Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The evidence from the SELECT-NEXT and SELECT-MONOTHERAPY trials indicates that upadacitinib is more effective than both placebo and methotrexate for treating moderate rheumatoid arthritis. The trials demonstrated statistically significant improvements in ACR20 response rates, with upadacitinib showing a clear clinical advantage over existing treatments. However, the lack of direct head-to-head comparisons with all relevant comparators limits the strength of the evidence.
Cost effectiveness
The cost-effectiveness estimates for upadacitinib with methotrexate fall within NICE’s acceptable range of £20,000 to £30,000 per QALY gained. The committee concluded that the treatment is a reasonable use of Healthcare resources, especially when considering the commercial arrangement that provides a discount.
Quality of life
The company’s mapping algorithms for estimating utility values from HAQ scores are plausible, and both the company and ERG’s approaches were considered acceptable. While the committee noted that the choice of mapping did not significantly affect cost-effectiveness estimates, the evidence suggests moderate improvements in HRQoL for patients treated with upadacitinib.
Supporting Domains
Safety and Adverse Effects
The safety profile of upadacitinib is comparable to that of other biological DMARDs, with the committee concluding that it has an acceptable safety profile. Adverse events were mostly mild to moderate, and serious events were rare, indicating good tolerability.
Comparator Selection
The trials compared upadacitinib against appropriate comparators, including placebo and methotrexate. The committee noted that while conventional DMARDs were used as comparators, the evidence from the SELECT trials was deemed relevant for the moderate rheumatoid arthritis population.
Patient Population and Subgroups
The trials included a diverse population of patients with moderate to severe rheumatoid arthritis, and subgroup analyses were conducted. However, the committee acknowledged that the trials may not fully reflect clinical practice, particularly for patients who cannot tolerate methotrexate.
Care Pathway Integration
Upadacitinib can be integrated into existing treatment pathways with minor adjustments, particularly in patients who have not responded to conventional DMARDs. The committee noted that it fits well within the current clinical practice for moderate rheumatoid arthritis.
Resource Use and Cost Implications
The budget impact of upadacitinib is manageable, especially considering the commercial arrangement that provides a discount. The committee concluded that the resource implications are justifiable given the clinical benefits.
Evidence Quality and Robustness
The evidence base is supported by multiple phase 3 RCTs, although there are some methodological concerns and uncertainties regarding the generalizability of the results. The committee found the evidence to be credible and robust overall.
Uncertainty, Sensitivity, and Broader Impacts
While there are some uncertainties regarding the long-term outcomes and the treatment pathway, the committee found these to be manageable within the context of unmet need for moderate rheumatoid arthritis treatments. The societal context supports the use of upadacitinib.
