Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Delgocitinib demonstrated a clear clinical advantage over vehicle cream in the DELTA trials, with significant improvements in IGA-CHE treatment success rates (mean difference of 9.8% and 22.2% in DELTA 1 and DELTA 2, respectively). The evidence suggests that delgocitinib is more effective than alitretinoin based on indirect comparisons, although direct comparisons with phototherapy are lacking.
Cost effectiveness
The cost-effectiveness estimates for delgocitinib are within the acceptable range for NHS resources, with ICERs below the threshold of £20,000 to £30,000 per QALY gained. The committee noted that uncertainties exist, but the overall economic model supports its use.
Quality of life
The utility values derived from the EQ-5D-5L data indicate moderate improvements in health-related quality of life for patients treated with delgocitinib compared to best supportive care. The committee acknowledged that the treatment’s impact on quality of life is significant, although the exact effect sizes were not fully captured.
Supporting Domains
Safety and Adverse Effects
Delgocitinib has a very good safety profile with mostly mild to moderate adverse events reported. The committee noted that the adverse events did not substantially affect the cost-effectiveness results, indicating a favorable tolerability compared to existing treatments.
Comparator Selection
The clinical trials compared delgocitinib against appropriate comparators, including vehicle cream and alitretinoin. Although there was no direct comparison with phototherapy, the indirect comparisons were deemed acceptable by the committee.
Patient Population and Subgroups
The trials included a representative population of adults with moderate to severe chronic hand eczema, and the committee recognized the importance of considering different subgroups, including those with varying disease severity.
Care Pathway Integration
Delgocitinib can be integrated into existing care pathways with minor adjustments. It is positioned as a second-line treatment, which aligns well with current clinical practices for managing chronic hand eczema.
Resource Use and Cost Implications
The budget impact of delgocitinib is manageable, and the committee concluded that it would not impose a significant financial burden on the NHS, especially considering the negotiated discounts.
Evidence Quality and Robustness
The evidence base is supported by multiple phase 3 trials (DELTA 1, DELTA 2, and DELTA FORCE) with low risk of bias. The committee found the overall quality of evidence to be strong, although some uncertainties regarding indirect comparisons remain.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the economic model and treatment effects, the committee noted that these do not significantly undermine the overall conclusions. The treatment addresses a substantial unmet need in chronic hand eczema management.
