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Ocrelizumab for Treating Patients with Primary Progressive Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal


Ocrelizumab is indicated for relapsing remitting and primary progressive multiple sclerosis (RRMS and PPMS, respectively). In an appraisal undertaken by the National Institute for Health and Care Excellence (NICE), the company Roche presented the evidence for ocrelizumab used in patients with PPMS, which came from one single randomised controlled trial (RCT) comparing ocrelizumab versus placebo. Based on results from this trial, the licensed indication was restricted to patients with early PPMS in terms of disease duration and level of disability, and with imaging features characteristic of inflammatory activity. Overall, the Evidence Review Group (ERG) found that the RCT had a low risk of bias. In the post-hoc defined magnetic resonance imaging (MRI) active subgroup, matching the label indication, the risk of confirmed disability progression sustained for 12 weeks (CDP-12) was significantly delayed in the ocrelizumab group compared to placebo. However, considering the same risk with progression sustained for 24 weeks (CDP-24), which was deemed the most clinically relevant, the benefit from ocrelizumab did not reach statistical significance. In the same MRI active subgroup, benefits from ocrelizumab on functional outcomes and on health-related quality of life were not clearly demonstrated. A de novo Markov model was used to estimate the cost-effectiveness of ocrelizumab versus best supportive care (BSC) for treating patients with PPMS. Health states were defined by the Expanded Disability Status Scale (EDSS), ranging from 0 to 9. Disability progression was based on the MSBase natural history cohort that exhibited disease progression in the absence of disease-modifying therapy. Treatment with ocrelizumab delayed disability progression, with evidence of its clinical effectiveness obtained from the RCT. The economic analysis was undertaken from the National Health Service and Personal Social Services perspective, and the outcomes were reported in terms of life years gained and quality-adjusted life years (QALYs), with the overall results reported in terms of an incremental cost-effectiveness ratio (ICER), expressed as cost per QALY gained over a 50-year time horizon. Both costs and effects were discounted at 3.5% per annum. The company undertook deterministic one-way sensitivity analyses and scenario analyses, including probabilistic sensitivity analysis (PSA). The ERG raised several concerns, which were discussed at the appraisal committee meetings, resulting in the committee’s preferences being applied and a revised economic analysis from the company. Under an approved patient access scheme with appraisal committee preferences applied, analyses yielded an ICER of approximately £78,300 per QALY. Sensitivity analysis results indicated that the treatment effect on CDP-12 had the greatest impact. Results for the PSA showed that at a willingness-to-pay threshold of £30,000 per QALY gained, ocrelizumab versus BSC had a zero probability of being cost-effective. Following new analyses submitted by the company, with a revised confidential patient access scheme, NICE recommended ocrelizumab in the treatment of early PPMS in adults with imaging features characteristic of inflammatory activity.

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  1. National Institute for Health and Care Excellence. Guide to the methods of technology appraisal 2013. 2013. Accessed 20 Mar 2018.

  2. Thompson AJ, Baranzini SE, Geurts J, Hemmer B, Ciccarelli O. Multiple sclerosis. Lancet. 2018;391(10130):1622–36.

    Article  Google Scholar 

  3. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sorensen PS, Thompson AJ, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–86.

    Article  Google Scholar 

  4. Miller DH, Leary SM. Primary-progressive multiple sclerosis. Lancet Neurol. 2007;6(10):903–12.

    Article  Google Scholar 

  5. National Institute for Health and Care Excellence. Lower price for MS drugs paves the way for positive recommendation from NICE. 2019. Accessed 25 Sep 2019.

  6. National Clinical Guideline Centre. Multiple sclerosis: management of multiple sclerosis in primary and secondary care. Clinical guideline 186. 2014. Accessed 10 Apr 2018.

  7. European Medicines Agency (EMA). European Public Assessment Report: Ocrevus. 2017. Accessed 19 Mar 2018.

  8. National Institute for Health and Care Excellence. Ocrelizumab for treating relapsing–remitting multiple sclerosis: technology appraisal guidance [TA533]. 2018. Accessed 29 Aug 2019.

