A Test-based Strategy Is More Cost Effective Than Empiric Dose Escalation for Patients With Crohn's Disease Who Lose Responsiveness to Infliximab

doi:10.1016/j.cgh.2012.12.035

Clinical Gastroenterology and Hepatology

Volume 11, Issue 6, June 2013, Pages 654-666

https://doi.org/10.1016/j.cgh.2012.12.035 Get rights and content

Background & Aims

Patients with Crohn's disease who become unresponsive to therapy with tumor necrosis factor antagonists are managed initially with either empiric dose escalation or testing-based strategies. The comparative cost effectiveness of these 2 strategies is unknown. We investigated whether a testing-based strategy is more cost effective than an empiric dose-escalation strategy.

Methods

A decision analytic model that simulated 2 cohorts of patients with Crohn's disease compared outcomes for the 2 strategies over a 1-year time period. The incremental cost-effectiveness ratio of the empiric strategy was expressed as cost per quality-adjusted life-year (QALY) gained, compared with the testing-based strategy. We performed 1-way, probabilistic, and prespecified secondary analyses.

Results

The testing strategy yielded similar QALYs compared with the empiric strategy (0.801 vs 0.800, respectively) but was less expensive ($31,870 vs $37,266, respectively). In sensitivity analyses, the incremental cost-effectiveness ratio of the empiric strategy ranged from $500,000 to more than $5 million per QALY gained. Similar rates of remission (63% vs 66%) and response (28% vs 26%) were achieved through differential use of available interventions. The testing-based strategy resulted in a higher percentage of surgeries (48% vs 34%) and lower percentage use of high-dose biological therapy (41% vs 54%).

Conclusions

A testing-based strategy is a cost-effective alternative to the current strategy of empiric dose escalation for managing patients with Crohn's disease who have lost responsiveness to infliximab. The basis for this difference is lower cost at similar outcomes.

Section snippets

Decision Analysis

The decision analytical model simulated 2 cohorts of Crohn's patients with loss of response to IFX. The model compared the efficacy, costs, and relative cost effectiveness of a testing-based strategy with an empiric dose-escalation strategy. Quality-adjusted life-years (QALYs) and direct costs were calculated based on a 1-year time horizon. The analysis perspective was third-party payer and included treatment and health state costs, but not indirect costs (eg, time missed from work). The model

Comparative Effectiveness and Costs

The testing strategy yielded similar QALYs compared with the empiric strategy (0.801 vs 0.800, respectively) but was less expensive ($31,870 vs $37,266, respectively). Thus, the testing strategy dominated the empiric strategy (numerically higher QALY and lower costs) (Table 2).

Secondary Analyses

At week 52, the proportion of patients in response and remission was similar in both groups (Figure 3A); however, this was achieved differently. Compared with the empiric group, patients in the testing group underwent

Discussion

This decision analysis compared the cost effectiveness of a testing-based algorithm with an empiric algorithm for management of loss of response to IFX. Our results support the hypothesis that a testing-based strategy is a more cost-effective alternative than the currently advocated strategy of empiric dose escalation. The basis for this difference is lower cost at similar outcomes.

To be specific, the lower cost observed for the testing strategy was achieved in 2 ways: (1) less use of high-dose

