Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a systematic review and economic evaluation

Malottki, K; Barton, Pelham; Tsourapas, A; Uthman, Olalekan A.; Liu, Zulian; Routh, Kristina; Connock, Martin; Jobanputra, Paresh; Moore, David; Fry‐Smith, A; Chen, Yen-Fu

doi:10.3310/hta15140

Cited by 229 publications

(167 citation statements)

References 122 publications

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“…This review differed from other reviews of biologics in RA, 123, [161][162][163][164][165][166][167][168][169][170][171][172] in that it included only licensed doses of biologics, was limited to first-line biologics, and considered separately MTX-naive and cDMARD-experienced trials.…”

Section: Discussion Of Systematic Reviewing Resultsmentioning

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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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: Discussion Of Systematic Reviewing Resultsmentioning

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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“…Of the six TA publications available on the NICE website, [154][155][156][157][158][159] only one contained data for the cost of an AE, namely TA195: Adalimumab, Etanercept, Infliximab, Rituximab and Abatacept for the Treatment of Rheumatoid Arthritis after the Failure of a TNF Inhibitor. 158 A Pfizer CS provided the only relevant cost data in TA195. Pfizer assumed that a SAE involved two general practitioner visits, 7 days of hospitalisation and a utility decrement of 0.05, with a total cost of £1181.…”

Section: Adverse Eventsmentioning

confidence: 99%

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

Shepherd

Cooper²,

Harris³

et al. 2016

Health Technol Assess

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BackgroundJuvenile idiopathic arthritis (JIA) is characterised by joint pain, swelling and a limitation of movement caused by inflammation. Subsequent joint damage can lead to disability and growth restriction. Treatment commonly includes disease-modifying antirheumatic drugs (DMARDs), such as methotrexate. Clinical practice now favours newer drugs termed biologic DMARDs where indicated.ObjectiveTo assess the clinical effectiveness and cost-effectiveness of four biologic DMARDs [etanercept (Enbrel®, Pfizer), abatacept (Orencia®, Bristol-Myers Squibb), adalimumab (Humira®, AbbVie) and tocilizumab (RoActemra®, Roche) – with or without methotrexate where indicated] for the treatment of JIA (systemic or oligoarticular JIA are excluded).Data sourcesElectronic bibliographic databases including MEDLINE, EMBASE, The Cochrane Library and the Database of Abstracts of Reviews of Effects were searched for published studies from inception to May 2015 for English-language articles. Bibliographies of related papers, systematic reviews and company submissions were screened and experts were contacted to identify additional evidence.Review methodsSystematic reviews of clinical effectiveness, health-related quality of life and cost-effectiveness were undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A cost–utility decision-analytic model was developed to compare the estimated cost-effectiveness of biologic DMARDs versus methotrexate. The base-case time horizon was 30 years and the model took a NHS perspective, with costs and benefits discounted at 3.5%.ResultsFour placebo-controlled randomised controlled trials (RCTs) met the inclusion criteria for the clinical effectiveness review (one RCT evaluating each biologic DMARD). Only one RCT included UK participants. Participants had to achieve an American College of Rheumatology Pediatric (ACR Pedi)-30 response to open-label lead-in treatment in order to be randomised. An exploratory adjusted indirect comparison suggests that the four biologic DMARDs are similar, with fewer disease flares and greater proportions of ACR Pedi-50 and -70 responses among participants randomised to continued biologic DMARDs. However, confidence intervals were wide, the number of trials was low and there was clinical heterogeneity between trials. Open-label extensions of the trials showed that, generally, ACR responses remained constant or even increased after the double-blind phase. The proportions of adverse events and serious adverse events were generally similar between the treatment and placebo groups. Four economic evaluations of biologic DMARDs for patients with JIA were identified but all had limitations. Two quality-of-life studies were included, one of which informed the cost–utility model. The incremental cost-effectiveness ratios (ICERs) for adalimumab, etanercept and tocilizumab versus methotrexate were £38,127, £32,526 and £38,656 per quality-adjusted life year (QALY), respectively. The ICER for abatacept versus methotrexate as a second-line biologic was £39,536 per QALY.LimitationsThe model does not incorporate the natural history of JIA in terms of long-term disease progression, as the current evidence is limited. There are no head-to-head trials of biologic DMARDs, and clinical evidence for specific JIA subtypes is limited.ConclusionsBiologic DMARDs are superior to placebo (with methotrexate where permitted) in children with (predominantly) polyarticular course JIA who have had an insufficient response to previous treatment. Randomised comparisons of biologic DMARDs with long-term efficacy and safety follow-up are needed to establish comparative effectiveness. RCTs for JIA subtypes for which evidence is lacking are also required.Study registrationThis study is registered as PROSPERO CRD42015016459.FundingThe National Institute for Health Research Health Technology Assessment programme.

