Microbiota-Based Live Biotherapeutic RBX2660 for the Reduction of Recurrent Clostridioides Difficile Infection in Older Adults with Underlying Comorbidities

Background Advanced age and underlying comorbidities are associated with greater rates of recurrence in patients with Clostridioides difficile infection (CDI). Reducing the likelihood of recurrence through treatment with an antimicrobial followed by a microbiota replacement therapy can decrease the burden of this infection and improve patient outcomes. We report the efficacy and safety of RBX2660, a microbiota-based live biotherapeutic, in older adults with recurrent CDI, grouped by comorbidities. Methods In this post hoc subgroup analysis of the PUNCH CD3 trial, we assessed outcomes in older adults (age >= 65 years) grouped by Charlson Comorbidity Index severity scores at screening (moderate [3-4] and severe [>= 5]) and by the presence of underlying cardiac, renal, or gastrointestinal disorders. Results RBX2660 treatment success rates in older adults with comorbidities were consistent across subgroups and similar to those in the total RBX2660-treated population. A greater percentage of RBX2660-treated older adults remained free of CDI recurrence through 8 weeks following treatment compared with placebo-treated participants in all but 2 subgroups assessed. Across all subgroups, most treatment-emergent adverse events (TEAEs) were mild or moderate in severity and related to a preexisting condition. None of the serious or life-threatening TEAEs that occurred were related to RBX2660 or its administration. Occurrence of TEAEs did not cluster in any subgroup. Conclusions RBX2660 is efficacious and safe in older adults with recurrent CDI and underlying comorbidities. A post hoc subgroup analysis of the PUNCH CD3 phase 3 trial demonstrated the efficacy and safety of RBX2660 in medically complex patients with recurrent CDI, who are often encountered in clinical practice.