The Clinical and Cost Effectiveness of Apremilast for Treating Active Psoriatic Arthritis: A Critique of the Evidence
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As part of the National Institute for Health and Clinical Excellence (NICE) single technology appraisal (STA) process, the manufacturer of apremilast was invited to submit evidence for its clinical and cost effectiveness for the treatment of active psoriatic arthritis (PsA) for whom disease-modifying anti-rheumatic drugs (DMARDs) have been inadequately effective, not tolerated or contraindicated. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This paper provides a description of the ERG review of the company’s submission, the ERG report and submission and summarises the NICE Appraisal Committee’s subsequent guidance (December 2015). In the company’s initial submission, the base-case analysis resulted in an incremental cost-effectiveness ratio (ICER) of £14,683 per quality-adjusted life-year (QALY) gained for the sequence including apremilast (positioned before tumour necrosis factor [TNF]-α inhibitors) versus a comparator sequence without apremilast. However, the ERG considered that the base-case sequence proposed by the company represented a limited set of potentially relevant treatment sequences and positions for apremilast. The company’s base-case results were therefore not a sufficient basis to inform the most efficient use and position of apremilast. The exploratory ERG analyses indicated that apremilast is more effective (i.e. produces higher health gains) when positioned after TNF-α inhibitor therapies. Furthermore, assumptions made regarding a potential beneficial effect of apremilast on long-term Health Assessment Questionnaire (HAQ) progression, which cannot be substantiated, have a very significant impact on results. The NICE Appraisal Committee (AC), when taking into account their preferred assumptions for HAQ progression for patients on treatment with apremilast, placebo response and monitoring costs for apremilast, concluded that the addition of apremilast resulted in cost savings but also a QALY loss. These cost savings were not high enough to compensate for the clinical effectiveness that would be lost. The AC thus decided that apremilast alone or in combination with DMARD therapy is not recommended for treating adults with active PsA that has not responded to prior DMARD therapy, or where such therapy is not tolerated.
KeywordsWell Supportive Care Ustekinumab Evidence Review Group Appraisal Committee Single Technology Appraisal
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 13/169/01). The authors would like to acknowledge Dr Pauline Ho (Consultant Rheumatologist) and Professor Ian Bruce (Lead Clinician), both from the Kellgren Centre for Rheumatology, Central Manchester and Manchester Children’s University Hospitals Trust, for clinical advice throughout the project. Mark Simmonds, Centre for Reviews and Dissemination provided statistical advice. The views and opinions expressed herein are those of 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 summary.
Eleftherios Sideris, Mark Corbett, Stephen Palmer, Laura Bojke and Nerys Woolacott all formed part of the ERG that produced the ERG report that this paper describes. Laura Bojke and Nerys Woolacott took overall responsibility for the cost-effectiveness and clinical effectiveness parts of the project. Eleftherios Sideris wrote the draft of the manuscript. All authors commented on the manuscript and approved the final version.
- 1.National Institute for Health and Care Excellence. https://www.nice.org.uk/guidance/ta368. Accessed 18 Jan 2016.
- 2.Celgene Corporation. Apremilast clinical study report CC-10004-PSA-02. New Jersey: Clegene Corporation; 2013.Google Scholar
- 3.Celgene Corporation. Apremilast clinical study report CC-10004-PSA-003. New Jersey: Celgene Corporation; 2013.Google Scholar
- 4.Celgene Corporation. Apremilast clinical study report CC-10004-PSA-004. New Jersey: Celgene Corporation; 2013.Google Scholar
- 5.NICE quality standards—QS40: Psoriasis. August 2013. National Institute for Health and Care Excellence. http://www.nice.org.uk/guidance/qs40/resources/guidance-psoriasis-pdf. Accessed 1 Mar 2015.
- 6.Biologic drugs commissioning guide—November 2012: Biologic drugs for the treatment of inflammatory disease in rheumatology, dermatology and gastroenterology. National Institute for Health and Care Excellence.Google Scholar
- 7.Population Estimates for UK, England and Wales, Scotland and Northern Ireland, Mid-2013. Data tables. Office for National Statistics. http://www.ons.gov.uk/ons/publications/re-reference-tables.html?edition=tcm%3A77-322718. Accessed 1 Mar 2015.
- 8.CG153. Psoriasis: the assessment and management of psoriasis, October 2012. National Institute for Health and Care Excellence. http://www.nice.org.uk/guidance/cg153/resources/guidance-psoriasis-pdf. Accessed 1 Mar 2015.
- 9.TA199. Etanercept, infliximab and adalimumab for the treatment of psoriatic arthritis, August 2010. National Institute for Health and Care Excellence. https://www.nice.org.uk/guidance/ta199/resources/guidance-etanercept-infliximab-and-adalimumab-for-the-treatment-of-psoriatic-arthritis-pdf. Accessed 1 Mar 2015.
- 10.NICE pathways: Systemic biological therapy for psoriasis and psoriatic arthritis. National Institute for Health and Care Excellence. http://pathways.nice.org.uk/pathways/psoriasis#path=view%3A/pathways/psoriasis/systemic-biological-therapy-for-psoriasis-and-psoriatic-arthritis.xml&content=view-index. Accessed 1 Mar 2015.
- 11.TA220. Golimumab for the treatment of psoriatic arthritis, April 2011. National Institute for Health and Care Excellence. http://www.nice.org.uk/guidance/TA220. Accessed 1 Mar 2015.
- 12.National Institute for Health and Care Excellence. TA 313 Ustekinumab for treating active psoriatic arthritis. London: National Institute for Health and Care Excellence; 2014.Google Scholar
- 13.Wells AF, Edwards CJ, Adebajo AO, Kivitz AJ, Bird P, Shah K, et al. Apremilast in the treatment of DMARD-naive psoriatic arthritis patients: results of a phase 3 randomized, controlled trial (PALACE 4). Arthritis Rheum. 2013;65:3320–1.Google Scholar
- 15.Celgene Corporation. Apremilast clinical study report CC-10004-PSOR-008. New Jersey: Clegene Corporation; 2013.Google Scholar
- 16.Celgene Corporation. Apremilast clinical study report CC-10004-PSOR-009. New Jersey: Celgene Corporation; 2013.Google Scholar
- 18.Hyrich KL, Lunt M, Watson KD, Symmons DP, Silman AJ. Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study. Arthritis Rheum. 2007;56(1):13–20.CrossRefPubMedGoogle Scholar
- 20.Decision Support Unit. Tocilizumab for the treatment of rheumatoid arthritis. Sheffield: Decision Support Unit; 2010.Google Scholar