Dataset Information

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

ABSTRACT:

Objectives

Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin.

Methods

A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effectiveness of standard fidaxomicin, bezlotoxumab plus vancomycin, and extended-pulsed fidaxomicin versus standard oral vancomycin over a lifetime horizon from the US societal perspective.

Results

For overall CDI treatment, oral vancomycin had a cost of $39 178 and was associated with a gain of 11.64 quality-adjusted life-years (QALYs). Extended-pulsed fidaxomicin had a higher QALY gain of 11.65 at a lower cost of $37 613, and therefore was dominant over vancomycin. Standard fidaxomicin had a QALY gain of 11.94 versus vancomycin at an incremental cost of $495 per QALY. Bezlotoxumab plus vancomycin led to a QALY gain of 11.77 at an incremental cost of $17 746 per QALY. At the willingness-to-pay (WTP) threshold of $150 000 per QALY, extended-pulsed fidaxomicin, bezlotoxumab plus vancomycin and standard fidaxomicin were more cost-effective compared with vancomycin alone, yielding incremental net monetary benefits of $3248, $17 011 and $44 308, respectively. One-way sensitivity analysis suggested that the probabilities of sustained cure from the initial episode were the most sensitive inputs, and results were overall not particularly sensitive to any drug costs.

Conclusions

Based on a WTP threshold of $150 000, standard fidaxomicin was estimated to be the most cost-effective treatment. Standard-of-care vancomycin was dominated by extended-pulsed fidaxomicin for treating an episode of CDI and preventing further recurrence, and the addition of bezlotoxumab to vancomycin was dominated by standard fidaxomicin.

SUBMITTER: Chen J

PROVIDER: S-EPMC9478885 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

Chen Jiahe J Gong Cynthia L CL Hitchcock Matthew M MM Holubar Marisa M Deresinski Stanley S Hay Joel W JW

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 20210417 10

<h4>Objectives</h4>Treatment of Clostridioides difficile infection (CDI) has undergone significant change in recent years with the introduction of fidaxomicin and bezlotoxumab. This study evaluated the cost-effectiveness of fidaxomicin and bezlotoxumab for initial CDI compared with standard therapy with oral vancomycin.<h4>Methods</h4>A Markov model with eight health states was built based on transition probabilities, costs and health utilities derived from literature to evaluate the cost-effect ...[more]

PMID: 33878506

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Project description:Clostridioides difficile is the most common cause of infectious antibiotic-associated diarrhea, with disease mediated by two major toxins TcdA and TcdB. In severe cases, systemic disease complications may arise, resulting in fatal disease. Systemic disease in animal models has been described, with thymic damage an observable consequence of severe disease in mice. Using a mouse model of C. difficile infection, we examined this disease phenotype, focussing on the thymus and serum markers of systemic disease. The efficacy of bezlotoxumab, a monoclonal TcdB therapeutic, to prevent toxin mediated systemic disease complications was also examined. C. difficile infection causes toxin-dependent thymic damage and CD4+CD8+ thymocyte depletion in mice. These systemic complications coincide with changes in biochemical markers of liver and kidney function, including increased serum urea and creatinine, and hypoglycemia. Administration of bezlotoxumab during C. difficile infection prevents systemic disease and thymic atrophy, without blocking gut damage, suggesting the leakage of gut contents into circulation may influence systemic disease. As the thymus has such a crucial role in T cell production and immune system development, these findings may have important implications in relapse of C. difficile disease and impaired immunity during C. difficile infection. The prevention of thymic atrophy and reduced systemic response following bezlotoxumab treatment, without altering colonic damage, highlights the importance of systemic disease in C. difficile infection, and provides new insights into the mechanism of action for this therapeutic.Abbreviations: Acute kidney injury (AKI); Alanine Transaminase (ALT); Aspartate Aminotransferase (AST); C. difficile infection (CDI); chronic kidney disease (CKD); combined repetitive oligo-peptides (CROPS); cardiovascular disease (CVD); Double positive (DP); hematoxylin and eosin (H&E); immunohistochemical (IHC); multiple organ dysfunction syndrome (MODS); phosphate buffered saline (PBS); standard error of the mean (SEM); surface layer proteins (SLP); Single positive (SP); wild-type (WT).

