Treatment-emergent adverse events associated with Rebyota for Clostridioides difficile infection were more prevalent in those with renal comorbidities than in those without and were moderate in severity as well as related to pre-existing conditions.
Patients with renal comorbidities are at risk of severe Clostridioides difficile infection (CDI) and recurrence. Fecal microbiota, live-jslm (Rebyota [RBL]; Ferring Pharmaceuticals Inc.) is the first single-dose, rectally administered microbiota-based live biotherapeutic product to be approved by the FDA for the prevention of recurrent CDI (rCDI) in adults who follow standard-of-care (SOC) antibiotic treatment. An ongoing phase 3 trial, PUNCH CD3-OLS (NCT03931941), is evaluating the safety and efficacy of RBL in patients with renal comorbidities as well as assessing the outcomes of the treatment.
“Patients with renal comorbidity are at risk of CDI and recurrence. It is important to evaluate treatment options for these patients who are seen in clinical practice. Renal function is a key criterion for outcome of CDI,” said study author Glenn Tillotson, PhD, FIDSA, FCCP, of GST Micro LLC.
Participants enrolled in PUNCH CD3-OLS were aged 18 years and older with medically documented rCDI, with the first recurrence determined by the treating physician, and assessed with standard-of-card (SOC) diagnostic methods. A cohort of participants with renal comorbidity was identified from the medical history dictionary-derived terms in the modified intent-to-treat (mITT) population. Each patient received a single dose of rectally administered RBL after SOC antibiotics, with treatment being defined as recurrence-free for 8 weeks after treatment. Further, patients reported any treatment-emergent adverse events (TEAEs) through 6 months of treatment.
“Patients with renal disease are more susceptible to CDI and those with acute kidney injury are at increased risk of poor outcomes. This large study examined a bigger population of renally impaired patients than any other study,” said Tillotson.
Among the total 402 participants in the mITT group, 98 patients with adjudicated outcomes had a renal comorbidity, such as chronic kidney disease (n = 29) and end-stage renal failure (n = 5). Of the 98 participants, 50% had Charlson Comorbidity Index scores of greater than or equal to 5, compared to 18% without renal comorbidity. Treatment success was achieved by 66% (65 of 98 participants) and 77% (235 of 304 participants) with and without renal comorbidity, respectively.
“It has been shown that patients with chronic kidney disease have a disturbed gut microbiome and this undoubtedly contributes to poor outcome with CDI. On top of this dysbiosis, the administration of antibiotics or other drugs known to adversely affect the microbiome often make the patient more susceptible to CDI,” Tillotson noted.
Further, TEAEs were present in 71% (n = 70) and 64% (n = 194) of participants with and without renal comorbidity, respectively. Both groups presented moderate severity of TEAEs related to pre-existing conditions. In addition, serious TEAEs were reported by 16% (n = 16) and 8% (n = 24) of participants with and without renal comorbidity, respectively. The most commonly reported TEAE was CDI recurrence, which occurred in 3.1% (n = 3) of participants with renal comorbidity and 1.6% (n = 5) of participants without renal comorbidity.
“Clinicians who look after these patients need to have confidence that [RBL] can reduce the likelihood of recurrent infections. These data are similar to those seen in the registration study, PUNCH CD3,” said Tillotson. “[RBL] treatment success and TEAEs were numerically comparable for those with and without renal comorbidity. The moderate to severe events were considered to be related to pre-existing conditions. Reported AEs were generally GI in nature such as diarrhea, bloating, abdominal pain. An important point was the lack of bacteremia and fungemia in this population.”
Fischer, M, Thul, J, Guthmueller, B, et al. An Ad Hoc Subgroup Analysis of a Phase 3, Open-Label Study Indicates Efficacy and Safety of Fecal Microbiota, Live-jslm in Participants With Recurrent Clostridioides difficile Infection and Renal Impairment.