In this video, Dr Ananthakrishnan discusses his presentation about the Clinical Year in Review from the 2022 Crohn's and Colitis Congress, on important research published and its implications for IBD care.

Ashwin Ananthakrishnan, MD, is director of the Crohn’s and Colitis Center at Massachusetts General Hospital and Associate Professor at Harvard Medical School.

TRANSCRIPT:

Dr. Ashwin Ananthakrishnan, MD, MPH: Hi. I'm Dr. Ashwin Ananthakrishnan. I'm an Associate Professor of Medicine at Massachusetts General Hospital. I presented on the clinical year in review at the Crohn's & Colitis Congress held virtually in January 2022.

Over the course of this presentation, we highlighted some of the key studies that were published in the scientific literature in the IBD space over the past year and discussed how they may impact our practice.

One of the first topics that we covered in this clinical year in review was data about new drugs that are available or will likely be available later this year for treatment of either ulcerative colitis or Crohn disease.

Ozanimod is a sphingosine-1-phosphate receptor modulator, where the Phase 3 trial was published in the "New England Journal of Medicine" earlier this year.

In the induction and maintenance studies, ozanimod at a dose of 1 milligram per day in the induction study and 1 milligram per day for 52 weeks in the maintenance study showed significant improvement in attaining clinical remission or endoscopic improvement compared to placebo.

There were no major safety concerns with this new mechanism of action. The side effects included infections and a slight increase in risk of bradycardia and atrioventricular conduction delays.

We also reviewed two other drugs that were distinct therapeutic mechanisms that showed very promising results in Phase 3 trials.

Upadacitinib is a JAK-1 preferential inhibitor. This year, we saw the publication of Phase 3 randomized controlled trials on both induction and maintenance compared to placebo.

The induction trials showed that 45 milligrams per day of upadacitinib was substantially better than placebo in achieving both clinical remission and endoscopic improvement but very high rates of both these outcomes.

In the maintenance phases, both the 15 milligrams a day and the 30 milligrams a day dose over 1 year were significantly better than the placebo, suggesting, again, that this is a very promising and new mechanism of action.

A third drug that is likely to become available later this year, but this time was for Crohn disease, was risankizumab. This is an IgG1 monoclonal antibody that targets the p19 subunit of interleukin-23.

Just as a reminder, a currently available treatment, ustekinumab, targets something that is called the p40 subunit that is common to both interleukin-23 and interleukin-12. This is a slightly more targeted anti-cytokine.

What it showed in the Phase 3 randomized control trials was that when administered intravenously at week 0, 4, and 8, risankizumab was significantly better than placebo in achieving clinical remission and in endoscopic remission.

When administered subcutaneously for up to 52 weeks, it was more effective than placebo in attaining these outcomes over one year, again supporting an important addition to what we have currently to treat Crohn disease and ulcerative colitis.

We saw two important comparative effectiveness trials. We are seeing more of this in the Crohn disease and ulcerative colitis space, and that is very important because as we have more drugs available, we also need to understand how they position with respect to each other.

We had the SEAVUE trial presented in the Crohn's & Colitis Congress and at other meetings where it's compared ustekinumab to adalimumab in biologic naive, moderate to severe Crohn disease. This trial very promisingly showed that both drugs were similarly able to achieve clinical remission and endoscopic remission at week 16 and at later time points.

In addition to new drugs, we had new therapeutic targets that were prescribed by expert groups. The International Organization for the Study of IBD (IOIBD) very nicely outlined in their STRIDE-II consensus statement what our goals are for treatment of Crohn disease and ulcerative colitis, emphasizing again that while symptomatic response is still an important first target. We are moving beyond this to emphasize the importance of normalization of inflammatory markers such as CRP and calprotectin and achieving endoscopic healing in both Crohn disease and ulcerative colitis.

There are additional treatment targets such as histologic healing and transmural healing that are not yet part of standard of care but are very actively being investigated in clinical trials to understand where they fit into our treatment algorithm.

The last set of data that I want to go over with you is data on the COVID vaccine antibody response. Clearly, this has been a very important topic over the past year or two. We now have a number of different studies conducted in many different settings, in Israel, in the United States, in the UK, that have looked at how immunosuppression impacts response to COVID-19 vaccines.

Very reassuringly, all these studies showed that when patients received a 2-dose vaccine, either the mRNA vaccine or the other vaccine types, they had very high rates of antibody response that were not significantly impacted by their immunosuppression.

This also translated into clinical protection, in that it resulted in very few patients developing infections, similar to that seen in the general population as well. Again, reassuring our patients that being on immunosuppression at the time of their COVID vaccine does not significantly hamper protection from the vaccine.

And that were some of the key studies that we looked at in this year's clinical year in review. Thank you.