Upadacitinib for treating active non-radiographic axial spondyloarthritis

3.1 The company proposed that upadacitinib should be considered in adults as an alternative to the currently NICE-recommended interleukin (IL)‑17 inhibitors secukinumab and ixekizumab for active non-radiographic axial spondyloarthritis that is not controlled well enough with conventional therapy and when TNF‑alpha inhibitors are not suitable or do not control the condition well enough. The committee agreed that the proposed population was consistent with previous recommendations for IL‑17 inhibitors for active non-radiographic axial spondyloarthritis, and with their use in clinical practice. The company presented a comparison with 2 NICE-recommended IL‑17 inhibitors (NICE technology appraisal guidance on secukinumab for treating non-radiographic axial spondyloarthritis and ixekizumab for treating axial spondyloarthritis). The committee agreed that this was consistent with the criteria for a cost-comparison evaluation.

3.2 Secukinumab and ixekizumab are anti‑IL-17 injections recommended by NICE for treating non-radiographic axial spondyloarthritis. Upadacitinib is an oral JAK inhibitor. The clinical and patient experts highlighted the convenience of upadacitinib over IL‑17 inhibitors owing to its oral administration. They also suggested that upadacitinib would be especially helpful for people with needle phobias or dexterity issues that make self-injecting difficult. Clinical advice to the EAG suggested that secukinumab is chosen more often than ixekizumab for treating active non-radiographic axial spondyloarthritis. Secukinumab has been available for ankylosing spondylitis since 2016, suggesting that secukinumab is more established in NHS clinical practice than ixekizumab, which became available in 2021. The committee concluded that secukinumab and ixekizumab are appropriate comparators for upadacitinib, but that secukinumab was the more relevant comparator.

3.3 Upadacitinib has been studied in 1 randomised controlled trial including 313 adults with active non-radiographic axial spondyloarthritis (SELECT‑AXIS 2, study 2). It was compared with placebo. In SELECT‑AXIS 2, study 2, upadacitinib was associated with statistically significant improvements compared with placebo in the primary and secondary outcomes, including the Assessment in Spondyloarthritis international Society 40% (ASAS40) response, BASDAI 50 score and total back pain score. Upadacitinib was associated with higher ASAS40 and BASDAI 50 responses and total back pain score improvement at week 14 than placebo. People having upadacitinib also had statistically significantly higher scores in the Ankylosing Spondylitis Quality of Life (ASQoL) measure. The committee concluded that upadacitinib was more clinically effective than placebo.

3.4 The company did a series of network meta-analyses comparing clinical-effectiveness data for upadacitinib (SELECT‑AXIS 2, study 2) with data for secukinumab (PREVENT) and ixekizumab (COAST‑X). The analyses investigated measures of efficacy, including binary outcomes (ASAS40, BASDAI 50) and continuous outcomes (BASDAI [change from baseline] and Bath Ankylosing Spondylitis Functional Index [change from baseline]). The EAG highlighted that although the median values favoured upadacitinib over ixekizumab (except for BASDAI 50 score) and secukinumab, the credible intervals were wide. It explained that the health benefits for all treatments could be similar, but could also differ. The clinical experts stated in their submission that they would expect upadacitinib to provide clinically meaningful benefits compared with IL‑17 inhibitors. The EAG also identified heterogeneity between the trials included in the network meta-analysis that may impact its validity, but acknowledged that there were no studies available that directly compared upadacitinib with either secukinumab or ixekizumab. The committee confirmed this and noted that uncertainties relating to heterogeneity were unlikely to be resolved by a more detailed cost–utility analysis. The committee concluded that the network meta-analysis was uncertain, but supported the company's position that upadacitinib has similar clinical effectiveness to secukinumab and ixekizumab.

3.5 The company provided safety data comparing upadacitinib with placebo (SELECT‑AXIS 2, study 2), secukinumab (PREVENT) and ixekizumab (COAST‑X). The company and EAG agreed that the safety profiles of all treatments were broadly similar. However, the EAG highlighted that the company had only provided naive comparisons, and the differences between adverse event incidence between the trials was likely to be influenced by differences in trial design, length of follow up and differences in adverse event definitions in each trial. The committee agreed with the EAG. It concluded that it was difficult to draw definitive conclusions from the safety data, and formal modelling of the available safety data would have been helpful for decision making.

3.6 The company presented a base-case cost-comparison analysis that modelled the total costs of upadacitinib, secukinumab and ixekizumab over 5 years. It also provided a scenario analysis modelling the costs over 10 years. It considered that the clinical evidence available supported the assumption of clinical equivalence between upadacitinib, secukinumab and ixekizumab. The EAG was satisfied with the company's cost-comparison analysis methods, so did not provide its own cost-comparison estimates. Taking into account the confidential patient access schemes for upadacitinib, secukinumab and ixekizumab, the committee concluded that the total costs associated with upadacitinib were similar to or lower than those associated with secukinumab and ixekizumab. The discounts for all treatments are confidential, so the incremental costs cannot be shared here.

3.7 The committee concluded that the criteria for a cost comparison were met because: