Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence suggests that risankizumab reduces symptoms and increases the likelihood of disease remission compared with placebo. However, the results from indirect comparisons with other biological treatments are uncertain, indicating comparable efficacy to vedolizumab but no clear superiority over TNF-alpha inhibitors or ustekinumab. The committee concluded that while risankizumab is associated with higher rates of clinical remission and endoscopic response compared to placebo, the lack of direct comparative evidence limits the confidence in its effectiveness relative to existing treatments.
Cost effectiveness
Risankizumab is considered cost-saving when compared with vedolizumab in the biological treatment failure population. The committee noted that while it costs more than TNF-alpha inhibitors, it is expected to have at least equivalent clinical effectiveness to vedolizumab, which justifies its cost-effectiveness under certain conditions. The economic models presented support its use as a viable option within the Healthcare.
Quality of life
The evidence indicates that risankizumab can improve quality of life by inducing disease remission, which is crucial for patients with Crohn’s disease. The committee noted that treatments inducing remission are highly valued by patients, as they significantly alleviate debilitating symptoms and improve daily functioning. However, specific HRQoL data from validated instruments were not extensively detailed in the document.
Supporting Domains
Safety and Adverse Effects
Risankizumab has a very good safety profile, with adverse events primarily being mild to moderate. The committee noted that the treatment’s tolerability is comparable to existing therapies, with no significant safety concerns raised in the trials. The evidence supports that serious adverse events are rare, contributing to a favorable assessment of its safety.
Comparator Selection
The committee acknowledged that while risankizumab was compared with appropriate biological treatments, the lack of direct head-to-head trials limits the robustness of the evidence. The indirect comparisons used in the network meta-analyses raised concerns about the validity of the conclusions drawn regarding its comparative effectiveness.
Patient Population and Subgroups
The trials included a diverse patient population with moderately to severely active Crohn’s disease, reflecting the intended real-world use of risankizumab. The committee noted that the evidence was applicable to both conventional care failure and biological treatment failure populations, enhancing the generalizability of the findings.
Care Pathway Integration
Risankizumab can be integrated into existing treatment pathways with minor adjustments. The committee noted that the on-body device for administration is likely to be welcomed by patients, and the company plans to provide training and support for its use, facilitating its adoption in clinical practice.
Resource Use and Cost Implications
The budget impact analysis suggests that risankizumab is manageable within the Healthcare framework, particularly when considering its cost-saving potential compared to vedolizumab. The committee concluded that the resource implications are justifiable given the expected clinical benefits.
Evidence Quality and Robustness
The evidence base is supported by multiple phase 3 trials, although there are some methodological concerns regarding the network meta-analyses. The committee noted that while the trials were well-designed, the reliance on indirect comparisons introduces some uncertainty regarding the robustness of the conclusions.
Uncertainty, Sensitivity, and Broader Impacts
There is notable uncertainty regarding the clinical equivalence of risankizumab compared to TNF-alpha inhibitors and ustekinumab, particularly in the conventional care failure population. The committee highlighted that while the treatment addresses an unmet need, the uncertainties in comparative effectiveness may restrict its use.
