Burden of C. Difficile and Novel Therapies

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EP: 1.Burden of C. Difficile and Novel Therapies

EP: 2.Objectives of Cost Effective Analysis

EP: 3.Defining Standard of Care

EP: 4.Target Population In Analysis

EP: 5.Cost Inputs and Key Data from Analysis

EP: 6.Study Limitations and Relevance

Dr.Paul Feuerstadt: Hello and welcome to this Managed Healthcare Executive Between the Lines program that focuses on the article “Cost-Effectiveness Analysis of Rebyota Cost-Effectiveness Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) Versus Standard-of-Care Antimicrobial for the Prevention of Recurrent Clostridioides difficile Infection in the USA.” The objective of this program are to focus on the article by Lodise et al. in a journal club style. We’re going to cover a bunch of different things. We’ll cover a background and overview, the methods of this specific study, the results, and most importantly the relevance. My name is Dr. Paul Feuerstadt and I’m an assistant clinical professor of medicine at the Yale University School of Medicine and an attending gastroenterologist at the PACT Gastroenterology Center. And I’m so delighted to be joined by Dr. Michael Kobernick. Michael, can you introduce yourself

Dr. Michael Kobernick: Sure. Thank you Paul. Really nice to be here today with you on this program. I’m a senior medical director at Blue Cross of Michigan, where I work in large measure with employer groups, advising them on how to manage healthcare benefits externally and internally, I work on all things coverage related as well as new market solution. The focus of my work really is population health, defining value as the relationship between cost and outcome. We’re going to talk a lot about outcome today. I look forward to our conversation.

Dr. Paul Feuerstadt: And I’m really delighted that we have both the clinical side, the payer side, and from your standpoint, the payer and the clinical side. So, it’s wonderful that we’re going to have dialogue around this really important study.

Dr. Michael Kobernick: Yes. Thank you.

Dr. Paul Feuerstadt: So let’s go ahead and get started and let’s talk about C. diff infection. C. diff is a major problem in the United States. In fact, it is the most common healthcare associated infection. On an annual basis, it’s estimated at 365200 people are diagnosed with this so it’s a massive burden on our healthcare system. That burden isn’t just the abdominal pain and diarrhea that we see in patients with C. diff. The burden extends further. It extends to what it portends over the next 12 months. There’s very nice data that show that the more episodes of C. diff that patients have, the higher frequency they have for sepsis and colectomy. With one single episode of C. diff, about 16.5% of patients will be diagnosed with sepsis within 12 months and 4.6% will have their colon resected. One we get to three-plus episodes of C. diff, wow, 43.3% of those patients will be diagnosed with sepsis within 12 months and 10.5% will have a colectomy. Speaking to what this diagnosis portends but also speaking to the importance of recurrence, recurrence is a major issue for individuals that get diagnosed with C. diff because even if they get appropriate standard of care antimicrobials, up to 35% will have a recurrence within about eight weeks. Of those, 40% will go on to recur after that and up to 65% thereafter as patients get caught in this vicious cycle. That vicious cycle also leads to psychological impact on patients. That psychological impact includes post-traumatic stress disorder, depression among other things. So as with any disease, the more you understand, the more we understand the impact on patients, the more we will try our best to optimize therapy and shut down recurrences. Of course, what comes with recurrences, what comes with post-traumatic stress disorder, what comes with sepsis and colectomy are significant financial drains on the healthcare system.

That’s largely what this study is looking at which is an advancement of therapeutics that could decrease rates of recurrence in the future. Now…to understand the ways that we can optimize therapy; we have to understand the infection. There’s two main phases of the infection: the spore phase and the vegetative phase. As a clinician, we largely … think about the vegetative phase of infection because that’s the phase that releases toxins causing the abdominal pain and diarrheal syndrome that we see. Antimicrobials, they control that vegetative phase; vancomycin, fidaxomicin. This is why when patients are on antimicrobials, when they have C. diff, they are largely asymptomatic. What’s missing from this picture is the second half of the story which is the microbiota. When patients get diagnosed with C. diff, they have deficiencies of their microbiota. When we treat, we’re not really treating those deficiencies of the microbiota. We’re just controlling the vegetative phase. If we pull off the antimicrobial, it’s up to that microbiota to regrow. When the microbiota regrows, sometimes it doesn’t regrow quite as quickly as we need to give the spore phase that knockout punch. When it doesn’t regrow appropriately or as quickly as we want, a recurrence occurs. So optimizing therapy is essential and using treatments like vancomycin or fidaxomicin will optimize the antimicrobial side.

Now, the IDSA [Infectious Disease Society of America] guidelines updated themselves in 2021, preferentially recommending fidaxomicin. Why? Because it has a less impact on the surrounding microbiota and is associated with decreased rates of recurrence so fidaxomicin is preferred, vancomycin is an acceptable alternative. The same holds true for first recurrence but as we approach these patients, we also have to understand that there are demographical risk factors for recurrence, medication risk factors for recurrence and environmental. As we contextualize that information, add on therapies such as microbiota restoration or so-called, fecal microbiota transplantation and a product called bezlotoxumab can really help us as clinicians. Bezlotoxumab is a fully humanized monoclonal antibody designed to bind toxin B in a specific way. It’s an infusion given during the standard of care antimicrobial and it’s associated with decreased 90-day recurrence rates. So that is one guideline based treatment that we can give in addition to the standard of care antimicrobial to decrease future recurrence. What we’re going to focus on today is microbiota restoration or replenishment of the microbiota after vancomycin or fidaxomicin.

There have been a number of foundational trials over the [past] decade that have shown that this is incredibly effective but we’re now stepping into the future. In November 2022 and April 2023, the FDA approved the first live biotherapeutic products. These are products that target the microbiota, replenish the deficiency seen with C. diff infection and are associated with decreased rates of recurrence. Both products had encouraging phase three data that showed both safety and efficacy for the product. What we’re going to focus on today is fecal microbiota live JSLM, trade name Rebyota and we’ll call it RBL for the purposes of this discussion because RBL is the focus of the study that Tom Lodise [of the Albany College of Pharmacy and Health Sciences, in New York] and colleagues put forward as a cost-effectiveness analysis for RBL in patients.

Transcript is AI-generated and edited for clarity and readability.