Modelling the cost effectiveness of TNF-  antagonists in the management of rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registry

Brennan, Alan; Bansback, Nick; Nixon, Richard M.; Madan, Jason; Harrison, Mark; Watson, K; Symmons, Deborah

doi:10.1093/rheumatology/kem115

Cited by 112 publications

(92 citation statements)

References 52 publications

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“…Data from Brennan et al 183 were used to estimate the number of hospitalisations within the UK for every cycle of the model dependent on a number of characteristics, including TNF-α inhibitor treatment, which is used as a proxy for bDMARD treatment. The coefficients reported in Brennan et al 183 are reproduced in Table 123.…”

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confidence: 99%

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Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation

Stevenson

Archer

Tosh

et al. 2016

Health Technol Assess

101

125

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ObjectivesRheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX).Data sourcesThe following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs.MethodsNetwork meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained.ResultsSixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX.ConclusionsbDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission).Study registrationThis study is registered as PROSPERO CRD42012003386.FundingThe National Institute for Health Research Health Technology Assessment programme.

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confidence: 99%

“…The coefficients reported in Brennan et al 183 are reproduced in Table 123. Costs of an inpatient day were estimated from NHS reference costs 2010-11 (non-elective inpatient PA34B) with a mean of £517.…”

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confidence: 99%

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation

Stevenson

Archer

Tosh

et al. 2016

Health Technol Assess

101

125

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“…Eight studies (19%) reported significant uncertainty, [39,[45][46][47]49,55,65,73] with six studies (14%) reporting specific model parameters which lead to significant sensitivity in the economic model. These were: the baseline age in the model; [39] the standardised mortality ratios; [39] the algorithm to estimate health related quality of life;, [39,45,65] the rate of disease progression; [45,46] discount rates; [45] treatment response rates; [47] and cost parameters. [49] 6.…”

Section: Health Economic Results In Established Ramentioning

confidence: 99%

Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

2014

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The objective was to assess and critique how sequential disease modifying therapies (DMARDs) have been modelled in the context of economic evaluations of the use of DMARDs for the treatment of Rheumatoid Arthritis (RA). A secondary aim was to identify the methodological challenges of modelling sequential therapies.Systematic searches of 10 databases were undertaken in February 2013. Studies were included if they were English language and reported a full comparative economic evaluation, and they were appraised using the Drummond checklist. Data extracted included economic evaluation data, data relating to sequential treatments, and data on the modelling methods used. 57 studies were identified, with 25 (44%) modelling a sequence of treatments. 43 (75%) were cost-utility analyses. 11 (19%) were UK, and 11 (19%) were US. The remainder were mainly European (26 (46%) studies).There was a distinction between studies in recent-onset RA (14 (25%)), and those in established RA (42 (74%)).One study (1%) was unclear. Individual level models were more likely to meet the Drummond criteria and evaluate sequences. No study identified an optimal sequence of multiple treatments given a set of alternative treatments. The level of reporting about the methods and evidence used to assess the impact of future treatments was generally poor. Where models considered a lifelong time horizon and downstream treatment sequences, evidence gaps were identified.The review identified that methods have not been consistently applied, leading to varied estimates of costeffectiveness. Treatment sequences have not been fully considered and modelled, potentially producing inaccurate estimates of cost-effectiveness.

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“…Contrastingly, for patients on cDMARDs or palliative care the HAQ score was assumed to increase linearly at a rate of 0.045 and 0.06 per year respectively. Changes in EQ-5D were estimated following a linear mapping algorithm from changes in HAQ scores reported by Brennan et al [38]. Mortality was assumed to be affected by HAQ score, with a hazard ratio of 1.43 per HAQ score point applied following Norton et al [39] Unit costs were taken from the Personal Social Services Research Unit,[40] British National Formulary (BNF), [41] and NHS Reference Costs.…”

Section: Cost-effectiveness Evidence Provided By the Companymentioning

confidence: 99%

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

et al. 2017

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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-alpha 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 (i) a comparison against rituximab (RTX) in combination with methotrexate (MTX); (ii) a comparison against bDMARDs when RTX was contraindicated or withdrawn due to an adverse event; and (iii) 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 similar number of QALYs produced at similar, or lower, costs as comparator bDMARDs. The commercial-in-2 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 quality-adjusted life years (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 less 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 to...

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Modelling the cost effectiveness of TNF- antagonists in the management of rheumatoid arthritis: results from the British Society for Rheumatology Biologics Registry

Cited by 112 publications

References 52 publications

Health Economic Modelling of Treatment Sequences for Rheumatoid Arthritis: A Systematic Review

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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