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IBD Treatment: Translating Data Into Clinical Practice
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Miguel Regueiro, MD: The 1 point I wanted to bring up, Jean-Fred, is this: you mentioned this new HEMI [histo-endoscopic mucosal improvement]. This was in the UNIFI study, in which we looked at ustekinumab. As you said, this is a more rigorous pairing of endoscopy and histology. The FDA—from the sense I’m getting, and obviously you’ve been involved in this as well—will probably use that at least for UC [ulcerative colitis] We’ll probably use that or a version of that going forward, so it’s an even more rigorous objective end point, which is interesting.
The 1 point I always make is this: Don’t let perfect be the enemy of good. In clinical practice, you may have a patient who has gone from severe Mayo 3 to Mayo 1 [Disease Activity Index] with some inflammation, but they’re much better. I would certainly not switch them to another biologic because they still have histologic or even a bit of endoscopic inflammation, but it’s an interesting new end point.
Jean-Frederic Colombel, MD: Miguel, I completely agree with you. The point is that we still don’t know if it’s beneficial for the long-term progression that Doug was talking about. Will we stop the progression of UC by switching from clinical or endoscopic remission to mucous healing? We don’t know. We have and we have these ongoing prospective studies that may answer us, but it will take several years. I completely agree with you. We need to be cautious because as we say in French, Le mieux est l’ennemi du bien (“Perfect is the enemy of the good”).
Miguel Regueiro, MD: I don’t know if you just offended me.
Jean-Frederic Colombel, MD: The best is the enemy of the good sometimes, so I completely agree. When you have a drug that is working, and the patient is doing well, you still scope. It may be a complex patient with UC. It’s not Mayo 0 but 1, and you still have some neutrophils and biopsies, so it’s not perfect, not histologic remission. I don’t think it’s enough to switch. It may be to optimize, so we need to be very cautious. In clinical practice, you know that as well as I do because you have so much experience, Doug and Miguel. All patients differ. It depends on what other drugs they have been exposed to in the past, right?
Miguel Regueiro, MD: Yes, and it’s interesting when we talk about when we switch from 1 agent to the other. I also want to bring up the quality-of-life scores that came up in the UNIFI study with ustekinumab, which talks about histology. Before I get to that, Doug, I know you had a comment too. When do we switch from 1 agent to another?
All of us agree that, for mild symptoms when they’ve been severe and mild inflammation when they’ve been severe, it is probably not enough to switch. The way I look at it is this: If they have a reaction to the drug or an adverse event with the drug—and we can define that broadly: if they’ve truly been optimized on the drug, and we know this from anti–TNF [tumor necrosis factor], and if we check levels and we see what we’d like therapeutically, with no antibodies and we really push the intervals and we push the dose—that’s when we switch.
I completely agree with you, Jean-Fred. The knee-jerk reaction sometimes is to switch too soon, and then we’re burning through these biologics, and we have to be careful for that. Doug, I’ll let you make a comment, but then maybe you could follow it up by talking about quality of life with ustekinumab in the study.
Douglas C. Wolf, MD: Quality of life is the most important measure in many ways in our clinical trials, though it’s always a secondary end point rather than a primary end point. Five or 10 years ago, we were talking to the FDA and said we should maybe make it a primary end point, but they weren’t interested.They want mucosal healing, which is very important of course, but for patients and for us, caring for the well-being of our patients’ quality of life is immensely important, and it is an equal partner to mucosal healing.
The ustekinumab studies demonstrated consistent improvement in quality-of-life measures with induction and maintenance of ustekinumab therapy vs placebo that there were improvements that were sustained. The metrics measured in quality of life are how you feel, how you feel about yourself, how you feel about others, and how you feel at work. There is also the WPAI [Work Productivity and Activity Impairment], which is a work-productive measurement, and that’s also something that is improved. There are all sorts of measures that are additional measures of how these medications are working that truly make a difference in people’s lives. Ustekinumab hits all the marks.
Miguel Regueiro, MD: Great. Not only is there histo-endoscopic mucosal improvement, but it improves quality of life as well.
Transcript Edited for Clarity
