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

Abstract

Background: Patients 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.

Methods: Data 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.

Results: Mean 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).

Conclusions: Bezlotoxumab 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).

Keywords: CDI burden of disease; Clostridium difficile infection; recurrence; rehospitalization.

Figures

Figure 1.

Estimated mean cumulative inpatient-days summed over 84 days in the modified intent-to-treat population. aInpatients at the time of study randomization. bHistory of Clostridium difficile infection recurrence within the previous 6 months. cDefined on the basis of a subject’s medical history or use of immunosuppressive therapy. dZar score ≥2 based on the following: (1) age >60 years (1 point); (2) body temperature >38.3°C (>100°F; 1 point); (3) albumin level <2.5 mg/dL (1 point); (4) peripheral white blood cell count >15 000 cells/mm3 within 48 hours (1 point); (5) endoscopic evidence of pseudomembranous colitis (2 points); and (6) treatment in an intensive care unit (2 points). Abbreviations: CDI, Clostridium difficile infection; CI, confidence interval.