  9. Hawker K, O’Connor P, Freedman MS, Calabresi PA, Antel J, Simon J, et al. Rituximab in patients with primary progressive multiple sclerosis: results of a randomized double-blind placebo-controlled multicenter trial. Ann Neurol. 2009;66(4):460–71.

    Article  CAS  Google Scholar 

  10. Montalban X, Hauser SL, Kappos L, Arnold DL, Bar-Or A, Comi G, et al. Ocrelizumab versus placebo in primary progressive multiple sclerosis. N Engl J Med. 2017;376(3):209–20.

    Article  CAS  Google Scholar 

  11. Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10023):1075–84.

    Article  CAS  Google Scholar 

  12. Feys P, Lamers I, Francis G, Benedict R, Phillips G, LaRocca N, et al. The Nine-Hole Peg Test as a manual dexterity performance measure for multiple sclerosis. Mult Scler. 2017;23(5):711–20.

    Article  Google Scholar 

  13. Institute for Clinical and Economic Review. Disease-modifying therapies for relapsing remitting and primary-progressive multiple sclerosis: effectiveness and value. 2017. Accessed 19 Apr 2018.

  14. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444–52.

    Article  CAS  Google Scholar 

  15. Butzkueven H, Chapman J, Cristiano E, Grand’Maison F, Hoffmann M, Izquierdo G, et al. MSBase: an international, online registry and platform for collaborative outcomes research in multiple sclerosis. Mult Scler. 2006;12(6):769–74.

    Article  CAS  Google Scholar 

  16. Orme M, Kerrigan J, Tyas D, Russell N, Nixon R. The effect of disease, functional status, and relapses on the utility of people with multiple sclerosis in the UK. Value Health. 2007;10(1):54–60.

    Article  Google Scholar 

  17. National Institute for Health and Care Excellence. Natalizumab for the treatment of adults with highly active relapsing–remitting multiple sclerosis. 2007. Accessed 22 Mar 2018.

  18. Tyas D, Kerrigan J, Russell N, Nixon R. The distribution of the cost of multiple sclerosis in the UK: how do costs vary by illness severity? Value Health. 2007;10(5):386–9.

    Article  Google Scholar 

  19. Focosi D, Tuccori M, Maggi F. Progressive multifocal leukoencephalopathy and anti-CD20 monoclonal antibodies: what do we know after 20 years of rituximab. Rev Med Virol. 2019;1:e2077.

    Google Scholar 

  20. National Institute for Health and Care Excellence. Final appraisal document: ocrelizumab for treating primary progressive multiple sclerosis. 2019. Accessed 3 Jan 2020.

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The views expressed in this report are those of the authors and not necessarily those of the NHS, the National Institute for Health Research (NIHR), NIHR Evaluation, Trials and Studies Coordinating Centre (NETSCC), the HTA programme, or the Department of Health. Any errors are the responsibility of the authors. This report is supported by OC, who is a researcher at the NIHR University College London Hospitals (UCLH) Biomedical Research Centre.

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PA, JC, MC, EL, RC, OC, CC, and XA were authors of the ERG report on which this paper is based. PA and XA produced the first draft of the manuscript. All authors commented on the manuscript and approved the final version. This article has not been externally peer reviewed by PharmacoEconomics.

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Correspondence to Peter Auguste.

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This project was funded by the NIHR HTA programme (project number 16/56/22). See the HTA programme website ( for further project information:

Conflict of interest

PA, JC, MC, EL, RC, CC, and XA have no conflicts of interest that are directly relevant to the content of this article. OC is an NIHR Research Professor and has received grants from the UK MS Society, National MS Society, NIHR-HTA, and Rosetrees Trust, and has served as a consultant for Roche, Merck, Teva, Novartis, and Biogen. She is an Associate Editor of Neurology, for which she receives an honorarium.

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Auguste, P., Colquitt, J., Connock, M. et al. Ocrelizumab for Treating Patients with Primary Progressive Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal. PharmacoEconomics 38, 527–536 (2020).

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