Bezlotoxumab Is Associated With a Reduction in Cumulative Inpatient-Days: Analysis of the Hospitalization Data From the MODIFY I and II Clinical Trials

Abstract

BackgroundPatients with recurrent Clostridium difficile infection (rCDI) are more likely to have a hospital readmission and spend increased time in inpatient settings compared with patients with primary CDI. MODIFY I and II demonstrated that bezlotoxumab significantly reduced rCDI vs placebo. A post hoc within-trial analysis assessed whether bezlotoxumab was associated with a reduction in cumulative inpatient-days.MethodsData were pooled from the MODIFY trials to estimate the cumulative hospitalized days summed over the 84-day follow-up period. We adjusted inpatient use data from pooled MODIFY I and II for survival and censoring to estimate 84-day cumulative inpatient-days, overall and for subgroups. Treatment effects were obtained using recycled predictions based on trial protocol and rCDI risk, and 95% confidence intervals were obtained using 1000 bootstrap replicates.ResultsMean cumulative inpatient-days were greater in the placebo arm (14.1 days) vs the bezlotoxumab arm (12.1 days) in the overall population. The mean difference between treatment groups was 2.1 days (95% confidence interval, –0.4 to –3.7). This was consistent in participants with risk factors for rCDI: age ≥65 years, compromised immunity, severe CDI, prior CDI, and ribotype 027/078/244 infection. As the number of risk factors increased, bezlotoxumab resulted in greater reductions in the number of inpatient-days compared with placebo (difference: –1.2 days, –2.3 days, –2.5 days, and –3.0 days for 0, 1, 2, and ≥3 risk factors, respectively).ConclusionsBezlotoxumab was associated with a reduction in cumulative inpatient-days, suggesting that treatment with bezlotoxumab may substantially reduce rCDI-associated health care resource use. Trial registrations. MODIFY I (MK-3415A-001, NCT01241552) and II (MK-3415A-002, NCT01513239)

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

“…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]. As shown in another analysis, the mean cumulative inpatient-days were lower in the bezlotoxumab (12.1 days) than the placebo arms (14.1 days), with a mean difference of -2.1 days (95% CI -3.7 to -0.4) [63]. An exploratory study investigated if human genetic variations are able to influence the effect of bezlotoxumab in patients enrolled in the MODIFY trials.…”

The Role of Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infections: A Review of the Current Literature and Paradigm Shift after 2021

“…The greatest reduction in inpatient days (−3.5 days) was observed in participants who presented with severe CDI at study entry. These results show promise for BEZ to reduce inpatient days, particularly for those with multiple risk factors for rCDI [ 38 ].…”

Fecal microbiota transplantation for recurrent Clostridioides difficile, safety, and pitfalls

“… 35 Furthermore, a post hoc analysis of hospitalization data from both MODIFY 1 and 11 trials showed that bezolotoxumab also resulted in reduction in cumulative inpatient days and CDI-associated re-hospitalizations. 36 , 37 …”