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A systematic review and a meta-analysis of the literature was conducted to assess efficacy and safety of proactive therapeutic drug monitoring (TDM) versus conventional management during maintenance treatment with anti-tumour necrosis factor (anti-TNFα) in patients with inflammatory bowel disease (IBD).
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Nine studies were identified: one systematic review, six randomised clinical trials, and two cohort studies. No superior efficacy of proactive TDM [relative risk 1.16; 95% confidence interval (CI): 0.98–1.37, n=528; I²=55%] was shown. Proactive TDM could improve the durability of anti-TNFα treatment [odds ratio (OR) 0.12; 95%CI: 0.05–0.27; n=390; I²=45%), prevent acute infusion reactions (OR 0.21; 95%CI: 0.05–0.82; n=390; I²=0%), decrease adverse events (OR 0.38; 95%CI: 0.15–0.98; n=390; I²=14%), and reduce the probability of surgery, at lower economical expenditure.
The analysed evidence did not confirm the superiority of proactive TDM of anti-TNFα treatment over conventional management in patients with IBD, so proactive TDM should not currently be recommended.
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El tratamiento de la enfermedad inflamatoria intestinal (EII) ha sufrido una gran transformación tras la introducción de los fármacos biológicos. Gracias a ellos, los objetivos del tratamiento han evolucionado desde la respuesta y remisión clínica a objetivos más ambiciosos, como la remisión endoscópica o radiológica. Sin embargo, aunque los biológicos son muy eficaces, un porcentaje importante de pacientes no obtendrá una respuesta inicial o la perderá a lo largo del tiempo. Sabemos que existe una relación directa entre las concentraciones valle del biológico y su eficacia terapéutica, que cuanto más exigente sea el objetivo terapéutico serán necesarios niveles superiores del fármaco y que es frecuente la exposición insuficiente al mismo. La monitorización terapéutica de medicamentos biológicos, así como los modelos farmacocinéticos, nos brindan la posibilidad de ofrecer un enfoque personalizado del abordaje en pacientes con EII. Durante los últimos años se ha acumulado información relevante respecto a su utilidad durante o después de la inducción, así como en el mantenimiento del tratamiento biológico, en estrategias reactivas o proactivas y antes de la retirada o desintensificación del esquema.
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The cost of caring for patients with inflammatory bowel disease (IBD) continues to increase worldwide. The cause is not only a steady increase in the prevalence of Crohn's disease and ulcerative colitis in both developed and newly industrialised countries, but also the chronic nature of the diseases, the need for long-term, often expensive treatments, the use of more intensive disease monitoring strategies, and the effect of the diseases on economic productivity. This Commission draws together a wide range of expertise to discuss the current costs of IBD care, the drivers of increasing costs, and how to deliver affordable care for IBD in the future. The key conclusions are that (1) increases in health-care costs must be evaluated against improved disease management and reductions in indirect costs, and (2) that overarching systems for data interoperability, registries, and big data approaches must be established for continuous assessment of effectiveness, costs, and the cost-effectiveness of care. International collaborations should be sought out to evaluate novel models of care (eg, value-based health care, including integrated health care, and participatory health-care models), as well as to improve the education and training of clinicians, patients, and policy makers.
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Citation Excerpt :
The retrospective nature of the historical control group is a clear limitation of this trial. However, after 12 weeks, TDM resulted in a saving of €887 per patient (15%), which is similar to the 14% found by published models of reactive TDM for loss of response to infliximab [33,34]. These studies and their main findings are summarised in Table 1.
Inflammatory bowel disease (IBD) is increasingly common, and results in significant morbidity. Traditional therapies include corticosteroids, aminosalicylates, thiopurines and methotrexate but in more recent years biologics have transformed the management of IBD. However, these agents come with a significant financial cost, making them unavailable for many patients worldwide. Therapeutic drug monitoring (TDM) is an important means to optimise clinical outcomes from pharmacotherapy. Recent studies have also focussed on the cost-effectiveness as an outcome of TDM. TDM of traditional therapies is principally mediated through improved disease control. Cost-savings from TDM of biologic therapies arises mainly from reduced pharmaceutical use with equitable clinical outcomes. This review considers the cost-effectiveness of TDM for IBD therapies, with a focus on recent research into biologic TDM.
A Review of Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Receiving Combination Therapy
2023, Journal of Clinical Medicine

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: Conflicts of interest These authors disclose the following: Fernando Velayos is an advisor for Janssen Pharmaceuticals and UCB Pharma, Inc; and William Sandborn and Brian Feagan are advisors or consultants for Abbott Laboratories, Elan Pharmaceuticals, Janssen Pharmaceuticals, Prometheus Laboratories, and UCB Pharma, Inc. The remaining authors disclose no conflicts.

: Funding Supported by an investigator-initiated research grant from Prometheus Laboratories. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Original articleAlimentary tractA Test-based Strategy Is More Cost Effective Than Empiric Dose Escalation for Patients With Crohn's Disease Who Lose Responsiveness to Infliximab

Background & Aims

Methods

Results

Conclusions

Section snippets

Decision Analysis

Comparative Effectiveness and Costs

Secondary Analyses

Discussion

Clin Gastroenterol Hepatol

Gastroenterology

Gastroenterology

Gastroenterology

Lancet

Gastroenterology

Loss of response and requirement of IFX dose intensification in Crohn's disease: a review

Am J Gastroenterol

Review article: loss of response to anti-TNF treatments in Crohn's disease

Aliment Pharmacol Ther

Influence of immunogenicity on the long-term efficacy of IFX in Crohn's disease

N Engl J Med

Clinical utility of measuring IFX and human anti-chimeric antibody concentrations in patients with inflammatory bowel disease

Am J Gastroenterol

The London position statement of the World Congress of Gastroenterology on biological therapy for IBD with the European Crohn's and Colitis Organization: when to start, when to stop, which drug to choose, and how to predict response?

Am J Gastroenterol

Developing valid and reliable health utilities in irritable bowel syndrome: results from the IBS PROOF cohort

Am J Gastroenterol

Adalimumab induction therapy for Crohn disease previously treated with IFX: a randomized trial

Ann Intern Med

International survey on willingness-to-pay (WTP) for one additional QALY gained: what is the threshold of cost effectiveness?

Health Econ

Certolizumab pegol for the treatment of Crohn's disease

N Engl J Med

IFX, azathioprine, or combination therapy for Crohn's disease

N Engl J Med

Certolizumab pegol for active Crohn's disease: a placebo-controlled, randomized trial

Clin Gastroenterol Hepatol

Doubling the IFX dose versus halving the infusion intervals in Crohn's disease patients with loss of response

Inflamm Bowel Dis

The efficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF antibodies

Aliment Pharmacol Ther

Original article
Alimentary tract
A Test-based Strategy Is More Cost Effective Than Empiric Dose Escalation for Patients With Crohn's Disease Who Lose Responsiveness to Infliximab