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Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.

ABSTRACT: Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) remain associated with a reduction in the patients' quality of life and with increased healthcare costs. Bezlotoxumab is a monoclonal antibody against toxin B of C. difficile, approved for prevention of rCDI. In this narrative review, we briefly discuss the pathophysiology of CDI and the mechanism of action of bezlotoxumab, as well as the available evidence from investigational and observational studies in terms of efficacy, effectiveness, and safety of bezlotoxumab for the prevention of rCDI. Overall, bezlotoxumab has proved efficacious in reducing the burden of rCDI, thereby providing clinicians with an important novel strategy to achieve sustained cure. Nonetheless, experiences outside randomized controlled trials (RCTs) remain scant, and mostly represented by case series without a control group. Along with the conduction of RCTs to directly compare bezlotoxumab with faecal microbiota transplantation (or to precisely evaluate the role of their combined use), further widening our post-marketing experience remains paramount to firmly guide the use of bezlotoxumab outside RCTs, and to clearly identify those real-life settings where its preventive benefits can be exploited most.

SUBMITTER: Giacobbe DR

PROVIDER: S-EPMC7452994 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.

Giacobbe Daniele Roberto DR Dettori Silvia S Di Bella Stefano S Vena Antonio A Granata Guido G Luzzati Roberto R Petrosillo Nicola N Bassetti Matteo M

Infectious diseases and therapy 20200706 3

Clostridioides difficile infection (CDI) and recurrent CDI (rCDI) remain associated with a reduction in the patients' quality of life and with increased healthcare costs. Bezlotoxumab is a monoclonal antibody against toxin B of C. difficile, approved for prevention of rCDI. In this narrative review, we briefly discuss the pathophysiology of CDI and the mechanism of action of bezlotoxumab, as well as the available evidence from investigational and observational studies in terms of efficacy, effec ...[more]

PMID: 32632582

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Project description:ObjectivesTreatment 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.MethodsA 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.ResultsFor 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.ConclusionsBased 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.

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:IntroductionPatients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3 years following introduction from a third-party US payer perspective.MethodsA decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3 years were estimated in 2022 US dollars. One-way sensitivity analyses were performed.ResultsFor an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an» average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3 years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022.ConclusionsFMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence.

Dataset Information

Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.

Publications

Bezlotoxumab for Preventing Recurrent Clostridioides difficile Infection: A Narrative Review from Pathophysiology to Clinical Studies.

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