Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate

Vera-Llonch, Montserrat; Massarotti, Elena; Wolfe, Frederick; Shadick, Nancy A.; Westhovens, René; Sofrygin, Oleg; Maclean, Ross; Yuan, Ye; Oster, Gerry

doi:10.1093/rheumatology/ken007

Cited by 51 publications

(49 citation statements)

References 27 publications

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“…Pfizer identifies a number of economic evaluations that have assumed either a general risk of mortality associated with RA that is independent of disease severity measures 183,192,194,202,238,284,285 or have expressed mortality as dependent on functional status (typically as expressed by HAQ). 171,180,193,198,231,237,286,287 The Pfizer model adopts the former approach, assuming an age-sex-specific standardised mortality ratio from Brennan et al, 183 who report age-and sex-specific standardised mortality ratios for a UK population.…”

Section: Pfizermentioning

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

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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Section: Pfizermentioning

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

125

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“…None of the studies looked to identify the optimal sequence of treatments from the treatment set included in the analysis. and TNF experienced [75] [66] concluded that rituximab was cost-effective after TNF failure compared to TNF 's. Kielhorn et al (2008) found that rituximab after two TNF failures was cost-effective.…”

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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“…The univariate sensitivity analysis, showed sensitivity of outcomes, mainly to the reduction in the cost / month for the drugs tested. The Abatacept (ABA) has recently been investigated, this results suggested that is costeffective for moderate to severe RA after failure to MTX; based on data from the AIM study (38), resulting in $ 47,910 per QALY gained over 10 years and $ 43,041 to ITH. When failures after one or more anti-TNF are analyzed, Rituximab (RTX) has been profitable (39), this based on data modeling of the REFLEX study.…”

Section: Economic Evaluations Of the Rheumatic Diseasesmentioning

confidence: 99%

Economic Impact of Rheumatic Diseases

Quintana¹,

Coral-Alvarado²

2011

Challenges in Rheumatology

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Cost-effectiveness of abatacept in patients with moderately to severely active rheumatoid arthritis and inadequate response to methotrexate

Abstract: Abatacept is cost-effective by current standards of medical practice in patients with moderately to severely active RA and inadequate response to MTX.

Cited by 51 publications

References 27 publications

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

Economic Impact of Rheumatic Diseases

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