Examining the Long-term Clinical Evidence of Therapies for Inflammatory Bowel Disease in Bio-naïve Patients - Episode 9

Second-Line Therapies for CD

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Miguel Regueiro, MD, offers his clinical advice on second-line therapies for patients with Crohn’s Disease (CD).


David Hudesman, MD: Miguel, we’ll take your moderate-to-severe patient—more on the moderate end—with luminal disease on a first-line therapy who loses response. We check the objective markers, and we’re confident this is active disease. What do you think about second line? Do you have the same options: TNF [tumor necrosis factor], vedolizumab, IL-12/23, IL-23? Or do you think about things differently?

Miguel Regueiro, MD: There’s a bit of a distinguisher. Let’s also make sure we don’t give up on that first 1 before we’re fully optimized. Let’s assume we’ve changed the dose, duration, and interval. Whether or not it’s a TNF, we’ve checked levels. Assuming all that, and they’re truly not responding, we optimize that first. We burn through our biologics too fast if we don’t do that. We’ve all probably had referrals when a patient has been on 3 or 4 biologics, but they probably just needed to optimize the first or the second. Coming back to your question, this is where vedolizumab is a distinguisher, in that vedolizumab as a second-line agent is inferior. All the studies have shown, especially behind the TNF but probably behind an IL-12 and an IL-23, that vedolizumab isn’t as effective. If vedolizumab isn’t the first-line agent, then I won’t use vedolizumab as the second-line agent. If vedolizumab is the first line, then we’re looking to switch to something else.

Then it gets into what they’re on to begin with and how quickly we need them to improve. If they’ve been on an anti-TNF, I’ll go to an IL-12/23 like ustekinumab or an IL-23 like risankizumab. If they’ve been on 1 of the IL-12/23 or IL-23, then you have some options. Can you switch within class? Is there any benefit in that? We’re seeing some data with ustekinumab followed by risankizumab. We don’t have enough with risankizumab followed by ustekinumab, but you may get a 35% to 40% pickup.

However, we have to be careful because we have to get it right. We don’t also switch within class. If a patient goes through 6 more months, have they gone back on steroids? They’re failing. Usually I’ll switch out of class, especially if they’re more severe. If it’s an IL-12/23 or an IL-23, I’m going to TNF inhibitors next. If it’s a TNF inhibitor first, then it’s the IL-12/23 or IL-23. The nice thing is we have options. For Crohn disease we have infliximab, adalimumab, and certolizumab. That’s how I look at it. If it’s been a TNF, and they develop very bad psoriasis, it’s easy. Psoriasiform reactions with TNF and even the IL-23, specifically risankizumab, may even give you a little more of a bump. If insurance approves ustekinumab, I’d use that as well.

Transcript edited for clarity.