Analysis of C. difficile infection–related outcomes in European participants in the bezlotoxumab MODIFY I and II trials

Abstract

The MODIFY I/II trials demonstrated that bezlotoxumab, a human monoclonal antibody against Clostridioides difficile toxin B, given during antibiotic treatment for Clostridioides difficile infection (CDI) significantly reduced C. difficile recurrence (rCDI) in adults at high risk for rCDI. Efficacy of CDI-directed intervention may depend on ribotype regional epidemiology, and patient characteristics. This post hoc analysis assessed the efficacy of bezlotoxumab in the subgroup of MODIFY I/II trial participants enrolled in Europe. Data from the bezlotoxumab (10 mg/kg single intravenous infusion) and placebo (0.9% saline) groups from MODIFY I/II were compared to assess initial clinical cure (ICC), rCDI, all-cause, and CDI-associated rehospitalizations within 30 days of discharge, and mortality through 12 weeks post-infusion. Of 1554 worldwide participants, 606 were from Europe (bezlotoxumab n = 313, 51%; placebo n = 292; 48%). Baseline characteristics were generally similar across groups, although there were more immunocompromised participants in the bezlotoxumab group (27.2%) compared with placebo (20.1%). Fifty-five percent of participants were female, and 86% were hospitalized at randomization. The rate of ICC was similar between treatment groups. The rate of rCDI in the bezlotoxumab group was lower compared with placebo among European participants overall, and among those with ≥ 1 risk factor for rCDI. Bezlotoxumab reduced 30-day CDI-associated rehospitalizations compared with placebo. These results are consistent with overall results from the MODIFY trials and demonstrate that bezlotoxumab reduces rCDI and CDI-associated rehospitalizations in European patients with CDI. MODIFY I/II (NCT01241552 and NCT01513239)

Genomic epidemiology and transmission dynamics of recurrent Clostridioides difficile infection in Western Australia

“…However, studies have shown that the 8-week interval does not allow sufficient discrimination of relapse and reinfection; for the majority of relapsing CDI cases confirmed by conventional PCR ribotyping, the time between initial and second episode ranged from 4 to 26 weeks (average 12 weeks) [ 12 , 29 ]. Acknowledging this limitation, studies from the USA [ 33 ], Europe [ 11 ] and Australia [ 29 ] have used a longer 12-week cut-off. In this study, 48% of WGS-confirmed relapses occurred beyond the 8-week (56-day) cut-off and, of these, 19% occurred beyond 12 weeks (84 days).…”

“…CDI cases were defined as having diarrhoea with a positive faecal PCR for tcdB using the BD GeneOhm™ or BD MAX™ platforms. For this study, and in line with recent phase III MODIFY trials [ 10 , 11 ], rCDI was defined as two or more episodes of diarrhoea accompanied by a positive C. difficile stool assay within a 12-week period. C. difficile isolates from rCDI patients were characterised by PCR ribotype (RT) and toxin genotype ( tcdA , tcdB and cdtA/B ) as previously described [ 16 ].…”

“…Clinical practice guidelines recommend that if the time elapsed between two episodes of CDI is > 8 weeks and that prior symptoms have resolved with or without therapy, then, the second episode is classed as a new infection as opposed to a recurrent infection [ 9 ]. Recent phase III clinical trials for bezlotoxumab (MODIFY I and II) used a longer, 12-week cut-off to define rCDI [ 10 , 11 ].…”

Clustering Disease of Clostridioides Difficile Infection: Implication for the Management in Internal Medicine

“…Bezlotoxumab is a recombinant human monoclonal antibody IgG1/kappa isotype, effective as adjunctive treatment in patients at high risk of recurrence of CDI [43]. Specifically, bezlotoxumab blocks the action of CD B toxin (tcdB) with a significantly reduced relapse rate in patients with recurrence risk factors (older age, extensive antibiotic use) [44][45][46][47]. Currently, bezlotoxumab is recommended to prevent the recurrence of CDI, although it is currently difficult to establish which parameters predict the possibility of recurrent infection or which are the factors that generate short-term recurrence of CDI [48,49].…”

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

“…ICC was similar between groups (BEZ 82.4% vs. placebo 81.2%: 95% CI, 1.2 [−5.0 to 7.4]). Participants in the BEZ group had lower rates of CDI-related rehospitalization within 30 days of discharge compared to the placebo group (4.9% vs. 14.8%, respectively), and all-cause rehospitalizations and the proportion of participants who died within 30 days or 90 days of randomization were similar between the BEZ and placebo groups (23% vs. 26.6%, 5.1% vs. 5.1%, and 9.9% vs. 10.5%, respectively); however, statistical analyses of these results were not performed [ 39 ].…”