Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical trial evidence shows that upadacitinib is more effective than placebo for treating moderately to severely active ulcerative colitis, with statistically significant higher remission rates in both induction and maintenance phases. The adjusted treatment differences compared to placebo were 22% and 29% for induction, and 31% and 39% for maintenance, indicating a clear clinical advantage.
Cost effectiveness
The cost-effectiveness estimates for upadacitinib are within the range that NICE typically considers acceptable for Healthcare resources. The committee concluded that it is likely a cost-effective use of resources when conventional or biological treatments are not tolerated or effective enough.
Quality of life
While specific HRQoL data is not extensively detailed, the clinical experts noted that upadacitinib offers additional benefits as an oral treatment that can be taken at home, which likely contributes positively to patients’ quality of life compared to intravenous options. However, the evidence is moderate and lacks extensive validated tools.
Supporting Domains
Safety and Adverse Effects
Upadacitinib has an acceptable safety profile, with common adverse events being mild to moderate. Discontinuation due to adverse events was more common in the placebo group, indicating a favorable tolerability compared to existing treatments.
Comparator Selection
The evidence includes indirect comparisons with other treatments, but there are no direct head-to-head studies. The committee noted that while the indirect treatment comparisons suggest upadacitinib is at least as effective as comparators, the lack of direct evidence limits the robustness of the findings.
Patient Population and Subgroups
The trials included both biologic-naive and biologic-experienced populations, which are relevant to the intended patient population. The committee acknowledged the appropriateness of the subgroup definitions, although they noted potential future reconsideration.
Care Pathway Integration
Upadacitinib can be integrated into existing treatment pathways with minor adjustments, as it is an oral medication that can be taken at home, thus requiring less infrastructure compared to intravenous treatments.
Resource Use and Cost Implications
The economic model indicates that upadacitinib is likely to be a cost-effective option, with manageable budget impacts aligned with Healthcare planning. The committee noted that the treatment’s cost-effectiveness is acceptable given the context of existing treatments.
Evidence Quality and Robustness
The evidence is based on multiple randomized controlled trials with a clear design and low bias risk. However, the reliance on indirect comparisons introduces some limitations, but overall, the evidence is robust.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding the indirect comparisons and the economic model, the committee noted that these are manageable and do not significantly undermine the overall positive assessment of upadacitinib’s value.
