Live Microbiota Therapy Prevents Recurrent CDI in Older Adults with Comorbidity

Cirle A. Warren, MD

Credit: UVA School of Medicine

Fecal microbiota, live-jslm (REBYOTA) treatment is associated with maintained efficacy in older patients with multiply-recurrent Cloistridiodes difficile infection (rCDI), according to new phase 3 findings.¹

In post-marketing data presented at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, BC this weekend, a team of US-based investigators reported that Ferring’s live fecal microbiota therapy was associated with treatment success in approximately two-thirds of adults with rCDI and a comorbidity including cardiac or gastric disease, or chronic kidney disease (CKD).

The findings from the ongoing, open-label PUNCH CD3-OLS contribute another level of prescriber confidence with the first-of-its-kind agent for C difficile. Formerly known as RBX2660, REBYOTA was the first live microbiota treatment approved for the treatment of adult patients with rCDI, who had previously received antibiotic therapy, in November 2022.²

A rectally-instilled agent administered 1 – 3 days post-antibiotic course completion, the live microbiota therapy’s FDA application was supported by findings from the phase 3 PUNCH CD3 trial, in which 70.6% of patients administered the agent achieved treatment success per rCDI prevention through 8 weeks, versus just 57.5% of patients receiving placebo. On the heels of the FDA approval, experts including Andrew Skinner, MD, assistant professor of infectious disease and internal medicine at Loyola University, told HCPLive the addition of another adjunctive therapy for rCDI was going to have “major implications” for patients.³

However, he and colleagues were still considering where the agent fits into their armamentarium. Skinner noted the logistical issues surrounding similar discussions about the previously approved bezlotoxumab (Zinplava).

“Because it's seemingly a difficult thing to get set up for the patients to come in and get an infusion, cost can become an issue, etc,” Skinner said. “And we may end up running into something fairly similar when it comes to Rebyota at this point as well, in that maybe not, while we had discussed earlier, is that it may have some roles from a case-by-case for the first episode or second episode, I likely see it fitting somewhere in between the second and third episode, similar to where bezlotoxumab is at this point right now.”

In the PUNCH CD3-OLS data presented at ACG 2023, investigators led by Cirle A. Warren, MD, an infectious disease specialist with the University of Virginia, reported ad hoc subgroup analyses including older participants with rCDI and common comorbidities to the disease. “Advanced age and certain underlying comorbidities are among the risk factors for rCDI,” they noted.¹

The subgroup analysis included participants aged ≥65 years old with ≥1 comorbidity including cardiac disorders, CKD, and gastric disorders. Warren and colleagues sought a primary outcome of treatment success per absence of rCDI recurrence for 8 weeks following treatment that which proceeded an antibiotic course. They additionally monitored patients for rCDI recurrent, as well as treatment-emergent adverse events (TEAEs) for ≤6 months post-treatment.

The modified intent-to-treat population included 172 (43%) participants aged ≥65 years old with adjudicated outcomes. Among them, half (50%) had diagnosed cardiac disorders including atrial fibrillation and coronary artery disease; 53% had gastric disorders including gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS) and ulcerative colitis (UC); 16% had CKD. More than one-fourth (27%) patients were in ≥2 comorbidity subgroups; 8% were in all 3. Mean prior CDI episodes were ≥3 per patient across all subgroups at baseline.

Warren and colleagues observed a ≥63% treatment success rate across all 3 comorbidity subgroups: 63% for each of patients with cardiac disorders or CKD, and 70% for patients with gastric disorders.

Among 483 patients with eligible safety data, TEAEs occurred in 73% of patients with cardiac disorders, 70% of patients with CKD, and 65% of patients with TEAEs. A majority of reported TEAEs were deemed mild to moderate in severity.

“(Live microbiota therapy) treatment remains effective in a cohort of older participants with multiply recurrent CDI and common comorbidities,” investigators concluded. “The safety profile was consistent with that observed in previous clinical trials.”

References

1. ^{Warren CA, Tillotson G, Guthmueller B, Thul J, et al. P0181 - Efficacy and Safety of Fecal Microbiota, Live-jslm in Older Participants With Recurrent Clostridioides difficile Infection and Underlying Comorbidities: An Ad Hoc Analysis of an Open-Label, Phase 3 Study. Paper presented at: ACG 2023 Annual Scientific Meeting. Vancouver, BC, Canada. October 20 – 25, 2023.}
2. ^{Walter K. FDA Approves RBX2660, First Live Microbiota Treatment for Recurrent CDI. HCPLive. Published online November 30, 2022. https://www.hcplive.com/view/fda-rbx-2660-live-microbiota-treatment-recurrent-cdi}
3. ^{Johnson S, Reilly J, Cotto C, Skinner A. Advances in Microbiome-Based Therapies for Recurrent C difficile Infection: Role of Live-JSLM in Treating Recurrent CDI. HCPLive. Published online May 19, 2023. https://www.hcplive.com/view/role-of-live-jslm-in-treating-recurrent-cdi}