PHILADELPHIA – , according to a randomized controlled trial.
“Given the high efficacy of FMT, the addition of bezlotoxumab may not provide a further reduction in CDI recurrence,” said study author Jessica R. Allegretti, MD, MPH, AGAF, with Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Allegretti presented the findings during a plenary session at the annual meeting of the American College of Gastroenterology (ACG).
Brigham and Women's Hospital
Dr. Jessica R. Allegretti
Common and Deadly
CDI is the most common cause of healthcare-associated infection in the United States, leading to roughly 4.8 billion in excess healthcare costs. There are an estimated 500,000 cases each year in the United States, with roughly 30,000 of those cases leading to death.
Patients with IBD have a prevalence of CDI that is 2.5- to 8-fold higher than in peers without IBD, and they also have 4.5-fold higher risk of recurrence. Sequelae of CDI in IBD include exacerbations of IBD, increased hospitalizations, escalation of IBD therapy, and colectomy.
FMT has been shown to be safe and effective in patients with IBD and rCDI.
Bezlotoxumab — a fully human monoclonal antibody that binds to C difficile toxin B — was approved by the US Food and Drug Administration (FDA) in 2016 to reduce the recurrence of CDI in patients aged 18 years and older.
However, there is only limited data on the value of combining these two strategies.
Allegretti and colleagues conducted a multicenter randomized controlled trial to evaluate the impact of FMT in combination with bezlotoxumab in patients with IBD and rCDI.
They enrolled 61 patients (mean age, 38 years, 54% men) with two or more episodes of CDI who received a single colonoscopic FMT. Twenty patients had Crohn’s disease, and 41 had ulcerative colitis.
Thirty patients were randomly allocated to receive a single bezlotoxumab infusion and 31 to receive a placebo infusion prior to FMT.
A total of five participants (8%) experienced a CDI recurrence with confirmed EIA+ stool –4 in the treatment group and 1 in the placebo group (13% vs 3%, P = .15).
Participants in the treatment group had higher odds of CDI recurrence, though this was not statistically significant (odds ratio [OR], 4.6; 95% CI, 0.5-43.9), Allegretti reported.
With regards to C difficile colonization, more patients in the treatment group were decolonized compared with placebo at week 1 (82% vs 68%, P = .22) and at week 12 (83% vs 72%, P = .34).
Steroid use at the time of FMT was associated with a significant increased risk of ongoing colonization of C difficile at week 12 post-FMT (OR, 4.90; 95% CI, 1.18-20.37; P = .03).
While there were no significant differences in IBD outcomes between groups, there were numerically higher rates of IBD improvement in the treatment group compared to the placebo group 56% vs 46%.
Only one patient had IBD worsen, and this patient was in the placebo group. There were no de novo IBD flares.
FMT alone and with bezlotoxumab were both safe and well tolerated. Two serious adverse events were reported; neither were deemed to be treatment-related.
“This is the first clinical trial to assess the clinical effect of FMT in combination with bezlotoxumab in patients with IBD and rCDI. The data suggest no clear efficacy benefit to this combination compared to FMT alone,” Allegretti told attendees.
“This finding is not surprising given the high rate of efficacy of FMT,” said Ashwin N. Ananthakrishnan, MD, MPH, AGAF, with Massachusetts General Hospital and Harvard Medical School, Boston, who was not involved in the study.
Dr. Ashwin N. Ananthakrishnan
“It would have been interesting to compare bezlotoxumab vs FMT as primary treatment for recurrent CDI in this population,” Ananthakrishnan added.
This was an investigator-initiated study funded by Merck. Allegretti disclosed various relationships with Abbvie, Artugen, Bristol Myers Squibb, Ferring, Finch Therapeutics, Janssen, Merck, Pfizer, and Seres. Ananthakrishnan had no relevant disclosures.
A version of this article first appeared on Medscape.com.