In this podcast, Dr Edward Barnes discusses the highlights from his presentation on Immune Mediated Events Related To Medications from the Advances in Inflammatory Bowel Disease regional meeting September 25.

Edward Barnes, MD, is an assistant professor of medicine and gastroenterologist at the University of North Carolina at Chapel Hill.

TRANSCRIPT

Hi, I'm Ed Barnes from the University of North Carolina. At the AIBD Regionals conference, I had the pleasure of talking about immune-mediated events related to medications.

One of the exciting things about the emergence of immune-mediated therapies is that we've seen improvements in the way that we treat malignancies, and autoimmune conditions, and immune-mediated disorders with the targeted therapies that are targeting the immune system.

One of the adverse effects or downsides of those that we see as gastroenterologists is that up to two-thirds of patients can experience some sort of adverse effect related to these immune-mediated therapies.

In part, when we think about patients that are treated first with malignancy with potentially like a checkpoint inhibitor, up to two-thirds of patients would experience some sort of adverse event related to these therapies.

The one that we encounter as gastroenterologists are often either a gastroenteritis, or an enterocolitis, or an immune-mediated diarrhea or colitis. This is where we come to involve patients that are treated with these therapies for malignancies.

The most common therapies that we encounter for the treatment of malignancies are the anti-CTLA-4 or the anti-PD-1 therapies. I talked a lot about this today because these are the therapies that are often associated with development of diarrhea or colitis. Again, the ones that we'll encounter as gastroenterologists.

Our role as gastroenterologists has emerged in this field as these have become more widespread therapies for the treatment of either melanoma, or renal cell carcinoma, or non-small cell lung cancer.

The way that we often become involved is those patients that have more severe disease, grade two or higher disease, often require a colonoscopy. The colonoscopy becomes very important for the gradient of the disease and becoming a risk stratification to decide how those patients should be treated.

If you have grade two or higher disease and you have high-risk factors such as deep ulcers or more extensive disease, often, the way we often grade patients with Crohn's disease or ulcerative colitis, to be quite frank, those are the patients that we think about being at greater risk.

Those are the patients that will often be started on higher-dose steroids. If they're refractory to steroids, they're often treated with therapies that we use for the treatment of inflammatory bowel disease, either infliximab or vedolizumab.

The good news for us as gastroenterologists is that we get to be involved with these patients, and this can often be a place where we can offer a therapy that's often effective. Usually within two to three doses of the use of infliximab or vedolizumab, patients will turn around with these immune-mediated diarrhea or colitis very quickly.

This is important because these are patients often, as I mentioned before, that have an underlying malignancy, and so we want to treat the colitis, treat the underlying enterocolitis so they can get back on resuming their therapies.

This is a rapidly emerging area of research and of clinical care and one that you've probably encountered in your practice already. This is one where the evidence is, I would say, catching up to what we're doing in clinical practice.

There's evidence that's emerging at every scientific meeting, and one that I think we all want to keep our eye on as practicing gastroenterologists.

Another topic that I talked a little bit about during our meeting today is, what about therapies that don't cause something that looks like IBD? What about immune-mediated therapies that cause a de novo Crohn's disease or a de novo ulcerative colitis?

One of the ones that's been commonly reported in case reports at least, and one that I've seen in my clinic, is the use of anti-IL-17 therapies that are often used in psoriasis or psoriatic arthritis that lead to the development of Crohn's disease or ulcerative colitis.

What's interesting about this is that this has been shown in case reports, but often not reproduced in larger studies where they've pooled either clinical trials of anti-IL-17 therapies or they've pooled large nationwide cohorts to look at the rates of development of IBD in patients that are treated with anti-IL-17 therapies.

This is something to certainly keep your eye on in practice. Whether or not this is a true, true relationship where anti-IL-17 therapies lead to de novo Crohn's disease or ulcerative colitis in patients that are at risk, the jury's still out and it's something that we certainly will have an interesting discussion about.

The other two topics that I touched on briefly, or something that we see in practice when we're treating patients with Crohn's disease and ulcerative colitis, that being anti-TNF psoriasis and anti-TNF-induced lupus. We touched a little bit about why these might occur and how we might manage these patients, because these are common presentations.

If we're using anti-TNF therapies effectively in the treatment of Crohn's disease and ulcerative colitis, when's the right time to continue the therapy, and when do we need to stop that?

How do we make this decision in conjunction with our dermatologists, if the patient has psoriasis, or in conjunction with our rheumatologists, if the patient has developed anti-TNF-induced lupus?

The disparity sometimes between the two is that often, if a patient has anti-TNF-induced psoriasis, up to 52% of patients will develop psoriasis again if you use an anti-TNF the second time around.

This may not be true in patients that develop anti-TNF-induced-lupus, and you may be able to re-challenge them with a second anti-TNF if you want to because an anti-TNF was effective. Again, this has to be a decision you make in conjunction with your rheumatologists.

All of these cases probably illustrate that the treatment of immune-mediated disorders is not something that's done in a silo. This is becoming a very multidisciplinary field, as you're all aware. This is one of the exciting things about treating patients that have these immune-mediated disorders, because we all have to work together to get the right outcome.

This is why I was excited to talk about this today. Certainly, I hope that this discussion was helpful for you and prompts you to have these exciting multidisciplinary or interdisciplinary conversations to improve the care of your patients as well. Thank you very much for your interest, and I hope this was helpful.