Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Upadacitinib demonstrated a clear clinical advantage over placebo in the SELECT-AXIS 2 trial, with statistically significant improvements in primary and secondary outcomes, including ASAS40 and BASDAI 50 responses. However, while indirect comparisons suggest similar efficacy to secukinumab and ixekizumab, the credible intervals were wide, indicating some uncertainty.
Cost effectiveness
The cost comparison analysis suggests that upadacitinib has similar costs and overall health benefits as secukinumab and ixekizumab, indicating it is clearly cost-effective under common thresholds, especially considering the commercial arrangement that provides a discount.
Quality of life
The evidence indicates that upadacitinib improves quality of life as measured by the ASQoL, with statistically significant improvements noted. However, the extent of these improvements is moderate and primarily derived from the trial data.
Supporting Domains
Safety and Adverse Effects
The safety profile of upadacitinib is reported to be broadly similar to that of secukinumab and ixekizumab, with manageable adverse events. However, the committee noted that definitive conclusions were difficult due to the nature of the comparisons.
Comparator Selection
Upadacitinib was compared against appropriate comparators (secukinumab and ixekizumab), which are established treatments for the same condition. The committee agreed that these were relevant and suitable comparators for the evaluation.
Patient Population and Subgroups
The trial population of 313 adults with active non-radiographic axial spondyloarthritis is representative of the intended patient population. However, there is limited subgroup analysis reported, which slightly affects the generalizability.
Care Pathway Integration
Upadacitinib’s oral administration offers a convenient alternative to injectable therapies, which may facilitate integration into existing care pathways. Minor adjustments may be needed for its implementation, but overall, it fits well within current practices.
Resource Use and Cost Implications
The budget impact analysis indicates that the costs associated with upadacitinib are similar to or lower than those of secukinumab and ixekizumab, suggesting a manageable budget impact aligned with healthcare planning.
Evidence Quality and Robustness
The evidence is based on a well-conducted randomized controlled trial (SELECT-AXIS 2) and supported by network meta-analyses. However, the committee noted some limitations regarding the heterogeneity of the data and the absence of direct comparisons.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the network meta-analysis and the heterogeneity of the trials, the context of unmet need and the potential benefits of upadacitinib support its use. The overall societal context is favorable.
