Bevacizumab in age-related macular degeneration: why an off-label treatment is the preferred therapy?

Age-related macular degeneration (AMD) is an ocular inflammatory diseases treated mainly by means of a bevacizumab (Avastin®) or ranibizumab (Lucentis®) intravitreal injection. Among these drugs, only ranibizumab has a specific therapeutic indication for AMD. Considering that, the off-label use on ophthalmic therapy seems to become a rule when it should be an exception. Furthermore, bevacizumab presentation consists of multi-dose vials although it does not contain preservatives in its formula. The current literature review aimed at assessing the risks for the patient related to the use of off-label indication and multi-dose vials on AMD treatment. Considering this, the proposal related to the Brazilian Public Consultation no.10, dated September 12, 2012, which proposes the Clinical Protocol and Therapeutic Guidelines for AMD treatment, was evaluated. This systematic review allowed to conclude that the bevacizumab off-label indication results in increased risks for the patient when compared to the product with specific therapeutic indication for AMD treatment (ranibizumab), especially referring to the significant raise in the adverse events. The risks for the patient related to the multi-dose vial use, referring to the microbiological stability and dose precision, were also made clear.

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PP-035 The treatment of submacular haemorrhage due to neovascular age related macular degeneration using intravitreal alteplase (rtPA): preparation and clinical outcomes of the off-label therapy

10.1136/ejhpharm-2017-000640.482 ◽

2017 ◽

Author(s):

E Malo ◽

F Marchesini ◽

R Tessari ◽

G Giovagnoni ◽

T Zuppini

Keyword(s):

Macular Degeneration ◽

Clinical Outcomes ◽

Age Related Macular Degeneration ◽

Off Label ◽

Age Related

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Off-label use of bevacizumab for wet age-related macular degeneration in Europe

Graefe s Archive for Clinical and Experimental Ophthalmology ◽

10.1007/s00417-019-04569-8 ◽

2019 ◽

Vol 258 (3) ◽

pp. 503-511

Author(s):

Tomas Bro ◽

Magdalena Derebecka ◽

Øystein Kalsnes Jørstad ◽

Andrzej Grzybowski

Keyword(s):

Macular Degeneration ◽

European Countries ◽

Age Related Macular Degeneration ◽

Off Label Use ◽

Off Label ◽

Age Related ◽

Governmental Institutions ◽

Very High ◽

Wet Amd ◽

Label Use

Abstract Purpose To analyse current off-label use of bevacizumab for wet age-related macular degeneration (AMD) in Europe. Methods The study was conducted as a combined survey and literature review. It included the 22 most populous countries in Europe. In each country, ophthalmologists with particular knowledge about off-label treatment responded to a questionnaire. Results Answers were obtained from twenty European countries. The off-label use of bevacizumab for wet AMD greatly differed between nations; the bevacizumab proportion varied from non-existent (0%) to very high (97%). There were also large disparities within single countries (e.g. 0–80%), which were attributable to differences in regional decision-making. Both governmental institutions and national ophthalmological societies expressed highly diverging opinions on the use of off-label treatment. Intravitreal administration of bevacizumab had been a matter of legal dispute in several countries. The question about responsibility for off-label therapy mainly remained unanswered. Conclusions There was a highly varying utilization of bevacizumab between European countries. Despite an intention of a consistent approach to medical regulations, Europe has not yet reached a professional or political consensus on the ophthalmic off-label use of bevacizumab.

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Off-Label Use of Bevacizumab for the Treatment of Age-Related Macular Degeneration

Drugs & Aging ◽

10.2165/00002512-200926040-00002 ◽

2009 ◽

Vol 26 (4) ◽

pp. 295-320 ◽

Cited By ~ 18

Author(s):

Focke Ziemssen ◽

Salvatore Grisanti ◽

Karl Ulrich Bartz-Schmidt ◽

Martin S. Spitzer

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Off Label Use ◽

Off Label ◽

Age Related ◽

Label Use

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Contextualising Single-Arm Ophthalmology Trials With Real-World Data: An Emulated Target Trial Comparing The Efficacy Of Interventions For Neovascular Age-Related Macular Degeneration

10.1101/2020.08.10.20171538 ◽

2020 ◽

Author(s):

Darren S Thomas ◽

Aaron Y. Lee ◽

Philipp L. Muller ◽

Roy Schwartz ◽

Abraham Olvera-Barrios ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Real World ◽

