More real-world evidence bolsters role of bezlotoxumab in recurrent C. difficile infection

Bezlotoxumab (BEZ) proves to be effective at thwarting the return of Clostridium difficile infection (rCDI) in high-risk populations, namely individuals with one or more risk factors for recurrence and patients who are immunocompromised within 90 days and up to 24 weeks after initial infusion, respectively, according to two studies reported at the 2020 virtual IDWeek meeting.

A human monoclonal antibody against C. difficile toxin B, “BEZ is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in [high-risk] patients … outside of controlled trials,” according to Dr Tanner Johnson from the UCHealth University of Colorado Hospital in Denver, Colorado, US, who presented the first study.

Tanner and colleagues looked at real-world data of 120 patients (mean age, 55 years) with one or more risk factors for rCDI. Forty-seven received standard of care (SoC) treatment with oral vancomycin or fidaxomicin in combination with BEZ, while the 73 matched historical controls were treated with SoC alone. The mean number of lifetime CDI episodes was three, with 30.8 percent of the entire population having had severe CDI.

Within 90 days of treatment, significantly more patients who received SoC alone experienced recurrence (42.5 percent vs 12.8 percent). Add-on BEZ lowered the odds of recurrence by 80 percent (odds ratio, 0.20, 95 percent confidence interval [CI], 0.07–0.53; p≤0.01). BEZ effectiveness was independent of body weight, timing of administration, CDI severity, and prior receipt of faecal microbiota transplantation. [IDWeek 2020, abstract 789]

“The number needed to treat to prevent one [episode of recurrence] at 90 days was four,” Tanner said.

Meanwhile, there were no between-group differences observed in the incidence of all-cause mortality (2.1 percent vs 5.5 percent; p=0.67) and all-cause hospital readmission (42.6 percent vs 56.2 percent; p=0.20) at 90 days.

BEZ was well tolerated, and only a single patient developed infusion-related reaction. None of the BEZ-treated patients experienced heart failure exacerbations as opposed to two patients in the SoC group.

In light of the findings and despite the limited sample size and retrospective nature of data, Tanner asserted that BEZ could be a reasonable adjunct therapy in high-risk patient populations.

Sustained efficacy

Tanner and colleagues’ study, along with several others (eg, MODIFY I and II), established therapeutic efficacy within the first 12 weeks when the risk of recurrence is greatest, according to the presenting author of the second study, Dr Sarah Perreault of the Yale New Haven Hospital in Connecticut, US. [New Engl J Med 2017;376:305-317]

“However, the risk of rCDI can occur beyond the 12-week window in the immunosuppressed population,” Perreault noted.

Perreault and colleagues’ study added to current evidence by evaluating BEZ’s efficacy for up to 24 weeks after infusion. The analysis included 26 immunosuppressed patients (median age, 65 years; 58 percent female)—17 with haematologic malignancy, four with solid malignancy, four were kidney transplant recipients, and one with rheumatoid arthritis—at high risk of recurrence. These patients received 27 BEZ doses in real-world settings; one patient had two doses, which were administered 2 years apart.

Following BEZ treatment, only four rCDI episodes (15 percent) occurred: one at <4 weeks, two at 5–12 weeks, and one at 13–24 weeks. All were mild-to-moderate in severity, given that there was no evidence of colitis seen on CT scan and a median Zar score of 1. [IDWeek 2020, abstract 729]

High-risk antibiotics—such as fluoroquinolones, beta lactamase inhibitors, third generation cephalosporins, or carbapenems—were given in two patients who experienced recurrence and in 22 patients who had not.

The findings highlight the usefulness of BEZ in rCDI prevention in immunosuppressed patients even in the face of exposure to high-risk antibiotics, Perreault said.

Future studies should evaluate whether repeated BEV doses after 24 weeks are needed in this patient population, she added.