Miguel Regueiro, MD: Jessica, when you look at therapeutic outcomes, first for anti-TNF [tumor necrosis factor], what's the expected response? Even just practically, what do you tell your patient in the clinic about therapeutic outcomes with anti-TNFs? Then, I want to touch on ustekinumab, especially some of the data in quality of life, and I’ll ask Bill for some of his input on those as well. What are your outcomes for anti-TNFs? When you start somebody, what do you look for? You mentioned before, but get into that a little bit now.
Jessica R. Allegretti, MD, MPH: When I'm discussing it with a patient and we're making a decision about which therapy to start, if we're starting with an anti-TNF, I will use infliximab as an example here. One of the things we've been alluding to is the speed of action of that medication. I discuss with patients, especially if this is their first biologic, we expect that by the end of induction, we want them to be feeling better. If you look at the original clinical trials, ACT-1 and ACT-2, about 64% of patients had a clinical response by the end of induction, and about 35% of patients were in remission. I'm following patients closely around that week-14 mark to see if we are hitting some of those targets, and then making adjustments if need be because you may need to optimize your dose, dose escalate.
I also always talk to my patients up front, before I start any therapy. When we're going through risks and benefits, I say one of the biggest risks is that this drug is not going to work for you. We have to prepare for that and be on top of that, so if you are a primary nonresponder, for example, we move on quickly, and we don't delay getting you on appropriate therapies. I discuss that up front as well.
Miguel Regueiro, MD: Bill, ustekinumab is the newest biologic or monoclonal antibody that we have for Crohn disease, and then in a minute, I'm going to ask David about UC [ulcerative colitis]. Tell me a little bit about vedolizumab and ustekinumab for Crohn disease, also with some of the data on quality of life.
William J. Sandborn, MD: In terms of the active disease, you’ve got 2 groups of patients. You have patients who are naïve to TNF blockers, and the data that Jessica was just talking about applies to anti-TNF naïve patients. You would expect about a 60% response rate by clinical measures in naïve patients. It's lower if you're having your second anti-TNF. For ustekinumab, when the clinical trials were performed in Crohn disease, there were 2 different patient populations that were studied in separate clinical trials. In the anti-TNF naïve patients, the response in Crohn disease was also about 60%, so very similar to what you would expect to see with infliximab or adalimumab. What differentiates it in my mind is that you don't have black box warnings. You have the large intravenous load that you like with infliximab, and then you have every-8-week subcutaneous dosing for maintenance, which is like adalimumab but much less frequent. That all fits together nicely and impacts adherence, compliance, and patient acceptance. It's part of the spectrum of quality of life.
For vedolizumab, the effects in anti-TNF experienced patients were less profound. In fact, in the pivotal clinical trials, there were several trials that looked at it in subgroups of patients at anti-TNF failure and didn't see a significant induction effect. As you get into the maintenance, you can eventually see a benefit for vedolizumab. In the failure patients, it’s not quite as potent. It's quite safe, and there will be patients for whom it works. The ustekinumab effect is probably stronger.
In the naïve group, there are patients who will respond to vedolizumab. There's a clinical prediction tool that helps pick those out. There's an evolving clinical prediction tool for who's going to respond to ustekinumab as well. These clinical prediction tools will have a larger role in our practice in the years to come, but even without selected patients, you get a good effect in naïve patients. Then, in the failure patients, you see a nice effect as well with ustekinumab for induction and maintenance.
The quality of life tracks heavily with clinical response and remissions. You get the most bang for the buck in the response. When you take moderate-to-severe Crohn disease or ulcerative colitis, they have terrible quality of life if you put it in a generic, health-related quality of life assessment, like SF-36 [Short-Form 36 Health Survey]. It looks like class 3 or 4 congestive heart failure or chronic renal failure with hemodialysis. It's shockingly bad. Then when you get a response, you get up to just below population means for health-related quality of life, so you get most of the rise with the response. Then if you get into remission, amazingly, the health-related quality of life exceeds the population means around the world. Quality of life heavily tracks to having clinical improvement or response.
Miguel Regueiro, MD: You alluded to, both you and Jessica, that Bruce Sands, [MD,] study in 2018 that looked at ustekinumab and improvements in quality of life. As we talked about earlier, the quality of life impact in IBD [inflammatory bowel disease], that class 3/4 heart failure, these are some cases of very poor quality of life. It's interesting how we look at treat-to-target, but we also take into account the quality of life.
Transcript Edited for Clarity