Bezlotoxumab for Clostridium difficile Infection Complicating Inflammatory Bowel Disease

Kelly, Ciarán P.; Wilcox, Mark H.; Glerup, Henning; Aboo, Nazimuddin; Ellison, Misoo C.; Eves, Karen; Dorr, Mary Beth

doi:10.1053/j.gastro.2018.06.080

Cited by 15 publications

(11 citation statements)

References 7 publications

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“… 35 A post hoc analysis in the IBD sub-population from phase III clinical trials showed a trend of reduction in recurrent CDI in the bezlotoxumab group compared with placebo [27.2% absolute reduction with 95% confidence interval (CI) of −57.9 to 9.6]. 36 …”

Section: Treatmentmentioning

confidence: 99%

The interplay of Clostridioides difficile infection and inflammatory bowel disease

Sehgal

Yadav

Khanna

2021

Therap Adv Gastroenterol

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Inflammatory bowel disease (IBD) is a chronic disease of the intestinal tract that commonly presents with diarrhea. Clostridioides difficile infection (CDI) is one of the most common complications associated with IBD that lead to flare-ups of underlying IBD. The pathophysiology of CDI includes perturbations of the gut microbiota, which makes IBD a risk factor due to the gut microbial alterations that occur in IBD, predisposing patients CDI even in the absence of antibiotics. Superimposed CDI not only worsens IBD symptoms but also leads to adverse outcomes, including treatment failure and an increased risk of hospitalization, surgery, and mortality. Due to the overlapping symptoms and concerns with false-positive molecular tests for CDI, diagnosing CDI in patients with IBD remains a clinical challenge. It is crucial to have a high index of suspicion for CDI in patients who seem to be experiencing an exacerbation of IBD symptoms. Vancomycin and fidaxomicin are the first-line treatments for the management of CDI in IBD. Microbiota restoration therapies effectively prevent recurrent CDI in IBD patients. Immunosuppression for IBD in IBD patients with CDI should be managed individually, based on a thorough clinical assessment and after weighing the pros and cons of escalation of therapy. This review summarizes the epidemiology, pathophysiology, the diagnosis of CDI in IBD, and outlines the principles of management of both CDI and IBD in IBD patients with CDI.

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Section: Treatmentmentioning

confidence: 99%

The interplay of Clostridioides difficile infection and inflammatory bowel disease

Sehgal

Yadav

Khanna

2021

Therap Adv Gastroenterol

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“…52 Post-hoc analysis from 2 large clinical trials, demonstrated that bezlotoxumab was safe and was associated with a trend for a 50% relative reduction in the incidence of recurrent CDI. 53 Therefore, bezlotoxumab can be considered as a recurrence prevention strategy in IBD patients with CDI.…”

Section: Recurrence Prevention Strategiesmentioning

confidence: 99%

“…Bezlotoxumab (now an approved therapy by the U.S. FDA) is a monoclonal antibody against the C. difficile toxin B, which has shown to prevent recurrent CDI; while given as a one-time intravenous infusion during antibiotic treatment for CDI [ 52 ]. Post-hoc analysis from 2 large clinical trials, demonstrated that bezlotoxumab was safe and was associated with a trend for a 50% relative reduction in the incidence of recurrent CDI [ 53 ]. Therefore, bezlotoxumab can be considered as a recurrence prevention strategy in IBD patients with CDI.…”

Section: Medical Treatment Of CDI In Ibdmentioning

confidence: 99%

Management of Clostridioides difficile infection in patients with inflammatory bowel disease

Khanna

2021

Intest Res

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tered gut microbiota is colonization and infection with opportunistic microorganisms such as Clostridioides difficile. Studies over the years have demonstrated that the commonest infectious complication and the leading cause of a disease flareup in patients with IBD is C. difficile infection (CDI). 3 In contrast, non-C. difficile bacterial infections are uncommon in IBD patients with a disease flare. 4 Clostridioides difficile (formerly Clostridium difficile also known as C. difficile or C. diff) is an anaerobic Gram-positive spore forming bacterium that is ubiquitous in our environment. 5 Exposure to the C. difficile bacterium (spore or vegetative form) can lead to spectrum of outcomes ranging from no effect and no colonization to asymptomatic colonization to mild-moderate illness to severe diarrhea to fulminant lifethreatening infection. 6 It is now well-recognized that IBD patients are at a high risk of developing CDI even in the absence of other traditional risk factors. 3 In 2017, the American Gastroenterological Association released an expert clinical practice

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“…In a post hoc analysis of 44 MODIFY I/II participants with inflammatory bowel disease, treatment with bezlotoxumab showed a trend toward a protective effect when compared with placebo, although the wide 95% CI does not allow for firm interpretations before the conducting of more powered studies on this topic [26.7% (4/15) vs. 53.8% (7/13), with difference -27.2%, 95% CI -57.9 to 9.6] [61]. In 382 MODIFY I/II participants with cancer, the proportion of patients developing rCDI was lower in the bezlotoxumab (26/146, 17.8%) than the placebo arms (42/138, 30.4%), with an absolute difference of -12.6%, 95% CI -22.5 to -2.7 [62].…”

Section: Efficacy Of Bezlotoxumab In Phase 3 Rctsmentioning

confidence: 99%

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

et al. 2020

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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.

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Bezlotoxumab for Clostridium difficile Infection Complicating Inflammatory Bowel Disease

Cited by 15 publications

References 7 publications

The interplay of Clostridioides difficile infection and inflammatory bowel disease

The interplay of Clostridioides difficile infection and inflammatory bowel disease

Management of Clostridioides difficile infection in patients with inflammatory bowel disease

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

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