Optimizing Treatment Strategies to Manage Inflammatory Bowel Disease - Episode 15
Jessica Allegretti, MD, MPH, and Edward Loftus Jr., MD, review emerging agents in the later phases for the management of IBD.
Remo Panaccione, MD, FRCPC: Does anything else catch your eyes, Ed or Jessica?
Jessica Allegretti, MD, MPH: I’m most excited for, at the current moment, the selective JAKs to be coming down the line, especially for Crohn disease. That’s really what I have my eye on, in addition to, as Bill just mentioned, the IL-23 inhibitors. Those are the things that are coming the soonest, and I’m excited to have more hopefully safe and efficacious options when treating Crohn disease. Those are what I have my eye on, in addition to, of course, my personal biases: the microbiome therapeutics, of which there are several under investigation. We did see some intriguing initial data from Seres Therapeutics in 1 of their agents in the treatment of ulcerative colitis, although these are still very early days. We also know there are several companies working on FMT [fecal microbiota transplantation]–like products, but really more selective microbiome therapeutics. I’m very excited for those. The positioning of microbiome therapeutics earlier or in combination with other advanced therapies is really exciting.
Remo Panaccione, MD, FRCPC: Ed, do you have any final words on therapies?
Edward Loftus Jr., MD: Some of the etrolizumab UC [ulcerative colitis] results were clearly mixed and somewhat disappointing, but don’t forget, we still have a Crohn [disease] trial out there. At some point, we’re going to have some anti-integrin data, and more on Crohn, so there may be something. There are a few other molecules in that realm, so who knows what will happen?
William Sandborn, MD: In that same vein, there’s an orally systemically bioavailable alpha(4) beta(7) [LPAM] inhibitor that’s a small molecule. Think of it as oral vatelizumab. That’s in phase 1 testing. Then there’s another that’s a short peptide that gets down into the more distal gut, and you can think of it as inside out instead of outside in. We always knew that vatelizumab didn’t work solely the way it was proposed because, at doses and drug concentrations that are one-tenth of what’s required for clinical efficacy, you can completely saturate the alpha(4) beta(7) receptors on the appropriate lymphocytes in the periphery. If the entire mechanism of action of vatelizumab is blocking lymphocyte trafficking from the periphery to the gut, then that should be sufficient for efficacy, and it’s not. It makes you think that there’s some other mechanism beyond that, possibly with an antibody in the tissue affecting cell-cell interactions of cells that have already trafficked. With this inside-out peptide, you can see efficacy, and they saw it in a pilot study in the clinic, as well as in animal models, at concentrations where you got some into the blood but only to the point that it was 60% saturating the receptor in the periphery. You wouldn’t expect that to work, yet it did. Anyway, I’m with that. We’re going to see an evolution in anti-integrins and maybe oral therapies. Wouldn’t that be cool?
Remo Panaccione, MD, FRCPC: That’s a lot to unpack and look forward to. With that, I want to thank everyone for the rich and informative discussion. Before we conclude, I’d like to get some final thoughts from each of you about what you’d like to say to our clinical colleagues. What should they be striving for in treatment and looking for the future? Jessica, why don’t we start with you?
Jessica Allegretti, MD, MPH: As we’re evolving in this space, it can potentially feel a bit overwhelming. There are almost too many potential choices coming down the line, so what I would tell my colleagues is to assess your patients. Look for prognostic factors to help you make those treatment decisions, pick targets that you’re going to follow, and do that systematically with your patients every time. It’s going to be different for every patient, but really that’s a way to keep things straight and organized. Stay attuned to the data and all these exciting developments coming down the pipeline. Remember, you can always lean on some of your colleagues at IBD [irritable bowel disease] centers if you’re unsure about therapies or want assistance. For example, I’m always happy to have discussions with my colleagues about which agent we should be choosing, why, or if they’re uncomfortable with potential therapeutic options, because until you have a lot of hands-on experience with some of these drugs, it takes a bit to get comfortable with them. That would be some of my advice to anybody out there treating IBD, but it’s starting to feel a bit overwhelming by all these new advances coming down.
Remo Panaccione, MD, FRCPC: Ed, do you have parting shots?
Edward Loftus Jr., MD: I’m going to a total side thing. We’re seeing patients with complicated diseases. One of our jobs is to stay rational but also project confidence and hope. Sometimes, we see these patients who have lost hope. Usually, for almost every patient, there’s something you can do to improve their quality of life. Just keep that in mind.
Remo Panaccione, MD, FRCPC: Excellent.
Jessica Allegretti, MD, MPH: Agreed.
Remo Panaccione, MD, FRCPC: Bill?
William Sandborn, MD: We’re at the end of the beginning of the revolution of IBD therapy. Buckle up—a lot of new stuff will come, but we have an amazing repertoire of therapies that we can use today. Be students of the field and the craft, and learn to use those therapies and, as Ed said, improve the lives of your patients.
Remo Panaccione, MD, FRCPC: I always say to the fellows here [Cumming School of Medicine at the University of Calgary], “We need to demand more.” We need to demand more of ourselves to help the patients, demand more of science to push things forward to improve the lives of the patients and to pay attention to those little things that we’ve all talked about tonight. Ed summed it up nicely, that even if you’re on your fourth biologic or advanced therapy, there’s something you can do for that patient that will make tomorrow better for them. Always look at what you can do for that individual patient. With that, to all of you, this was just fantastic stuff. I hope the audience enjoyed it.
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Transcript edited for clarity.