PACT Gastroenterology Center and Yale University School of Medicine New Haven, Connecticut
Introduction: Age and certain underlying comorbidities are among the risk factors for recurrent Clostridioides difficile infection (rCDI). Here, we report the efficacy and safety of RBX2660, a microbiota-based live biotherapeutic, in patients with rCDI grouped by age and baseline Charlson Comorbidity Index (CCI) severity scores. This is a subgroup post-hoc analysis of the PUNCH CD3 trial (NCT03244644), a prospective, multicenter, randomized, double-blind, placebo-controlled phase 3 trial.
Methods: Participants enrolled in PUNCH CD3 were ≥18 years old with documented rCDI and completed standard-of-care antibiotic therapy prior to treatment with RBX2660 or placebo. Treatment success was defined as remaining free of CDI recurrence 8 weeks after treatment. In this subgroup post hoc analysis, we assessed outcomes of participants grouped by age (< 65 years, 65 to < 75 years, and ≥75 years) and CCI severity scores at screening (0 to 2 [mild], 3 to 4 [moderate], and ≥5 [severe]). The treatment-emergent adverse events (TEAEs) were summarized for the double-blind treatment period within 8 weeks and censored if a patient received open-label RBX2660 after CDI recurrence.
Results: Of 262 total participants in the modified intent-to-treat population, 143 (55%) were < 65 years old, 68 (26%) were between 65 and < 75 years old, and 51 (19%) were ≥75 years old. A greater percentage of RBX2660-treated participants remained recurrence free through 8 weeks following treatment compared to placebo-treated participants in the following subgroups: < 65 years old with moderate and severe CCI severity scores; ≥65 years to < 75 years with mild, moderate, and severe CCI severity scores; and ≥75 years old with severe CCI severity scores (Figure 1A). In the total safety population (N=267), the overall incidence of TEAEs was 52% following RBX2660 treatment compared to 44% following placebo treatment, with mild events (mostly gastrointestinal) accounting for most of the difference. Similar percentages of participants categorized by age and CCI severity scores reported TEAEs (Figure 1B). Serious and life-threatening TEAEs did not cluster with any particular age or CCI subgroup and none were related to RBX2660 or its administration.
Discussion: RBX2660 is efficacious and safe in adults with rCDI regardless of age and baseline comorbidities.
