Per the American College of Gastroenterology (ACG), fecal microbiota transplantation (FMT) may be considered part of the treatment plan for patients with severe and fulminant Clostridioides difficile infections (CDI) refractory to antibiotic therapy, particularly, when patients are deemed poor surgical candidates (strong recommendation, low quality of evidence). The organization also recommends use of FMT to prevent second or further recurrence of CDI (strong recommendation, moderate quality of evidence). ACG recommends FMT to be administered via colonoscopy; however, this guidance was developed before the approval of Rebyota. Similarly, Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) recommend FMT only for patients with multiple recurrences of CDI who have failed appropriate antibiotic treatments. They emphasize appropriate screening of donor and donor fecal specimens, considering safety reports where recipients have become ill or died. This guidance predates Rebyota’s approval. [1], [2]
A recent review published in the American Journal of Gastroenterology in 2023 acknowledges RBX2660, now Rebyota (fecal microbiota-live jslm), as the first live biotherapeutic product (LBP) that provides uniformly sourced specimens from comprehensively screened donors and ensures a predictable safety and efficacy profile. Phase 2 and 3 trials (see Tables 1 and 2) have demonstrated the efficacy of Rebyota in improving sustained treatment responsiveness and long-term recurrence in patients with CDI. Use of Rebyota has been reported to be well-tolerated, with most gastrointestinal adverse events being mild to moderate in nature. Of note, patients with inflammatory bowel disease and irritable bowel syndrome were generally excluded from clinical trials to minimize confounding sources of diarrhea. Given its recent approval and the need for guideline updates, the authors proposed a list of use criteria for Rebyota elaborating on FDA-approved indication based on expert opinions and postulated risk factors (see Table 3). Despite the inherent differences between FMT and Rebyota, clinicians may still use the guideline recommendations for FMT to guide indications. For patients with several risk factors for recurrence, earlier commencement of Rebyota prior to a second recurrence may be reasonable in those with several risk factors for recurrence. In such a patient population, the natural regrowth of microbiota may have already been impaired, suggesting benefit from LBP supplementation. In practice, patient selection and treatment initiation should be individualized. While robust data are lacking, repeated Rebyota may be administered to those with a recurrence within 8 weeks of initial treatment. Given the low quality of evidence associated with FMT as treatment in patients with severe or fulminant CDI who are refractory to antimicrobial therapy and poor candidates for surgical intervention, further studies are required to elucidate the role of Rebyota as a novel agent for this challenging population. [3]
As with any new treatment, the authors stress the need for understanding the logistics of its usage, including shipment, handling, and administration in the facility or office, as specified in the product label and state regulations. If allowed, larger volume providers with a dedicated session and room for rectal administration along with patient scheduling may facilitate the smooth incorporation of Rebyota into practice sites. Overall, Rebyota provides a promising option in the settings of recurrent CDI and likely improves access to needed therapies as FMT becomes scarce. [3]
A 2023 cost-effectiveness analysis evaluated the cost-effectiveness of RBL compared to SOC for preventing rCDI using a Markov model developed in Microsoft Excel® from the perspective of a US third-party healthcare payer. Adult patients with ≥1 recurrence after CDI, completed oral antibiotics, or had severe CDI resulting in hospitalization within a year were included, while those with known rCDI history, IBD, IBS, chronic diarrhea, and previous FMT were excluded. The intervention involved RBL rectal suspension versus SOC after antibiotic therapy. RBL showed cost-effectiveness with an incremental cost-effectiveness ratio (ICER) of $18,727 per quality-adjusted life year (QALY) gained, $20,186 per life year gained versus SOC, and $13,727 per QALY gained for first recurrence patients. Improved QALYs, reduced healthcare resource utilization, and savings in medical costs contributed to RBL's cost-effectiveness. One limitation is that the study’s efficacy data was based on trials with a 24-month follow-up, and assumptions were made for long-term response, meaning real-world data is still needed. Nevertheless, investigators concluded that RBL is cost-effective compared to SOC at preventing rCDI with an ICER of $18,727 per QALY gained among patients with one or more rCDI. [4]