In this video, Dr Hanauer, from the Feinberg School of Medicine at Northwestern University in Chicago, reviews his presentation at the Crohn's & Colitis Congress 2021 on "evolutionary" agents on the horizon for treatment of inflammatory bowel disease.

Stephen B. Hanauer, MD, is the Clifford Joseph Barborka Professor of Medicine in gastroenterology and hepatology at the Feinberg School of Medicine at Northwestern University in Chicago, Illinois.

TRANSCRIPT

Hello, I'm Dr. Steve Hanauer from Northwestern University in Chicago. I'm very pleased to have presented a discussion on emerging therapies for inflammatory bowel disease.

Here we are in the beginning of 2021, and we have multiple mechanisms for patients with both ulcerative colitis and Crohn's disease. For the most part, we're speaking about the advanced options beyond the foundational therapies of mesalamine, corticosteroids, and traditional immunomodulatory agents.

For patients with moderate-to-severe ulcerative colitis and Crohn's disease, the majority have the option of either steroids with immunosuppressives; a TNF inhibitor with or without an immunosuppressive; ustekinumab, an IL-12/23 inhibitor, with or without an immunosuppressive; vedolizumab, an antiadhesion molecule with or without an immunosuppressive; or tofacitinib without immunosuppression in the setting of ulcerative colitis for patients who have not had an adequate response to TNF inhibitors.

I do not go into the detail of the use of these individual agents. What is forthcoming are agents that will be evolutionary to our current therapeutic mechanisms of action. I would envision, in the next year or 2, several of the current mechanisms may be superseded by safer and somewhat more effective therapies.

For instance, the IL-12/23 approach with ustekinumab has been very effective in ulcerative colitis and Crohn's disease, but with recognition that inhibition of interleukin-23 alone has been effective in both UC and Crohn's disease. There may be added benefit for this type of therapy, but that remains to be determined.

Nevertheless, there are several IL-23 inhibitors that are in the process or completing phase 3 studies that look to be both safe and somewhat more effective for patients with Crohn's disease, particularly those who have had an inadequate response to prior treatment with TNF inhibitors.

This group of individuals who have failed TNF inhibitors have had an abrogated response compared to TNF-naive patients with both ustekinumab, vedolizumab, and tofacitinib. Another mechanism of action that has been somewhat upgraded, let's say, is Janus kinase inhibition.

There are several oral JAK inhibitors that have somewhat greater specificity than tofacitinib, and look to be somewhat safer and equal or somewhat better than tofacitinib in the setting of Crohn's disease, and also possibly ulcerative colitis. Both filgotinib and upadacitinib are completing their phase 3 studies and look to be promising in the relatively near future.

The advantage of these agents are going to be that they are oral. If the phase 3 data comes to fruition, they may be somewhat safer regarding infections than tofacitinib has been, but this, again, remains to be determined. Lastly, sphingosine-1-phosphate inhibition has already been demonstrated to be effective in other inflammatory conditions, such as multiple sclerosis.

There are several S1P agents that are finishing phase 3 trials, including ozanimod, which has a very promising both efficacy and safety profile that should allow another oral agent for moderate-to-severe ulcerative colitis in addition to the agents that we have.

Now, clearly, comparative-effectiveness studies are going to be needed. Unfortunately, none of these have had exceptionally better results than our current therapies. We're still handling the 30% to 50% remission rates, even with the newer treatments.

We continue to need to evolve our therapies and improve them, which might include combining different mechanisms of action, looking outside pharmaceuticals, including changes in the microbiome, and of course, dietary manipulation as a prebiotic may have benefits as well.

Not only do we need to look at agents 1-on-1 and compare them to each other, but we need to be expanding our repertoire by combining mechanisms of action in the future, and of course, trying to improve our efficacy while maintaining our good safety profiles.

The crystal ball is not entirely clear. I anticipate some evolutionary progress over the next several years, but revolutions are still a ways away for the treatment of both ulcerative colitis and Crohn's disease.