Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for anakinra after conventional DMARDs is limited, with small patient numbers in trials leading to high uncertainty. The committee concluded that it is reasonable to assume that anakinra is as effective as tocilizumab, but the lack of direct comparative evidence and the small sample sizes undermine the strength of the clinical effectiveness claims.
Cost effectiveness
Cost-effectiveness estimates for anakinra are uncertain due to issues with the economic model and the lack of robust clinical evidence. The committee concluded that a cost-minimisation analysis was sufficient, indicating similar costs to tocilizumab, but the overall economic value remains questionable.
Quality of life
The committee acknowledged that Still’s disease significantly affects health-related quality of life, with patient experts describing substantial impacts on daily living and personal relationships. The potential for anakinra to improve disease control and quality of life is recognized, although specific HRQoL data from trials are limited.
Supporting Domains
Safety and Adverse Effects
The safety profile of anakinra is considered very good, with adverse events being mostly mild or moderate. The committee noted that both anakinra and tocilizumab have similar adverse event profiles, which supports the conclusion of acceptable safety.
Comparator Selection
The committee recognized that while tocilizumab is a relevant comparator, the lack of direct trial evidence comparing anakinra with it limits the robustness of the evidence. The committee concluded that canakinumab is not a relevant comparator, which further complicates the evidence landscape.
Patient Population and Subgroups
The patient population for anakinra includes both adults and children with Still’s disease, which is a rare condition. The committee noted that the trials included patients who had previously failed conventional DMARDs, aligning with the intended use of the drug.
Care Pathway Integration
Anakinra can be integrated into existing treatment pathways for Still’s disease, although the committee noted that current Healthcare policies may delay its use. The potential for earlier access to biological DMARDs is recognized as beneficial for patient outcomes.
Resource Use and Cost Implications
The economic model presented by the company was deemed unsuitable for decision-making, raising concerns about the resource burden associated with anakinra. The committee acknowledged that while the cost-minimisation analysis suggests similar costs to tocilizumab, the overall resource implications remain uncertain.
Evidence Quality and Robustness
The evidence base for anakinra is limited, with small sample sizes and methodological concerns in the trials. The committee noted significant uncertainties in the clinical data, which affects the overall robustness of the evidence.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the clinical effectiveness and cost-effectiveness of anakinra, which may restrict its use. The committee acknowledged the potential for improved outcomes if used earlier in the treatment pathway, but the lack of robust evidence limits confidence in this approach.