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“…On the other hand, at a willingness-to-pay threshold of Can $100,000 per QALY gain, the results may be outlined thus: 1) the use of biologics in patients who have not previously undergone traditional DMARD treatment is only slightly cost-effective; 2) in patients in whom MTX in mono-therapy was not effective, the use of biologics was cost-effective; 3) in patients who had no response to treatment with MTX in combination with (an)other DMARD(s), introduction of the biologic drug into the treatment programme was costeffective in 14 out of 35 comparisons. As regards other biologic drugs used in the treatment of rheumatoid arthritis, abatacept has been estimated to be cost-effective from the societal perspective in patients who do not respond to MTX and/or to the first TNFα inhibitor [42], [43], [44] and [45]. This is also true for rituximab when it is utilised in patients who fail to respond to the first TNFα, compared to another anti TNFα or a sequence of TNF inhibitors [43], [44], [45] and [46].…”

mentioning

confidence: 99%

“…As regards other biologic drugs used in the treatment of rheumatoid arthritis, abatacept has been estimated to be cost-effective from the societal perspective in patients who do not respond to MTX and/or to the first TNFα inhibitor [42], [43], [44] and [45]. This is also true for rituximab when it is utilised in patients who fail to respond to the first TNFα, compared to another anti TNFα or a sequence of TNF inhibitors [43], [44], [45] and [46]. Rituximab seems to be the most costeffective second line biologic drug [43], [44], [47] and [48].…”

mentioning

confidence: 99%

“…This is also true for rituximab when it is utilised in patients who fail to respond to the first TNFα, compared to another anti TNFα or a sequence of TNF inhibitors [43], [44], [45] and [46]. Rituximab seems to be the most costeffective second line biologic drug [43], [44], [47] and [48]. A recent analysis has demonstrated that the use of tocilizumab is cost-effective if given after the failure of another biological DMARD or as an addition to the current standard of care in the treatment of RA with an inadequate response to DMARDs [49].…”

mentioning

confidence: 99%

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Cost-effectiveness of biologic treatment for rheumatoid arthritis in clinical practice: An achievable target?

Modena

Bianchi²,

Roccatello

2013

Autoimmunity Reviews

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The burden of illness of rheumatoid arthritis (RA) falls on patients, families and society through the direct costs, indirect costs, and intangible costs. A large number of RA cost-of-illness studies have been performed in recent decades with discrepant results due to patient heterogeneity, and different health-care organization, employment rate or social support, job opportunities, and methodologies used to calculate the costs. The greatest burden of RA is the indirect and the intangible costs, but how to estimate them remains controversial. The systematic use of traditional disease modifying anti rheumatic drugs has changed the evolution of the disease. However, a considerable improvement in the management of RA has been obtained since the advent of biologic response modifiers. The use of these drugs, which have demonstrated greater efficacy than conventional therapies, have tripled the direct costs of RA, which rose from about € 4000 to roughly € 12,000, in a period of five years, from 2000 to 2005. The present paper is aimed to examine the effects of this change in therapeutic strategy.

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Adalimumab, etanercept, infliximab, rituximab and abatacept for the treatment of rheumatoid arthritis after the failure of a tumour necrosis factor inhibitor: a systematic review and economic evaluation

Cited by 229 publications

References 122 publications

The clinical effectiveness and cost-effectiveness of abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis: a systematic review and economic evaluation

Cost-effectiveness of biologic treatment for rheumatoid arthritis in clinical practice: An achievable target?

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