Randomized controlled trials had lower rates of success, but microbiota restoration still out-performed antibiotics.
A new meta-analysis of studies examining the use of microbiota restoration to treat recurrent Clostridioides difficile infection (CDI) found that resolution cure rates are lower in controlled clinical trial settings than in open-label and observational studies.
Even so, the data showed nearly three-quarters of patients in randomized controlled trials (RCTs) experienced resolution. The report was published in the journal Therapeutic Advances in Gastroenterology.
More than 50% of people who experience 2 or more episodes of CDI will experience a recurrence. While antibiotics remain the first-line therapy, patients who experience 2 or more recurrences are eligible for microbiota replacement therapy (MRT), a relatively new therapeutic option that involves restoring a healthy gut microbiome, explained corresponding author Sahil Khanna, MBBS, MS, of the Mayo Clinic, and colleagues. MRT generally takes one of 2 forms: fecal microbiota transplant or the use of a standardized live biotherapeutic.
Khanna and colleagues searched scientific databases to identify studies published up until July 2022 in which patients with recurrent CDI were treated with microbiota restoration and clinical resolution data after one dose were available.
The authors found 19 studies that met their inclusion criteria. In total, those 19 studies enrolled 1176 patients with recurrent CDI. Overall, the weighted pooled rate (WPR) of clinical cure after a single dose was 78% (95% CI, 71%-85%). However, the authors said there was significant variance between study types.
In studies with a control arm, the WPR was 72% (95% CI, 60%-82%). In open-label trials, the WPR was 84% (95% CI, 74%-92%). When the authors directly compared resolution rates in RCTs to those of open-label trials, they found the latter had a higher cure rate (84% WPR for open-label trials, versus 73% for RCTs).
“In this study, we demonstrate that the efficacy of microbiota restoration for recurrent CDI was lower in trials with a comparator group compared to open-label trials of MRT,” Khanna and colleagues wrote. However, they cautioned that the included trials had significant differences in methodology, including the route of administration and type of MRT used. As a result, they said, their findings may not be generalizable.
Discussing potential reasons for the difference in cure rates between RCTs and open-label trials, the authors hypothesized that the strict inclusion and exclusion criteria used for controlled trials was one likely cause.
Still, even though MRT had a lower success rate in RCTs, the authors said its cure rate was still significantly higher than that among patients receiving antibiotics. Among the 10 trials that included control arms, the WPR among patients receiving antibiotics was just 52% (95% CI, 43%-60%).
The authors noted that the current analysis is based on studies of recurrent CDI, but they said more studies are needed to better understand how well the therapy works in specific subgroups, such as severe and fulminant CDI. The early data, they said, are positive. They also said future trials ought to look at patients with comorbidities like irritable bowel disease (IBD).
“Given that most of the trials have excluded patients with concurrent IBD and patients taking antibiotics, it would be interesting to assess the efficacy of MRT among those high-risk patients,” they wrote.
In the meantime, the authors said despite the difference between RCTs and open-label trials, the overall evidence supports the use of MRT.
“Newer data from clinical trials are extremely promising for the use of MRT for recurrent CDI,” they concluded.
Tariq R, Pardi DS, Khanna S. Resolution rates in clinical trials for microbiota restoration for recurrent Clostridioides difficile infection: an updated systematic review and meta-analysis. Therap Adv Gastroenterol. 2023;16:17562848231174293. Published 2023 May 30. doi:10.1177/17562848231174293