Project description:BackgroundNo studies have evaluated the cost-effectiveness of single and two-step different diagnostic test strategies for Clostridioides difficile infection (CDI), including direct and indirect costs.ObjectiveTo evaluate the cost-effectiveness of commonly available diagnostic tests for CDI including nucleic acid amplification testing (NAAT) alone, glutamate dehydrogenase followed by enzyme immunoassay for toxin (GDH/EIA), GDH then NAAT (GDH/NAAT), and NAAT then EIA (NAAT/EIA).DesignDecision tree model from the US societal perspective with inputs derived from the literature. Willingness-to-pay threshold was set at $150,000 per quality-adjusted life year (QALY) gained. To assess the impact of uncertainty in model inputs on the findings, we performed one-way and probabilistic sensitivity analyses.ParticipantsWe conducted the analysis to represent a population aged 65 years old with diarrhea who received a CDI diagnostic test.Main measuresIncremental cost-effectiveness ratios (ICER) and incremental net monetary benefits (INMB).Key resultsNAAT alone was the most cost-effective approach overall; GDH/NAAT was the most cost-effective two-step option. NAAT alone led to the highest QALYs gained, at an incremental cost of $54,547 (vs. GDH/NAAT), $55,410 (vs. GDH/EIA), and $50,231 (vs. NAAT/EIA) per QALY gained. NAAT/EIA was not cost-effective compared to any other strategy. GDH/NAAT resulted in a higher QALY compared to GDH/EIA, at an incremental cost of $96,841 per QALY gained. Variability in the likelihood of comorbidities, CDI probability, and age at disease onset did not substantially change the results. One-way sensitivity analyses showed that results were most sensitive to likelihood of recurrence, followed by CDI mortality rate and probability of severe CDI. Probabilistic sensitivity analyses explored known uncertainties in the base case and confirmed the robustness of the results.ConclusionsNAAT alone and GDH/NAAT (among the two-step options) were the most cost-effective diagnostic test approaches for CDI.

Project description:ImportanceClostridioides difficile infection is the most common hospital-acquired infection in the United States, yet few studies have evaluated the cost-effectiveness of infection control initiatives targeting C difficile.ObjectiveTo compare the cost-effectiveness of 9 C difficile single intervention strategies and 8 multi-intervention bundles.Design, setting, and participantsThis economic evaluation was conducted in a simulated 200-bed tertiary, acute care, adult hospital. The study relied on clinical outcomes from a published agent-based simulation model of C difficile transmission. The model included 4 agent types (ie, patients, nurses, physicians, and visitors). Cost and utility estimates were derived from the literature.InterventionsDaily sporicidal cleaning, terminal sporicidal cleaning, health care worker hand hygiene, patient hand hygiene, visitor hand hygiene, health care worker contact precautions, visitor contact precautions, C difficile screening at admission, and reduced intrahospital patient transfers.Main outcomes and measuresCost-effectiveness was evaluated from the hospital perspective and defined by 2 measures: cost per hospital-onset C difficile infection averted and cost per quality-adjusted life-year (QALY).ResultsIn this agent-based model of a simulated 200-bed tertiary, acute care, adult hospital, 5 of 9 single intervention strategies were dominant, reducing cost, increasing QALYs, and averting hospital-onset C difficile infection compared with baseline standard hospital practices. They were daily cleaning (most cost-effective, saving $358 268 and 36.8 QALYs annually), health care worker hand hygiene, patient hand hygiene, terminal cleaning, and reducing intrahospital patient transfers. Screening at admission cost $1283/QALY, while health care worker contact precautions and visitor hand hygiene interventions cost $123 264/QALY and $5 730 987/QALY, respectively. Visitor contact precautions was dominated, with increased cost and decreased QALYs. Adding screening, health care worker hand hygiene, and patient hand hygiene sequentially to the daily cleaning intervention formed 2-pronged, 3-pronged, and 4-pronged multi-intervention bundles that cost an additional $29 616/QALY, $50 196/QALY, and $146 792/QALY, respectively.Conclusions and relevanceThe findings of this study suggest that institutions should seek to streamline their infection control initiatives and prioritize a smaller number of highly cost-effective interventions. Daily sporicidal cleaning was among several cost-saving strategies that could be prioritized over minimally effective, costly strategies, such as visitor contact precautions.

Dataset Information

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

Objectives

Methods

Results

Conclusions

Publications

Cost-effectiveness of bezlotoxumab and fidaxomicin for initial Clostridioides difficile infection.

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