Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Upadacitinib demonstrated moderate clinical effectiveness compared to placebo, with statistically significant improvements in ACR 20 response and other secondary outcomes. However, it has not been directly compared with other biological DMARDs, leading to some uncertainty in its relative effectiveness.
Cost effectiveness
Upadacitinib is considered cost-effective for patients who have had prior biological DMARDs or for whom TNFi treatments are contraindicated, with ICERs below £20,000 per QALY gained in these populations.
Quality of life
The evidence indicates that psoriatic arthritis significantly impacts health-related quality of life. While upadacitinib is expected to improve HRQoL, the specific data on HRQoL improvements were not robustly detailed in the document.
Supporting Domains
Safety and Adverse Effects
The safety profile of upadacitinib is generally favorable, with mostly mild to moderate adverse events reported. Serious adverse events are rare, indicating a good tolerability compared to existing therapies.
Comparator Selection
While upadacitinib was compared with placebo and adalimumab, the lack of direct comparisons with other biological DMARDs limits the robustness of the evidence regarding its relative effectiveness.
Patient Population and Subgroups
The trial populations included relevant subgroups of patients with psoriatic arthritis, enhancing the generalizability of the findings. However, some limitations in subgroup analyses were noted.
Care Pathway Integration
Upadacitinib can be integrated into existing treatment pathways with minor adjustments, as it is an oral treatment option that does not require significant changes to current practices.
Resource Use and Cost Implications
The economic model indicates a high resource burden for patients who have not previously received a biological DMARD, raising concerns about its affordability in this population.
Evidence Quality and Robustness
The evidence base is supported by pivotal trials, although the reliance on indirect comparisons introduces some uncertainty. Overall, the quality of evidence is acceptable.
Uncertainty, Sensitivity, and Broader Impacts
There are notable uncertainties regarding the indirect comparisons and the economic model, particularly concerning the treatment sequences in clinical practice, which could impact decision-making.
