Researchers led by clinical experts at the National Institute for Health Research, Moorfields Biomedical Research Centre, London, have reported results from a Healthy Technology Assessment (HTA) evaluating intravitreal ranibizumab (Lucentis), aflibercept (Eylea) and bevacizumab (Avastin) for macular oedema due to central retinal vein occlusion (CRVO). The formal HTA report (Health Technology Assessment Volume: 25, Issue: 38, June 2021) showed that aflibercept was non-inferior to ranibizumab however, the authors suggested that “the possibility that bevacizumab is worse than ranibizumab and aflibercept by 5 visual acuity letters cannot be ruled out”. The significant research work highlighted that “bevacizumab is an economically attractive treatment alternative and would lead to substantial cost savings to the NHS and other health-care systems. However, uncertainty about its relative effectiveness should be discussed comprehensively with patients, their representatives and funders before treatment is considered”.
The comprehensive study was aimed to compare the clinical effectiveness and cost-effectiveness of the three intravitreal anti-VEGF treatments for the management of macula oedema due to central retinal vein occlusion. The trial was set in 44 UK NHS ophthalmology departments including a total of 463 patients and assessing repeated intravitreal injections of ranibizumab (n=155), aflibercept (n=154) or bevacizumab (n=154). The primary outcome used an increase in BCVA up to a duration of 100 weeks and secondary outcomes included questionnaire (VFQ-25), EuroQol-5 Dimensions, side effects and cost-effectiveness measurements (QALY).
Following the adjusted mean changes in the BVCA scores, the results reported ranibizumab, 12.5 letters (standard deviation 21.1 letters); aflibercept, 15.1 letters (standard deviation 18.7 letters); and bevacizumab, 9.8 letters (standard deviation 21.4 letters). This showed that aflibercept was non-inferior to ranibizumab in the intention-to-treat (ITT) population (adjusted mean best corrected visual acuity difference 2.23 letters, 95% confidence interval -2.17 to 6.63 letters; p = 0.0006), but not superior. In addition. the study was unable to demonstrate that bevacizumab was non-inferior to ranibizumab in the ITT population (adjusted mean best corrected visual acuity difference -1.73 letters, 95% confidence interval -6.12 to 2.67 letters; p = 0.071). Finally, a post hoc analysis was unable to demonstrate that bevacizumab was non-inferior to aflibercept in the ITT population (adjusted mean best corrected visual acuity difference was -3.96 letters, 95% confidence interval -8.34 to 0.42 letters; p = 0.32). In terms of the cost-effectiveness, the study showed that bevacizumab was the most cost-effective treatment at a threshold of £20,000-30,000 per quality-adjusted life-year. The detailed report highlighted in its conclusions that, “bevacizumab could be introduced into the NHS as a first-line agent for this condition only after a review of these results and in agreement with patients, their representatives and funders. If patients are fully informed and understand the clinical results of the trial, as our small post-trial patient questionnaire suggests, a majority may consent to bevacizumab treatment with the proviso that licensed medications be available to them as an option if their response to bevacizumab is less than expected. If adopted, bevacizumab would result in substantial savings to the NHS, and potentially to health-care systems around the world”.