Gil Y. Melmed, MD, on Positioning Therapies in IBD

Dr Melmed previews the panel session on positioning therapies in IBD that he will chair at the Advances in Inflammatory Bowel Diseases 2021 regional meeting April 16. Joining him on the panel will be Uma Mahadevan, MD, from the University of California San Francisco; William Sandborn, MD, from the University of California San Diego; and Michael Chiorean, MD, from Virginia Mason Medical Center in Seattle.

Gil Y. Melmed, MD, is codirector of Clinical IBD at Cedars-Sinai in Los Angeles, California.

TRANSCRIPT:

Dr. Gil Melmed:  I'm Dr. Gil Melmed at Cedars-Sinai Medical Center, and it is my pleasure and privilege to be chairing the AIBD, the Advances in IBD Regionals Event in Los Angeles on April 16th.

I will have the privilege of moderating a session on positioning of therapies together with my speaker panel, Dr. Bill Sandborn, Dr. Uma Mahadevan, and Dr. Michael Chiorean from Seattle, and excited to be thinking about and talking about some of our newest therapies which are either recently approved or will be hopefully approved in the near future in the context of our existing therapies.

Really, trying to make sense of, which therapies do we use? When do we use them? How do we think about positioning one relative to the other? In order to really best address this question, we should have head-to-head trials where we can compare drug A directly to drug B in the setting of a randomized clinical trial.

It's difficult to be able to do that for all of these different combinations of therapies and expensive. It takes time. Right now, at least on our landscape, we have one head-to-head clinical trial in ulcerative colitis that positioned adalimumab versus vedolizumab.

We don't have very much in the way of these head-to-head clinical trials. We do have sophisticated ways of analyzing existing data in the form of network meta-analyses that have suggested which drugs perhaps we should be using first line for both Crohn's disease and ulcerative colitis in the form of anti-TNF like adalimumab for Crohn's disease, vedolizumab or infliximab for ulcerative colitis.

But also, having some newer therapies which may or may not have been part of those network meta-analyses where they really try to line up the drug effect versus a placebo effect and then compare drugs based on how the placebo responses may relate to each other.

With these sophisticated ways of analyzing pre-existing data, we still don't have the level of rigor that we would be able to get from head-to-head clinical trial. Fortunately, the efficacy for most of these agents seems to be fairly similar across the board.

There isn't an obvious standout in terms of efficacy that we've seen in Crohn's disease. At the same time, we also are looking at the safety aspects of these medications as well to help us understand the positioning of how we should be positioning one drug relative to another.

When it comes to efficacy, as I've mentioned, we have a head-to-head trial of adalimumab versus vedolizumab in ulcerative colitis where vedolizumab seemed to outperform from an efficacy standpoint. We do have network meta-analyses, which suggest the superiority from an efficacy standpoint again for some drugs relative to others.

Then we have the safety side of things. From the safety side of things, we are looking at potential class effects of medications, for example, anti-TNF that have been associated with certain adverse events that are not associated with other classes of drugs, for example, lymphoma that has been seen in anti-TNF that has not been seen in ustekinumab or vedolizumab.

That being said, we also need to recognize that the likelihood of these adverse events are very, very, very low. Overall, thinking about an individual patient that may be in front of us, how do we think about positioning of this patient?

These are questions that we'll be posing to our panel and really using some of the data to guide decision-making, thinking about individual patient profiles in terms of their tolerance for risk in terms of their severity of disease, and understanding what might be the most acceptable balance of efficacy and safety for any given patient.

Finally, we'll be also briefly touching upon some new tools that can be available to help guide how to optimally think about choosing a medication for a given patient by inputting some basic patient characteristics that may help also guide the conversations with patients taking into account patient preferences and taking into account specific patient profiles in order to optimally position one therapy against another.