BEZLOTOXUMAB IS ASSOCIATED WITH A REDUCTION IN CUMULATIVE HOSPITALIZED DAYS: ANALYSIS OF THE HOSPITALIZATION DATA FROM THE MODIFY I AND II CLINICAL TRIALS
Clostridium difficile infection (CDI) is a serious recurrent diarrheal infection and is associated with increases in patient healthcare resource utilization because of both extended hospitalization and re-hospitalization. Recurrent CDI (rCDI) patients are significantly more likely to have a hospital readmission and spend increased time in inpatient settings. Clinical trials MODIFY I & II demonstrated that bezlotoxumab along with standard of care antibiotics (SoC) significantly reduced the incidence of rCDI compared to SOC alone (placebo) among patients with initial or rCDI. In a post hoc analysis, we used pooled data from the MODIFY trials to estimate the cumulative hospitalized days (all settings and intensive care units (ICU)) summed over the 84-day trial follow-up period.
We used hospital admission and discharge dates to generate daily patient record of inpatient hospitalization on any day from day of infusion through 84 days post-infusion. We used these data to estimate the probability of spending a day in the hospital using a logistic model. Lin’s (2000) method was applied where the daily average probability of spending a day in hospital among those non-censored was weighed by the probability of survival to obtain estimate of cumulative hospitalized days, adjusted for survival and censoring. Treatment effects were obtained using recycled predictions for the overall sample and for subgroups identified based on trial protocol and risk of rCDI. Standard errors, p-values, and 95% confidence intervals (CI) were obtained using 1000 bootstrap replicates. We repeated the analysis using patient admission to ICU to estimate cumulative ICU-hospitalized days (a cloglog model provided a better fit for the probability model).
The results for cumulative hospitalized days summed over an 84-day trial period, adjusted for censoring and survival, are provided in Table 1. Mean cumulative hospitalized days in the placebo arm (14.2 days) was greater than that for the bezlotoxumab arm (12.1 days). Overall, the mean difference between treatment groups was 2 days (CI: 0.3, 3.7). The mean difference was greatest for patients with clinically severe CDI (3.4 days). The difference in mean cumulative ICU-hospitalized days in the placebo vs. bezlotoxumab arm was 0.27 days (CI: -0.32, 0.87) about 13.4% of the difference in mean cumulative hospitalized days.
Bezlotoxumab is associated with reduction in total number of days spent in a hospital.