Exploratory Evaluation of Bezlotoxumab on Outcomes Associated With Clostridioides difficile Infection in MODIFY I/II Participants With Cancer

Abstract

Background The incidence of Clostridioides difficile infection (CDI) is reportedly higher and the cure rate lower in individuals with cancer vs those without cancer. An exploratory post hoc analysis of the MODIFY I/II trials (NCT01241552/NCT01513239) investigated how bezlotoxumab affected the rate of CDI-related outcomes in participants with cancer. Methods Participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI antibacterial treatment. A post hoc analysis of CDI-related outcomes was conducted in subgroups of MODIFY I/II participants with and without cancer. Results Of 1554 participants in the modified intent-to-treat (mITT) population, 382 (24.6%) were diagnosed with cancer (bezlotoxumab 190, placebo 192). Of participants without cancer, 591 and 581 received bezlotoxumab and placebo, respectively. In the placebo group, initial clinical cure (ICC) was achieved by fewer cancer participants vs participants without cancer (71.9% vs 83.1%; absolute difference, –11.3%; 95% CI, –18.6% to –4.5%); however, CDI recurrence (rCDI) rates were similar in cancer (30.4%) and noncancer (34.0%) participants. In participants with cancer, bezlotoxumab treatment had no effect on ICC rate compared with placebo (76.8% vs 71.9%), but resulted in a statistically significant reduction in rCDI vs placebo (17.8% vs 30.4%; absolute difference, –12.6%; 95% CI, –22.5% to –2.7%). Conclusions In this post hoc analysis of participants with cancer enrolled in MODIFY I/II, the rate of rCDI in bezlotoxumab-treated participants was lower than in placebo-treated participants. Additional studies are needed to confirm these results. Clinical Trial Registration MODIFY I (NCT01241552), MODIFY II (NCT01513239).

The Efficacy of Bezlotoxumab in the Prevention of Recurrent Clostridium difficile: A Systematic Review

“…0-2, 3-4, and greater than five days after onset) [2,3,37]. The proportion of patients developing rCDI in 382 MODIFY I/II participants with cancer was lower in the bezlotoxumab arms (26/146, 17.8%) than in the placebo arms (42/138, 30.4%), with an absolute difference of -12.6%, 95% CI -22.5 to -2.7% [38]. An exploratory study looked into whether human genetic variants can affect how bezlotoxumab works in patients included in the MODIFY trials.…”

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

“…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]. 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].…”

South African Society of Clinical Microbiology Clostridioides difficile infection diagnosis, management and infection prevention and control guideline

“…It requires further investigation. 101 Renal dysfunction: reduced rCDI rate in bezlotoxumab group (absolute reduction −17.1%; 95% CI −23.4 to −10.6). 102…”