Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the KITE and KESTREL trials indicates that brolucizumab is likely to be similarly clinically effective as aflibercept, with both treatments showing comparable outcomes in terms of best corrected visual acuity. However, the committee noted that formal testing of non-inferiority was not possible for subgroup analyses, which introduces some uncertainty. Thus, a moderate benefit is acknowledged.
Cost effectiveness
The cost comparison suggests that brolucizumab has similar costs and overall health benefits to aflibercept and ranibizumab. The committee was satisfied that the total cost of brolucizumab is similar to or lower than the comparators, indicating a clear cost-effective profile under common thresholds.
Quality of life
While the overall rate of adverse events was similar between brolucizumab and aflibercept, concerns regarding intraocular inflammation were raised. This potential adverse effect could negatively impact HRQoL, although the committee concluded that the overall effect on quality-adjusted life years would be small. Therefore, the impact on HRQoL is considered minimal.
Supporting Domains
Safety and Adverse Effects
Brolucizumab has a good benefit-risk profile, with the overall rate of adverse events being similar to aflibercept. Although intraocular inflammation is a concern, it is considered uncommon. The evidence supports that the safety profile is acceptable, thus justifying a rating of A.
Comparator Selection
The committee confirmed that aflibercept and ranibizumab are appropriate comparators as they are both NICE-recommended first-line treatments for diabetic macular oedema. The direct comparison with these established treatments strengthens the evidence base.
Patient Population and Subgroups
The trials included a broad population of adults with diabetic macular oedema, and subgroup analyses were conducted for those with a central subfield thickness of 400 micrometres or more. While there are some limitations, the core population is adequately represented.
Care Pathway Integration
Brolucizumab can be integrated into existing treatment pathways with minor adjustments, as it is an anti-VEGF injection similar to aflibercept and ranibizumab. The committee noted that the treatment fits well within current clinical practice.
Resource Use and Cost Implications
The committee acknowledged that the total cost of brolucizumab is similar to or lower than that of aflibercept and ranibizumab, indicating a manageable budget impact. The economic implications are justifiable given the expected health outcomes.
Evidence Quality and Robustness
The evidence is based on two Phase 3 RCTs (KITE and KESTREL), which provide strong support for the clinical effectiveness of brolucizumab. Although there are some limitations regarding subgroup analyses, the overall evidence quality is robust.
Uncertainty, Sensitivity, and Broader Impacts
There are significant uncertainties regarding the indirect comparisons and subgroup analyses, particularly concerning the effectiveness of brolucizumab compared to ranibizumab. These uncertainties may restrict its use under certain conditions, leading to a B++ rating.
