Faecal microbiota spores deliver benefit in older patients with C. diff recurrence

In an integrated analysis of two phase III ECOSPOR trials presented at AIBD 2023, faecal microbiota spores (ie, live-brpk) demonstrated favourable safety and efficacy signals for the treatment of recurrent Clostridioides (C.) difficile infection (CDI) in older individuals.

The analysis comprised patients from the ECOSPOR III and IV trials who received ≥1 dose of live-brpk. The randomized controlled ECOSPOR III study included 182 participants who had ≥2 CDI recurrences, while the open-label ECOSPOR IV enrolled 263 patients with recurrent CDI. In these studies, four capsules of live-brpk were administered over 3 consecutive days following antibiotic treatment. [AIBD 2023, abstract S77]

Through week 24, about two-thirds (63 percent) of participants reported experiencing treatment-emergent adverse events (TEAEs) that were mostly gastrointestinal and of mild-to-moderate intensity. The most frequent TEAE in ≥10 percent of patients was flatulence (24 percent), followed by diarrhoea (23 percent), fatigue (19 percent), and abdominal pain (18 percent).

According to the investigators, there were no serious TEAEs or deaths that were deemed related to the experimental agent, nor were there any study withdrawals owing to treatment-related TEAEs.

A similar pattern was observed in participants aged ≥65 years (n=183). The incidence of TEAEs was 64 percent, while the most common TEAEs were diarrhoea and flatulence (23 percent and 22 percent, respectively).

Overall, only 33 participants (9.5 percent) had on-study recurrence through week 8. This means that >90 percent of participants were recurrence-free by week 8. By week 24, the number was up by 20 (n=53) and the week-8 recurrence-free rate slightly dropped to 84.8 percent.

In the subgroup of participants aged ≥65 years, recurrent CDI rate through week 8 was 14 percent. This finding aligns with the initial ECOSPOR III report wherein the risk of recurrent CDI in patients aged ≥65 years who have received live-brpk on top of standard-of-care antibiotics was 17 percent. This was lower than the rate reported for those who were on antibiotics only (46 percent). [N Engl J Med 2022;386:220-229]

Live-brpk also delivered quality of life improvements as early as a week following treatment for up to 8 weeks. [JAMA Netw Open 2023;6:e2253570; Expert Rev Anti Infect Ther 2023;21:687-690]

Rapid microbiome restoration

Compared with younger adults, older adults are at greater risk for recurrent CDI. “In addition to microbiome changes associated with advanced age, risk factors may include number of comorbidities, reduced [immunity], and increased antibiotic exposure,” said the investigators.

Moreover, the risk of a consequent CDI event increases with the number of times a patient has CDI. [Clin Infect Dis 2021;73:755-757; Am J Gastroenterol 2021;116:1124-1147; Clin Microbiol Infect 2021;27(Suppl 2):S1-S21]

The researchers noted that antibiotics, though necessary to combat CDI recurrence, are inadequate for preventing recurrence due to their lack of efficacy against C. difficile spores, which germinate in a disrupted microbiome.

“Live-brpk is an oral microbiota-based therapeutic [for the prevention of recurrence] in adults with recurrent CDI by enabling rapid restoration of the microbiome … This integrated analysis confirms that live-brpk was well-tolerated and recurrent CDI rates were low, supporting early/rapid microbiome restoration in preventing recurrent CDI,” they said.

With no clinically important differences between the overall cohort and the subgroup of patients aged ≥65 years in terms of both safety profiles and efficacy outcomes, these results suggest that live-brpk may be considered for the management of recurrent CDI in a vulnerable elderly population at high risk for recurrent disease, said the researchers.