Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis

Reveles, Kelly R.; Yang, Min; García-Horton, Viviana; Edwards, Marie Louise; Guo, Amy; Lodise, Thomas P.; Bochan, Markian; Tillotson, Glenn; Dubberke, Erik R.

doi:10.1007/s12325-023-02498-x

Cited by 7 publications

(4 citation statements)

References 46 publications

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“…Recurrence of CDI is common and substantially impacts patient outcomes including increased morbidity and mortality [ 13 – 15 ], compromised HRQL [ 41 – 43 ], and high economic burden [ 44 ]. Because of the high and multifaceted burden imposed by rCDI on patients, there is an increased interest in treating patients at first recurrence to prevent further recurrences, improve their outcomes, and minimize the subsequent health and economic impacts.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection

Feuerstadt,

Allegretti,

Dubberke

et al. 2024

Infect Dis Ther

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Introduction Clostridioides difficile infection (CDI) causes symptoms of varying severity and negatively impacts patients’ health-related quality of life (HRQL). Despite antibiotic treatment, recurrence of CDI (rCDI) is common and imposes clinical and economic burdens on patients. Fecal microbiota, live-jslm (REBYOTA [RBL]) is newly approved in the USA for prevention of rCDI following antibiotic treatments. We analyzed efficacy and HRQL impact of RBL vs. placebo in patients at first rCDI using data from the phase 3 randomized, double-blind placebo-controlled clinical trial, PUNCH CD3. Methods This post hoc analysis included patients at first rCDI fromPUNCH CD3. Treatment success (i.e., absence of diarrhea within 8 weeks post-treatment) was analyzed adjusting for baseline patient characteristics. HRQL was measured using the Clostridioides difficile Quality of Life Survey (Cdiff32); absolute scores and change from baseline in total and domain (physical, mental, and social) scores were summarized and compared between arms. Analyses were conducted for the trial’s blinded phase only. Results Among 86 eligible patients (32.8% of the overall trial population, RBL 53 [61.6%], placebo 33 [38.4%]), RBL-treated patients had significantly lower odds of recurrence (i.e., greater probability of treatment success) at week 8 vs. placebo (odds ratio 0.35 [95% confidence interval 0.13, 0.98]). Probability of treatment success at week 8 was 81% for RBL and 60% for placebo, representing 21% absolute and 35% relative increases for RBL (crude proportions 79.2% vs. 60.6%; relative risk 0.53, p = 0.06). Additionally, RBL was associated with significantly higher Cdiff32 total (change score difference 13.5 [standard deviation 5.7], p < 0.05) and mental domain (16.2 [6.0], p < 0.01) scores vs. placebo from baseline to week 8. Conclusion Compared to placebo, RBL demonstrated a significantly higher treatment success in preventing further rCDI and enhanced HRQL among patients at first recurrence, establishing RBL as an effective treatment to prevent further recurrences in these patients. Trial Registration ClinicalTrials.gov Identifier NCT03244644. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00907-w.

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Section: Discussionmentioning

confidence: 99%

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection

Feuerstadt,

Allegretti,

Dubberke

et al. 2024

Infect Dis Ther

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“… 43 , 44 A recent systematic review and cost synthesis analysis estimated the per-patient per-year rCDI attributable cost is $67,837 to $82,268. 45 Ultimately, CDI recurrence is common and increasingly morbid with each episode in a self-perpetuating cycle. The lack of a standardized easily obtained therapy aimed at breaking this cycle of recurrence by restoring eubiosis to the gut microbiome has long been a missing piece of CDI management.…”

Section: Burden and Morbidity Of Recurrent Clostridioides D...mentioning

confidence: 99%

“… 135 Future financial analysis studies may show the high cost of these products ($17,500 USD for VOWST and $9100 USD for REBYOTA) is worth avoiding a high expenditure hospitalization for rCDI where the direct attributable medical cost can range from $67,837 to $82,268. 45 , 136 Budget impact analysis of potential cost savings for new LBPs is already being published. 137 Similar analyses advocating for bezlotoxumab have been performed and yet pharmacy budgets have not been increased to account for inpatient use and payors continue to impede prescribing it without prior authorization.…”

Section: Clinical Trials Of the Fda Approved Lbps (Rebyota And Vowst)mentioning

confidence: 99%

Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details

Monday,

Tillotson,

Chopra

2024

IDR

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Clostridioides difficile infection (CDI) remains a significant contributor to healthcare costs and morbidity due to high rates of recurrence. Currently, available antibiotic treatment strategies further disrupt the fecal microbiome and do not address the alterations in commensal flora (dysbiosis) that set the stage for CDI. Advances in microbiome-based research have resulted in the development of new agents, classified as live biotherapeutic products (LBPs), for preventing recurrent CDI (rCDI) by restoring eubiosis. Prior to the LBPs, fecal microbiota transplantation (FMT) was available for this purpose; however, lack of large-scale availability and safety concerns have remained barriers to its widespread use. The LBPs are an exciting development, but questions remain. Some are derived directly from human stool while other developmental products contain a defined microbial consortium manufactured ex vivo, and they may be composed of either living bacteria or their spores, making it difficult to compare members of this heterogenous drug class to one another. None have been studied head-to head or against FMT in preventing rCDI. As a class, they have considerable variability in their biologic composition, biopharmaceutic science, route of administration, stages of development, and clinical trial data. This review will start by explaining the role of dysbiosis in CDI, then give the details of the biopharmaceutical components for the LBPs which are approved or in development including how they differ from FMT and from one another. We then discuss the clinical trials of the LBPs currently approved for rCDI and end with the future clinical directions of LBPs beyond C. difficile .

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“…rCDI often results in hospitalization and, in severe cases, can lead to sepsis, colectomy, or even death [10,11]. Moreover, the economic impact of rCDI is substantial, with perpatient per-year rCDI-attributable direct medical costs ranging from USD 67,837 to USD 82,268 in the USA [12]. Against this background, international experts emphasize the urgent need for enhanced strategies to prevent and manage rCDI [13].…”

Section: Introductionmentioning

confidence: 99%

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection

Stallhofer,

Steube,

Katzer

et al. 2024

Visc Med

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Background: Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon. Summary: Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI – antibiotic-induced dysbiosis – hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT. Key Messages: FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.

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Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis

Cited by 7 publications

References 46 publications

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection

Efficacy and Health-Related Quality of Life Impact of Fecal Microbiota, Live-jslm: A Post Hoc Analysis of PUNCH CD3 Patients at First Recurrence of Clostridioides difficile Infection

Microbiota-Based Live Biotherapeutic Products for Clostridioides Difficile Infection- The Devil is in the Details

Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent <i>Clostridioides difficile</i> Infection

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