Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence shows that dupilumab improves symptoms of prurigo nodularis compared with best supportive care. However, the trials excluded many treatments typically used in the Healthcare, leading to uncertainty about the generalizability of the results. The committee noted that the effectiveness of dupilumab is likely reduced for people who weigh over 90 kg, which adds to the uncertainty.
Cost effectiveness
The cost-effectiveness estimates for dupilumab were found to be above the acceptable range for Healthcare resources, with the EAG’s preferred base-case ICER being £37,300 per QALY gained. The committee expressed concerns about the uncertainty in the economic model, which further complicates the cost-effectiveness assessment.
Quality of life
The trials included quality-of-life data, and the results indicated a statistically significant improvement in quality of life for patients receiving dupilumab compared to best supportive care. However, the overall impact on HRQoL was not fully explored in the context of the Healthcare standard care, which limits the robustness of this finding.
Supporting Domains
Safety and Adverse Effects
Dupilumab was reported to have a very good safety profile with mostly mild or moderate adverse events. Serious adverse events were rare, indicating that the treatment is generally well-tolerated compared to existing therapies.
Comparator Selection
The company excluded several relevant comparators from its submission, including antihistamines, oral corticosteroids, and immunosuppressants, which are commonly used in the Healthcare. This exclusion raises concerns about the validity of the comparison made in the trials.
Patient Population and Subgroups
The trial populations were not fully representative of the Healthcare population, particularly regarding age and weight. The committee noted that the average age of the trial population was around 10 years younger than the typical Healthcare population, which may affect the treatment’s effectiveness.
Care Pathway Integration
Dupilumab is positioned as an alternative for later treatments in the stepped approach to managing prurigo nodularis, indicating that it can be integrated into existing care pathways with minor adjustments.
Resource Use and Cost Implications
The economic model indicated a notable cost burden, with the committee expressing concerns about the high ICER estimates. The potential additional costs for non-responders were also deemed inappropriate, which raises concerns about the overall resource implications.
Evidence Quality and Robustness
While the evidence from the phase 3 trials is robust, there are significant concerns regarding the generalizability of the results due to the exclusion of relevant treatments from the best supportive care. This limits the overall robustness of the evidence.
Uncertainty, Sensitivity, and Broader Impacts
There are high levels of uncertainty surrounding the clinical and economic evidence, particularly due to the exclusion of relevant comparators and the assumptions made in the economic model. This uncertainty may restrict the use of dupilumab in practice.
