Peter L. Salgo, MD: There is another drug out there. This is bezlotoxumab. I practiced saying that. This has been approved in patients with a high risk of recurrence. Does it work? Does it prevent recurrences? How does it work? There are some clinical trials—the MODIFY I, MODIFY II. Then there’s this post hoc analysis by this guy named Gerding. How does this all fit together?
Dale N. Gerding, MD: Bezlotoxumab, I’ll call it bezlo, is a monoclonal antibody, humanized, and it has to be given intravenously. It is targeted at toxin B rather than amplify the microbiota or the microbiome to prevent C diff [Clostridioides difficile] infection. Here we’re working on the immune system and we’re providing antibodies against the toxin, in this case toxin B. Originally, this was a product developed for both antibodies to toxin A and toxin B, but it was found in the phase 3 trial that toxin B alone worked just as well as the combination. In a very large study—2500 patients in these trials, all ages, all severities, and all numbers of recurrences of C diff—the bezlo targeted at toxin B reduced recurrence rates from 27% in the placebo group to 17% in the all-treated patients.
The subsequent trial that I was the first author for looked at how you target this particular adjunct therapy. Remember, this is an adjunct. It’s added on to antibiotic therapy and it’s administered while antibiotics are being given. Its sole purpose is to reduce the recurrence rate. In the study that I worked on, the target there was to determine which type of patient is most likely to respond to the use of bezlotoxumab in terms of having a significant reduction of recurrence.
There were 5 preordained categories in the analysis. The categories were: patients aged over 65, those who have an immunosuppression, those who have a severe C diff infection, and those that have had C diff previously. When we looked at those, the fifth group was the 027 and078 specific strain of C diff,which did not turn out to be significant. For the other 4 groups, all of them had significant reductions in their recurrence rates. An important takeaway is if patients did not have any of these risk factors, first of all, they had a lower recurrence rate, but they did not appear to benefit from bezlotoxumab in terms of lowering it any further.
We now know that if patients have these risk factors, and particularly if they have multiple of these risk factors, the likelihood is very high that they’re going to have a high risk of recurrence, and that they’re going to respond to bezlo by lowering that risk. It is a different kind of therapy, an adjunct to standard antibiotic therapy. Again, price is an issue this one is clearly a way to reduce recurrence in high-risk patients.
Peter L. Salgo, MD: Joe Reilly, BS, PharmD, BCGP?
Joseph Reilly, BS, PharmD, BCGP: Similar to what we discussed with fidaxomicin, there are barriers to the use of bezlo, one of which being cost. This is another treatment option that seems to significantly decrease the recurrences in patients who had CDI [Clostridioides difficile infection] and also similar to fidax, which we should certainly be concerned about. The number needed to treat from that MODIFY I and II was about 10, therefore you have to treat 10 patients to prevent 1 recurrence. If we target certain patients, like those over the age of 65 or those that had a prior history of CDI in that study, that number needed to treat drops down to about 6. That’s critical. It was associated in those patients over 65, with a 51% less likelihood to have a recurrence. It is an impactful treatment option and, in my opinion, cost seems to be a barrier for using this drug.
Thomas Lodise, PharmD, PhD: The only thing I would add, too, is when we talk about recurrences, the 1 thing we have to acknowledge is we’re not getting down to 0, right? The 1 thing that’s going to come up is are you going to use bezlo with fidaxomicin. Peter Salgo, MD, I gave you a whole dissertation on how we need to change the way we view cost, but now you’re adding 2 premium priced agents.
There’s a nice publication that looked at what was that CDI therapy. As part of this, they showed a similar response, whether they got metronidazole, vancomycin, or oral fidaxomicin. One thing that jumps off the page when you look at that analysis; they only had 50 people who got fidaxomicin. I can acknowledge that being used as an argument as to the hypothetical question of: “Someone is getting fidaxo, even though they have a high risk for recurrence, am I still going to use bezlotoxumab?” The other thing within the trial is when they looked at it, it was mostly looking at 1 recurrence. We get people with these multiple recurrences. What do you do then? Do we still extrapolate the data there?
Even with fidaxomicin, most of the recurrence data is with 1 recurrence. I’m really looking forward to the publication of the Provisional Recommendations becoming finalized because I think they do a nice job showing the results over all the trials, the number needed to treat, and all the advantages that Joe Reilly, BS, PharmD, BCGP has mentioned. Even though I think we have some better data, we still have these gaps here in terms of these patients with multiple recurrences not getting down to 0. How do you support the argument using 2 premium priced agents when you only had 50 people who got fidaxomicin in the MODIFY trials?
Peter L. Salgo, MD: If you enjoyed this content, you should subscribe. We have an e-newsletter, and you can receive upcoming Peer Exchanges and other great content in your inbox—that’s right, electronically. I’ll see you next time. I’m Dr. Peter Salgo. Thanks again for watching.
Transcript Edited for Clarity