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Golimumab for the Treatment of Ankylosing Spondylitis: A NICE Single Technology Appraisal

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Abstract

As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the Evidence Review Group (ERG) produced a report to comment on the clinical and cost effectiveness of golimumab (Simponi®, Merck Sharp & Dohme) for the treatment of ankylosing spondylitis (AS) relative to other comparators as presented in the manufacturer’s submission (MS) to NICE. The population was those with active disease who had not responded to conventional therapy. The specified comparators were conventional care and two other tumour necrosis factor alpha (TNF-α) inhibitors (adalimumab and etanercept). Outcomes to be considered were disease activity, functional capacity, disease progression, adverse effects of treatment and health-related quality of life (HR-QOL). There were no head-to-head trials comparing TNF-α inhibitors. The submission included one trial of golimumab versus placebo (the GO-RAISE trial) and additionally seven placebo-controlled randomized controlled trials (RCTs) of other TNF-α inhibitor agents (five with etanercept, and two with adalimumab). The results of these trials were generally a statistically significant improvement from each of the TNF-α inhibitors. A Bayesian mixed treatment comparison (MTC) showed there was generally overlap in the 95 % credible intervals (CrIs) between the TNF-α inhibitors. Exceptions included a greater risk of discontinuation of treatment for golimumab than for etanercept (relative risk [RR] 4.30; 95 % CrI 1.01–18.50). The cost-effectiveness analysis (CEA) compared all of these TNF-α inhibitors. Relative effectiveness was informed only by RR of response (proportion achieving at least a 50 % improvement in Bath AS Disease Activity Index [BASDAI] score; BASDAI50) from the MTC. In the base-case analysis, the incremental cost-effectiveness ratio (ICER) of golimumab versus conventional care was £26,597 and adalimumab and etanercept were extendedly dominated by golimumab. The manufacturer concluded that golimumab is a cost-effective treatment option. Generally, the ERG agreed with the MTC analyses. The main problem was that the MS used data from one trial, which included a period of cross-over. The ERG found some problems with the CEA model, mainly that it did not allow for comparison of TNF-α inhibitor sequences and did not use MTC estimates for treatment discontinuation or adverse events (AEs). The ERG could not correct the sequencing problem, but re-ran the CEA with discontinuations and AEs estimated from the MTC and using the correct trial data. The results of the ERG analysis were that golimumab was extendedly dominated by etanercept, and the preferred treatment was either conventional treatment or etanercept, depending on the ICER threshold. Uncertainty was also substantial. NICE issued guidance (technology appraisal [TA] 233), which recommended golimumab according to the indications described in TA143 for etanercept and adalimumab, i.e. as first-line therapy among the TNF-α inhibitors unless patients are intolerant to one or both alternatives. Given the factors cited by NICE for their decision, the ERG recommends that there should be greater clarity in the NICE methods guidance on handling uncertainty in CEAs as well as the incorporation of benefit from process of care.

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Acknowledgments

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme (project number 08/205/01). See the HTA Programme website for further project information (http://www.hta.ac.uk). This summary of the ERG report was compiled after the Appraisal Committee’s review. The views and opinions expressed are the authors’ and do not necessarily reflect those of NICE or the Department of Health. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author Contributions

Rob Riemsma acted as project lead and systematic reviewer on this appraisal, critiqued the clinical effectiveness methods and evidence, and contributed to the writing of the article. Nigel Armstrong acted as health economist on this assessment, critiqued the manufacturer’s economic evaluation and contributed to the writing of the article. Kate Misso critiqued the search methods in the submission and contributed to the writing of the article. Nathan Manning acted as systematic reviewer, critiqued the clinical effectiveness methods and evidence, and contributed to the writing of the article. Thea van Asselt acted as health economist on this appraisal, critiqued the manufacturer’s economic evaluation and contributed to the writing of the article. Manuela Joore acted as health economic project lead, critiqued the manufacturer’s economic evaluation and contributed to the writing of the article. Florian Tomini acted as health economist on this appraisal, critiqued the manufacturer’s economic evaluation and contributed to the writing of the article. Jos Kleijnen critiqued the manufacturer’s definition of the decision problem and their description of the underlying health problem and current service provision, contributed to the writing of the article and supervised the project. Nigel Armstrong acts as guarantor for the overall content of this article.

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Authors and Affiliations

  1. Kleijnen Systematic Reviews Ltd, Unit 6, Escrick Business Park, Escrick, York, YO19 6FD, UK

    Nigel Armstrong, Kate Misso, Nathan Manning, Jos Kleijnen & Rob Riemsma

  2. Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, The Netherlands

    Manuela Joore, Thea van Asselt & Florian Tomini

  3. School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands

    Jos Kleijnen

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  1. Nigel Armstrong
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Armstrong, N., Joore, M., van Asselt, T. et al. Golimumab for the Treatment of Ankylosing Spondylitis: A NICE Single Technology Appraisal. PharmacoEconomics 31, 415–425 (2013). https://doi.org/10.1007/s40273-013-0049-2

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