recalcitrant DME, who have received a minimum of ten intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, underwent IVI brolucizumab and were followed-up for minimum of 16 weeks. Patients underwent best-corrected visual acuity (BCVA) testing, ophthalmic examination, and optical coherence tomography at baseline and all the scheduled follow-up visits (Weeks 4, 8, 12, and 16). All three patients demonstrated notable improvement in BCVA and reduction in the fluid on SD-OCT lasting up to week 12. At week 16, all three eyes maintained the visual acuity gains. However, early increase in fluid was noted in all the three cases, for which second dose of IVI brolucizumab was planned. No ocular or systemic adverse events were noted in any of the cases. Conclusions and Importance In this real-world case series, treatment with IVI brolucizumab exhibited excellent visual acuity outcomes lasting up to 16 weeks for the treatment of recalcitrant DME. Single dose IVI brolucizumab achieves good anatomical improvement based on SD-OCT persisting up to 12 weeks, followed by early recurrence of fluid at week 16. The results did not show any ocular or systemic safety concerns for IVI brolucizumab.

Recommendations for Off-Label Drug Use in Ophthalmology in China: A Clinical Practice Guideline

“…Since the outbreak of the COVID-19 pandemic, there have been multiple attempts to use medications already approved or developed for indications, which are repurposed for the treatment of COVID-19 based on the assumptions of safety and efficacy with short approval time ( Guy et al, 2020 ; Shaffer, 2020 ). According to the literature review, off-label drugs used in ophthalmology are frequent, and they mainly include anti-vascular endothelial growth factors used in neovascularization disease ( Dascalu et al, 2016 ; Bro et al, 2020 ; Chakraborty et al, 2021 ; Panigrahi, 2021 ). Nevertheless, in general, as well as in the treatment of ocular surface diseases in particular, we benefit significantly from the off-label use of drugs that are first developed for other indications ( Novack, 2021 ).…”

Intravitreal Brolucizumab for Choroidal Neovascularization Associated to Angioid Streaks

“…Brolucizumab is a single-chain humanized antibody fragment with a relatively small molecular size and a weight of only 26 kDa [ 13 ]. Brolucizumab's effective molar dose is 12-fold greater than aflibercept and 22-fold more than ranibizumab due to its low molecular weight, which is 1/1.8 of that of ranibizumab and 1/4 of that of aflibercept [ 13 ].…”

“…The most recently FDA-approved treatment for neovascular age-related macular degeneration (nAMD) is the brolucizumab (Beovu ®; Novartis, Basel, Switzerland) molecule [ 13 ]. It has been successfully used in the management of recalcitrant diabetic macular edema (DME) as an off-label medication [ 13 ].…”

Current and Novel Therapeutic Approaches for Treatment of Diabetic Macular Edema

“…A brolucizumab dose of 6 mg produces a molar dosage that is approximately 11 times that of aflibercept (2 mg) and 22 times that of ranibizumab (0.5 mg) [ 64 ]. A study examining the off-label use of brolucizumab for three patients with recalcitrant DME found that, at 16 weeks, all three demonstrated notable improvement in BCVA (20/40 to 20/25) and a reduction in fluid on SD-OCT [ 93 ]. Results 52 weeks into the prospective, randomized, phase III clinical study in DME, KITE, which aimed to confirm brolucizumab (6 mg) noninferiority to aflibercept (2 mg), indicated that brolucizumab may provide robust vision gains and superior anatomic outcomes with q12w treatment intervals in more than 50% of patients with DME (10.6 letters for brolucizumab vs. 9.4 letters for aflibercept, p < 0.001) [ 93 , 94 , 95 ].…”