Cost‐effectiveness of biologic response modifiers compared to disease‐modifying antirheumatic drugs for rheumatoid arthritis: A systematic review

Velde, Gabrielle van der; Pham, Ba’; Machado, Márcio; Ieraci, Luciano; Witteman, William; Bombardier, Claire; Krahn, Murray

doi:10.1002/acr.20338

Cited by 74 publications

(49 citation statements)

References 69 publications

(208 reference statements)

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“…The sequential use of TNFis has been a difficult problem to resolve; however, Brennan et al 129 reported favourable incremental cost-effectiveness ratios (ICERs) for using a second TNFi compared with DMARD treatment. A different perspective was taken in a systematic review by van der Velde et al 130 They concluded that the economic evidence suggests that biological treatments are not cost-effective compared with DMARDs for RA in adults at a cost-effectiveness threshold of C$50,000 per QALY and that there is mixed evidence of cost-effectiveness in selected populations at a willingness-to-pay threshold of C$100,000 per QALY.…”

Section: Access To High-cost Treatmentsmentioning

confidence: 99%

Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews

Scott

Ibrahim

Farewell

et al. 2014

Health Technology Assessment

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BackgroundRheumatoid arthritis (RA) is initially treated with methotrexate and other disease-modifying antirheumatic drugs (DMARDs). Active RA patients who fail such treatments can receive tumour necrosis factor inhibitors (TNFis), which are effective but expensive.ObjectiveWe assessed whether or not combination DMARDs (cDMARDs) give equivalent clinical benefits at lower costs in RA patients eligible for TNFis.DesignAn open-label, 12-month, pragmatic, randomised, multicentre, two-arm trial [Tumour necrosis factor inhibitors Against Combination Intensive Therapy (TACIT)] compared these treatment strategies. We then systematically reviewed all comparable published trials.SettingThe TACIT trial involved 24 English rheumatology clinics.ParticipantsActive RA patients eligible for TNFis.InterventionsThe TACIT trial compared cDMARDs with TNFis plus methotrexate or another DMARD; 6-month non-responders received (a) TNFis if in the cDMARD group; and (b) a second TNFi if in the TNFi group.Main outcome measuresThe Heath Assessment Questionnaire (HAQ) was the primary outcome measure. The European Quality of Life-5 Dimensions (EQ-5D), joint damage, Disease Activity Score for 28 Joints (DAS28), withdrawals and adverse effects were secondary outcome measures. Economic evaluation linked costs, HAQ changes and quality-adjusted life-years (QALYs).ResultsIn total, 432 patients were screened; 104 started on cDMARDs and 101 started on TNFis. The initial demographic and disease assessments were similar between the groups. In total, 16 patients were lost to follow-up (nine in the cDMARD group, seven in the TNFi group) and 42 discontinued their intervention but were followed up (23 in the cDMARD group and 19 in the TNFi group). Intention-to-treat analysis with multiple imputation methods used for missing data showed greater 12-month HAQ score reductions with initial cDMARDs than with initial TNFis [adjusted linear regression coefficient 0.15, 95% confidence interval (CI) −0.003 to 0.31;p = 0.046]. Increases in 12-month EQ-5D scores were greater with initial cDMARDs (adjusted linear regression coefficient −0.11, 95% CI −0.18 to −0.03;p = 0.009) whereas 6-month changes in HAQ and EQ-5D scores and 6- and 12-month changes in joint damage were similar between the initial cDMARD group and the initial TNFi group. Longitudinal analyses (adjusted general estimating equations) showed that the DAS28 was lower in the initial TNFi group in the first 6 months (coefficient −0.63, 95% CI −0.93 to −0.34;p < 0.001) but there were no differences between the groups in months 6–12. In total, 36 patients in the initial cDMARD group and 44 in the initial TNFi group achieved DAS28 remission. The onset of remission did not differ between groups (p = 0.085 on log-rank test). In total, 10 patients in the initial cDMARD group and 18 in the initial TNFi group experienced serious adverse events; stopping therapy because of toxicity occurred in 10 and six patients respectively. Economic evaluation showed that the cDMARD group had similar or better QALY outcomes than TNFi with significantly lower costs at 6 and 12 months. In the systematic reviews we identified 32 trials (including 20–1049 patients) on early RA and 19 trials (including 40–982 patients) on established RA that compared (1) cDMARDs with DMARD monotherapy; (2) TNFis/methotrexate with methotrexate monotherapy; and (3) cDMARDs with TNFis/methotrexate. They showed that cDMARDs and TNFis had similar efficacies and toxicities.ConclusionsActive RA patients who have failed methotrexate and another DMARD achieve equivalent clinical benefits at a lower cost from starting cDMARDs or from starting TNFis (reserving TNFis for non-responders). Only a minority of patients achieve sustained remission with cDMARDs or TNFis; new strategies are needed to maximise the frequency of remission.Trial registrationCurrent Control Trials ISRCTN37438295.FundingThis project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full inHealth Technology Assessment; Vol. 18, No. 66. See the NIHR Journals Library website for further project information.

