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Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

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Abstract

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (UCB Pharma) of certolizumab pegol (CZP; Cimzia®) to submit evidence of its clinical and cost effectiveness for the treatment of rheumatoid arthritis (RA) following inadequate response to a tumour necrosis factor-α inhibitor (TNFi). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based upon the company’s submission to NICE. The clinical effectiveness evidence in the company’s submission for CZP was based predominantly on six randomised controlled trials (RCTs) comparing the efficacy of CZP against placebo. The clinical effectiveness review identified no head-to-head evidence on the efficacy of CZP against the comparators within the scope; therefore, the company performed a network meta-analysis (NMA). The company’s NMA concluded that CZP had a similar efficacy to that of its comparators. The company submitted a Markov model that assessed the incremental cost effectiveness of CZP versus comparator biologic disease-modifying antirheumatic drugs (bDMARDs) for the treatment of RA from the perspective of the National Health Service for three decision problems, each of which followed an inadequate response to a TNFi. These were (1) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (2) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (3) a comparison against bDMARDs when MTX was contraindicated or withdrawn due to an adverse event. Results from the company’s economic evaluation showed that CZP resulted in a similar number of quality-adjusted life years (QALYs) produced at similar or lower costs compared with comparator bDMARDs. The commercial-in-confidence patient access schemes for abatacept and tocilizumab could not be incorporated by the company, but were incorporated by the ERG in a confidential appendix for the NICE Appraisal Committee (AC). The company estimated that the addition of CZP before RTX in a sequence for patients who could receive MTX produced more QALYs at an increased cost, with a cost per QALY of £33,222. Following a critique of the model, the ERG undertook exploratory analyses that did not change the conclusions reached based on the company’s economic evaluation in relation to the comparison with bDMARDs. The ERG estimated that where CZP replaced RTX, CZP was dominated, as it produced fewer QALYs at an increased cost. The AC concluded that there was little difference in effectiveness between CZP and comparator bDMARDs and that equivalence among bDMARDs could be accepted. The AC consequently recommended CZP plus MTX for people for whom RTX is contraindicated or not tolerated and CZP monotherapy for people for whom MTX is contraindicated or not tolerated. The AC concluded that CZP plus MTX could not be considered a cost-effective use of National Health Service resources when RTX plus MTX is a treatment option.

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Acknowledgements

This summary of the ERG report was compiled after NICE issued the FAD. All authors have commented on the submitted manuscript and have given their approval for the final version to be published. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of NICE or the Department of Health. Any errors are the responsibility of the authors.

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Authors and Affiliations

  1. School of Health and Related Research (ScHARR), University of Sheffield, Regent Court, 30 Regent Street, Sheffield, S1 4DA, UK

    Iñigo Bermejo, Matt Stevenson, Rachel Archer, John W. Stevens, Edward Goka & Mark Clowes

  2. Department of Rheumatology, King’s College Hospital NHS Foundation Trust, London, UK

    David L. Scott

  3. Department of Rheumatology, West Hertfordshire Hospital NHS Trust, Hertfordshire, UK

    Adam Young

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  1. Iñigo Bermejo
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Contributions

IB and MS critiqued the mathematical model provided and the cost-effectiveness analyses submitted by the company. RA and EG critiqued the clinical effectiveness data reported by the company. JWS critiqued the NMA performed by the company. MC critiqued the literature searches undertaken by the company. DLS and AY provided clinical advice to the ERG throughout the project. All authors were involved in drafting and commenting on the final document. IB acts as the guarantor of the manuscript. This summary has not been externally reviewed by PharmacoEconomics.

Corresponding author

Correspondence to Iñigo Bermejo.

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Funding

This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme (Project Number 15/06/07). Visit the HTA programme website for further project information (http://www.hta.ac.uk).

Conflicts of interest

John W. Stevens undertook methodological work for BMS, the manufacturer of abatacept, for ScHARR, although this work was not related to rheumatoid arthritis. The remaining authors have no conflicts of interest to declare.

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Bermejo, I., Stevenson, M., Archer, R. et al. Certolizumab Pegol for Treating Rheumatoid Arthritis Following Inadequate Response to a TNF-α Inhibitor: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics 35, 1141–1151 (2017). https://doi.org/10.1007/s40273-017-0521-5

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