Can high-dose aflibercept effectively address unmet treatment needs in diabetic macular edema?
Diabetic macular oedema (DMO) has long been a challenging condition to manage, but the advent of intravitreal vascular endothelial growth factor inhibitor therapy has revolutionized treatment. Despite successful outcomes in clinical trials, real-world application has fallen short due to issues such as treatment burden. Researchers have turned to the concept of high-dose aflibercept as a potential solution to prolong the drug's therapeutic effects and reduce treatment frequency.
The PHOTON study, led by David Brown and team, presented a 48-week analysis comparing the efficacy and safety of intravitreal aflibercept at two different doses and dosing intervals for DMO treatment. The study included 658 DMO patients, with results indicating that aflibercept 8 mg dosed every 12 or 16 weeks was non-inferior to the standard 2 mg dose given every 8 weeks. Notably, patients on the higher dosage regimen required fewer injections over the study period, demonstrating the potential for extended durability and reduced treatment burden.
This study's findings are particularly significant in light of the challenges posed by treatment adherence in DMO patients. The LANDSCAPE study in France revealed that less than half of patients remained under treatment a year after initiation, emphasizing the importance of strategies to increase durability and reduce the frequency of injections. The study also addressed concerns about the potential impact of higher drug volumes on intraocular pressure, noting that the injection volume increase from 0.05 mL to 0.07 mL did not lead to significant pressure rises immediately post-injection.
While randomized clinical trials like PHOTON are crucial for establishing treatment efficacy and safety, real-world evidence is essential to confirm the durability of new treatment approaches in routine clinical practice. The study design's focus on comparing the high-dose aflibercept to the standard 2 mg dose may limit its ability to capture the full potential of the new regimen, especially considering the evolving trend towards treat-and-extend dosing strategies in DMO management.
In terms of diabetic retinopathy severity score improvements, aflibercept 8 mg dosed every 12 weeks demonstrated non-inferiority to the standard 2 mg dose every 8 weeks, while the 16-week interval did not meet the same criteria. The study authors highlighted baseline differences in retinopathy severity among groups as a potential factor influencing these outcomes, suggesting that undertreatment in certain subgroups may have affected the results.
One notable limitation of the PHOTON study was the lack of control over the double-masked procedure due to different drug volume vials between groups. While this may raise concerns about bias, the study's blind measurement of visual and anatomical outcomes helped mitigate this issue. Additionally, the use of non-prefilled packaging for aflibercept 8 mg vials raises considerations around the risk of endophthalmitis compared to prefilled syringes, a factor that clinicians will need to weigh against the benefits of extended durability.
In conclusion, the PHOTON study's results suggest that high-dose aflibercept could offer a viable solution to address treatment burden in DMO patients. With promising short-term outcomes indicating extended durability and similar safety profiles to standard dosing, further analysis at 96 weeks will be crucial to confirm these findings and establish the long-term benefits of this treatment approach.
(Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02760-5/fulltext)
The PHOTON study, led by David Brown and team, presented a 48-week analysis comparing the efficacy and safety of intravitreal aflibercept at two different doses and dosing intervals for DMO treatment. The study included 658 DMO patients, with results indicating that aflibercept 8 mg dosed every 12 or 16 weeks was non-inferior to the standard 2 mg dose given every 8 weeks. Notably, patients on the higher dosage regimen required fewer injections over the study period, demonstrating the potential for extended durability and reduced treatment burden.
This study's findings are particularly significant in light of the challenges posed by treatment adherence in DMO patients. The LANDSCAPE study in France revealed that less than half of patients remained under treatment a year after initiation, emphasizing the importance of strategies to increase durability and reduce the frequency of injections. The study also addressed concerns about the potential impact of higher drug volumes on intraocular pressure, noting that the injection volume increase from 0.05 mL to 0.07 mL did not lead to significant pressure rises immediately post-injection.
While randomized clinical trials like PHOTON are crucial for establishing treatment efficacy and safety, real-world evidence is essential to confirm the durability of new treatment approaches in routine clinical practice. The study design's focus on comparing the high-dose aflibercept to the standard 2 mg dose may limit its ability to capture the full potential of the new regimen, especially considering the evolving trend towards treat-and-extend dosing strategies in DMO management.
In terms of diabetic retinopathy severity score improvements, aflibercept 8 mg dosed every 12 weeks demonstrated non-inferiority to the standard 2 mg dose every 8 weeks, while the 16-week interval did not meet the same criteria. The study authors highlighted baseline differences in retinopathy severity among groups as a potential factor influencing these outcomes, suggesting that undertreatment in certain subgroups may have affected the results.
One notable limitation of the PHOTON study was the lack of control over the double-masked procedure due to different drug volume vials between groups. While this may raise concerns about bias, the study's blind measurement of visual and anatomical outcomes helped mitigate this issue. Additionally, the use of non-prefilled packaging for aflibercept 8 mg vials raises considerations around the risk of endophthalmitis compared to prefilled syringes, a factor that clinicians will need to weigh against the benefits of extended durability.
In conclusion, the PHOTON study's results suggest that high-dose aflibercept could offer a viable solution to address treatment burden in DMO patients. With promising short-term outcomes indicating extended durability and similar safety profiles to standard dosing, further analysis at 96 weeks will be crucial to confirm these findings and establish the long-term benefits of this treatment approach.
(Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02760-5/fulltext)
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