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Section: Access To High-cost Treatmentsmentioning

confidence: 99%

Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews

Scott

Ibrahim

Farewell

et al. 2014

Health Technology Assessment

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“…This has meant that in the last decade the cost of treating RA has progressively increased, above all due to the increased costs of treatment [39]. The findings of the PACTIS study in which patients took only traditional DMARDS [8] are paradigmatic compared to those of the Eco-PR study [13] where 20% of patients were treated with biologics.…”

mentioning

confidence: 99%

“…In the last decade numerous health economics surveys have been published on the use of anti TNF α biologic drugs in RA. Some years ago, an overview and a review of eight pharmacoeconomics studies on anti TNF α drugs [40] and [41] were presented, and very recently a systematic study was published [39] on the cost-effectiveness of biologic drugs in RA in relation to traditional DMARDS, using two willingness-to-pay thresholds to assess cost-effectiveness: Can $50,000 and Can $100,000 per cost per quality-adjusted life year (QALY) gain. At a willingness-to-pay threshold of Can $50,000 per QALY gain the results can be summarised as follows: a) in patients with early RA who have never received methotrexate (MTX), starting with biologic drugs is not cost-effective compared to the use of MTX; b) in patients with RA in whom MTX mono-therapy was not effective, the use of biologics in association with MTX was costeffective compared to continuing with MTX alone; c) in patients in whom MTX combination therapy or sequential DMARDs administration was not effective, the use of biologics was not cost-effective.…”

mentioning

confidence: 99%

“…This can be done through the early treatment of patients who do not respond to traditional DMARDs [39], as well as by identifying the group of patients in whom biologics can be successfully discontinued after a reasonable time without subsequent relapse of disease [11], or by identifying the subjects whose disease activity can be kept low by administering traditional DMARDs alone after the biologics. Indeed, the use of biologics after the MTX failure is cost-effective and there is evidence that these drugs can be successfully discontinued [51] and [52].…”

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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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“…While the clinical position of biologic DMARD in early DMARD-naive patients in terms of effectiveness, safety, and preferences remains an issue for further studies, the above mentioned EULAR overview 3 , as well as a more recent systematic review on cost-effectiveness of biologic DMARD in RA 4 , conclude that it is unlikely that these drugs will be cost-effective as first-line treatment for early RA. Similarly, most national reimbursement schedules do not allow biologics as first-line treatment.…”

mentioning

confidence: 99%

Evaluating Treatment Strategies in Patients with Early Rheumatoid Arthritis: Merging Modeling Theory with Clinical Practice

Boonen¹,

Severens²

2011

J Rheumatol

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Cost‐effectiveness of biologic response modifiers compared to disease‐modifying antirheumatic drugs for rheumatoid arthritis: A systematic review

Cited by 74 publications

References 69 publications

Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews

Randomised controlled trial of Tumour necrosis factor inhibitors Against Combination Intensive Therapy with conventional disease-modifying antirheumatic drugs in established rheumatoid arthritis: the TACIT trial and associated systematic reviews

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

Evaluating Treatment Strategies in Patients with Early Rheumatoid Arthritis: Merging Modeling Theory with Clinical Practice

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