Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
Upadacitinib has shown moderate clinical effectiveness in treating active ankylosing spondylitis, demonstrating statistically significant improvements compared to placebo in primary and secondary outcomes across two randomized controlled trials. However, while indirect comparisons with secukinumab and ixekizumab suggest similar effectiveness, the evidence lacks robust long-term data, leading to a moderate rating.
Cost effectiveness
The cost comparison analysis suggests that upadacitinib has similar costs and overall health benefits compared to secukinumab and ixekizumab. The committee concluded that the total costs associated with upadacitinib were similar to or lower than those of the comparators, supporting its cost-effectiveness.
Quality of life
The evidence indicates that upadacitinib leads to improvements in quality of life, as measured by the Ankylosing Spondylitis Quality of Life (ASQoL) measure. However, the improvements are moderate and primarily derived from specific trial populations, which limits the generalizability of these findings.
Supporting Domains
Safety and Adverse Effects
Upadacitinib has a good safety profile with mostly mild to moderate adverse events reported. The clinical expert indicated that the adverse event profile is unlikely to differ significantly from that of secukinumab, suggesting a favorable safety profile.
Comparator Selection
The appraisal committee considered secukinumab and ixekizumab as appropriate comparators for upadacitinib, aligning with NICE’s previous recommendations. The choice of comparators is relevant and reflects current clinical practice, enhancing the validity of the evidence.
Patient Population and Subgroups
The trial populations for upadacitinib included both biological-naive and biological-experienced patients, which reflects the intended real-world patient population. However, there are some limitations in subgroup analyses, particularly regarding long-term efficacy data.
Care Pathway Integration
Upadacitinib can be integrated into existing care pathways with minor adjustments, as it is recommended for patients who have not responded adequately to conventional therapy. The treatment aligns well with current clinical practices for ankylosing spondylitis.
Resource Use and Cost Implications
The overall resource implications of adopting upadacitinib are manageable, with the cost comparison indicating that it does not impose a significant burden on the healthcare system. The committee noted that the total costs are similar to those of existing treatments.
Evidence Quality and Robustness
The evidence base includes randomized controlled trials and network meta-analyses, which provide a strong foundation for the appraisal. However, there are some uncertainties regarding long-term efficacy and adherence, which slightly detract from the robustness of the evidence.
Uncertainty, Sensitivity, and Broader Impacts
While there are uncertainties regarding long-term efficacy and potential additional monitoring costs, the overall context is favorable, with the treatment addressing a significant unmet need in ankylosing spondylitis management.
