Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Dupilumab demonstrated a clear clinical advantage over placebo in reducing severe asthma exacerbations, with a 47.7% reduction in exacerbation rates and significant improvements in FEV1. However, the evidence is primarily based on a post hoc analysis of a small subgroup, which limits the robustness of the findings.
Cost effectiveness
The updated base-case ICER for dupilumab is £28,156 per QALY gained, which is at the higher end of what NICE considers acceptable. The committee recognized the unmet need and additional benefits that may not be fully captured in the QALY calculation, supporting its cost-effectiveness.
Quality of life
While specific HRQoL data were not extensively detailed, the committee acknowledged that dupilumab could reduce the need for oral corticosteroids, which are associated with significant adverse effects. This suggests a moderate improvement in quality of life for patients with severe asthma.
Supporting Domains
Safety and Adverse Effects
Dupilumab has a very good safety profile, with mostly mild to moderate adverse events reported. The committee noted that it is preferred over oral corticosteroids, which have significant long-term adverse effects, indicating a favorable safety comparison.
Comparator Selection
The comparator for dupilumab was standard care, which is appropriate given the population’s characteristics. The committee concluded that standard care was the right comparator for the updated population, ensuring relevance to clinical practice.
Patient Population and Subgroups
The population included in the clinical trials was broad, but the company’s proposed population for decision-making was narrower and based on a small subgroup. This raises concerns about generalizability and representativeness.
Care Pathway Integration
Dupilumab can be integrated into existing care pathways with minor adjustments, as it is an add-on therapy to standard asthma management. The committee noted that it fits well within current clinical practice.
Resource Use and Cost Implications
The resource implications of dupilumab are manageable, especially considering the potential reduction in the need for oral corticosteroids. The committee acknowledged that the cost implications are justifiable given the benefits.
Evidence Quality and Robustness
While the evidence from the QUEST trial is robust, the reliance on a small post hoc subgroup analysis for the company’s proposed population introduces limitations and uncertainty regarding the overall evidence quality.
Uncertainty, Sensitivity, and Broader Impacts
The committee recognized some uncertainties in the model, particularly regarding mortality estimates and response rates. However, the context of high unmet need and the innovative nature of dupilumab mitigates some of these concerns.