Age Related Macular Degeneration ◽

Target Trial ◽

Real World Data ◽

World Data ◽

Off Label ◽

Age Related ◽

Randomised Controlled

Methods of causal inference have shown promise in replicating randomised trials using real-world data recorded by Electronic Health Records (EHRs). We herein emulated a target trial on the intention-to-treat efficacy of off-label bevacizumab (q6w) pro re nata relative to fixed-interval aflibercept (q8w) for improving week-54 visual acuity of eyes affected by neovascular age-related macular degeneration. The bevacizumab arm (n 65) was taken from the ABC randomised controlled trial. A total of 4,471 aflibercept-treated eyes aligning with the ABC trial eligibility were identified from EHRs and synthetic control arms were created by emulating randomisation conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ -15 Early Treatment Diabetic Retinopathy Letters (ETDRS) letters at week 54; and a time-to-event analysis on achieving a change in visual acuity of ≥ 15, ≥ 10, and ≤ -15 ETDRS letters by week 54. Our findings suggest off-label bevacizumab to be neither non-inferior nor superior to licensed aflibercept. While being no substitute for randomised controlled trials, emulated target trials could aid the interpretation of single-armed trials.

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Off-Label Use of Bevacizumab in Age-Related Macular Degeneration: Protocol for a Systematic Review and Meta-Analysis

10.21203/rs.3.rs-377701/v1 ◽

2021 ◽

Author(s):

João Estarreja ◽

Carina Valente ◽

Carina Silva ◽

Pedro Camacho ◽

Vanessa Mateus

Keyword(s):

Systematic Review ◽

Macular Degeneration ◽

Vision Loss ◽

Meta Analysis ◽

Age Related Macular Degeneration ◽

Off Label Use ◽

Off Label ◽

Pharmacological Approach ◽

Age Related ◽

Label Use

Abstract Background: Age-related macular degeneration (AMD) is considered the leading cause of vision loss in elderly people. Taking into account the phenomenon of aging worldwide, the prevalence of AMD is expected to increase gradually in the future. AMD can be divided into early, intermediate and late stages, where early and intermediate are mainly asymptomatic and, late-stage can be classified in non-vascular AMD and vascular AMD. Current pharmacological treatment in vascular AMD is associated with the administration of anti-VEGF agents, such as ranibizumab, pegaptanib, and aflibercept. Additionally, it has been reported the off-label use of bevacizumab, commonly associated with oncology, in this condition through intravitreal administrations, demonstrating efficacy allied with a lower cost in comparison to other agents used, which makes it a new possible pharmacological approach. In this sense, this review aims to evaluate the off-label use profile of bevacizumab in the treatment of neovascular AMD. Methods/design: To identify and select relevant articles present in current literature, it will be developed a highly sensitive search strategy. To develop this search, it will be used MEDLINE via the Pubmed platform. It will be only considered clinical studies, where it is compared the use of bevacizumab with another pharmacological agent, such as ranibizumab, or even a placebo, in patients aged 50 years and older, diagnosed with vascular AMD.Discussion: This review will provide a synthesis of the current information and underlying evidence, about the influence of the off-label use of bevacizumab in this disease. Altogether, it will allow having a clearer vision on a new possible accepted pharmacological approach for the treatment of vascular AMD.Systematic review registration: The protocol for this review will be submitted and registered with the International Prospective Register of Systematic Reviews (PROSPERO).

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Age related macular degeneration (ARMD) – pathophysiological and clinical features and therapeutic concepts

Therapeutische Umschau ◽

10.1024/0040-5930.58.1.28 ◽

2001 ◽

Vol 58 (1) ◽

pp. 28-35 ◽

Cited By ~ 1

Author(s):

Ursula Körner-Stiefbold

Keyword(s):

Macular Degeneration ◽

Clinical Features ◽

Altersbedingte Makuladegeneration ◽

Age Related Macular Degeneration ◽

Genetische Faktoren ◽

Age Related ◽

Therapeutic Concepts

Die altersbedingte Makuladegeneration (AMD) ist eine der häufigsten Ursachen für einen irreversiblen Visusverlust bei Patienten über 65 Jahre. Nahezu 30% der über 75-Jährigen sind von einer AMD betroffen. Trotz neuer Erkenntnisse in der Grundlagenforschung ist die Ätiologie, zu der auch genetische Faktoren gehören, noch nicht völlig geklärt. Aus diesem Grund sind die Behandlungsmöglichkeiten zum jetzigen Zeitpunkt noch limitiert, so dass man lediglich von Therapieansätzen sprechen kann. Die derzeit zur Verfügung stehenden Möglichkeiten wie medikamentöse, chirurgische und laser- und strahlentherapeutische Maßnahmen werden beschrieben.

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