Ustekinumab for Treating Moderately to Severely Active Crohn’s Disease after Prior Therapy: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
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As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Janssen to submit evidence on the clinical and cost effectiveness of their drug ustekinumab, an interleukin-12/23 inhibitor, for treating moderate-to-severe active Crohn’s disease (CD). The Centre for Reviews and Dissemination (CRD) and Centre for Health Economics (CHE) Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the Company’s submission, the ERG’s critical review of submitted evidence, and the resulting NICE guidance. The main supporting clinical evidence was derived from four well conducted, randomised controlled trials, comparing ustekinumab with placebo in two sub-populations (conventional care failure and anti-TNFα failure patients) of adults with moderate-to-severe CD. Three trials assessed treatment induction over 8 weeks, while the fourth recruited successfully induced patients into a maintenance trial for 1 year. These trials showed ustekinumab to be more effective than placebo in terms of its ability to induce and maintain clinical response and remission. In the absence of any direct head-to-head data, the Company conducted a network meta-analysis (NMA), which synthesised induction trial data on ustekinumab and relevant comparators (vedolizumab, adalimumab and infliximab) using placebo data as a common comparator. This analysis found ustekinumab to be of comparable efficacy to previously approved biologics in treatment induction. A ‘treatment sequence analysis’ compared long-term treatment efficacy, finding ustekinumab to be comparable in maintaining treatment response and remission to the three other biologic therapies. However, the ERG had identified many limitations and potential bias in this analysis, and urged caution when interpreting the results. The Company’s economic model estimated ustekinumab to be dominant in both sub-populations compared with conventional care; however, the ERG’s preferred base-case estimated an incremental cost-effectiveness ratio of £109,279 in the conventional care failure sub-population, and £110,967 in the anti-TNFα failure sub-population when compared with conventional care. However, the ERG identified significant failings in both the model structure and data inputs, which could not be addressed without complete restructuring. The ERG considered that the economic analysis presented by the Company failed to adequately address the decision problem specified in NICE’s scope. The NICE Appraisal Committee recommended ustekinumab within its market authorisation, on the grounds of sufficiently similar efficacy and costs to previously recommended biologic therapies. However, the ERG’s analyses demonstrated that all currently recommended biologics are unlikely to be cost effective relative to conventional care, raising broader questions regarding the appropriateness of cost-comparison exercises for decision making.
The authors thank Melissa Harden who provided a critical review of the Company’s search strategy and Professor Alan Lobo, Consultant Gastroenterologist and Honorary Professor of Gastroenterology at the University of Sheffield for clinical advice throughout the project.
Robert Hodgson, Mousumi Biswas, Teumzghi Mebrahtu, Matthew Walton, and Nerys Woolacott all formed part of the ERG that produced the ERG report that this paper describes. Robert Hodgson and Matthew Walton wrote the first draft of the manuscript. All authors commented on the manuscript and approved the final version. This summary has not been externally reviewed by PharmacoEconomics.
Compliance with Ethical Standards
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (project number 16/10/12). This summary of the ERG report was compiled after the Appraisal Committee’s review and incorporates additional information and comment from the authors on the STA process and iterations of the NICE guidance not covered by the HTA report. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. This work is Crown copyright (UK).
Conflict of interest
Robert Hodgson, Matthew Walton, Mousumi Biswas, Teumzghi Mebrahtu, and Nerys Woolacott have no conflicts of interest.
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