Scott Gottlieb, MD: We’ll put the TNF [tumor necrosis factor] inhibitors aside because we know that TNF is important in forming and maintaining granuloma, so that if you block TNF it certainly makes pathological sense that you should develop disseminated TB [tuberculosis]. And yet we have all these other classes of drugs that we don’t think really have any sort of pathogenic mechanism that would relate to TB. And in fact, it was with one of the IL-23 [interleukin-23] inhibitors that in one of their clinical trials they allowed patients who had latent TB not to get prophylaxis with drug and still maintain in the trial, and none of them developed disseminated TB. It’s clearly off-label. It’s clearly in the label that we need to be at least checking for TB.
Mark Lebwohl, MD: Right. That’s actually true of all of the IL-23s. And in fact, IL-17 does play a role in granuloma formation, but there’s an experiment done where they implanted mycobacterium tuberculosis [MTB] in the lungs of mice, and then knocked out the cells that make IL-17—essentially giving them IL-17 blockers or IL-23 blockers, which also would knock out IL-17—and there was no progression of the MTB. So at least there are some animal data to support it, and certainly in clinical trials for the IL-17s and for the IL-23s, we are not seeing reactivation of latent tuberculosis.
Brad Glick, DO, MPH: Maybe where TB is concerned, it’s that upstream IL-23 blockade, a little bit different than more downstream interleukin-17 blockade, because you’re down regulating TNF as well when you’re decreasing interleukin-17.
George Han, MD, PhD: I want to echo for tildrakizumab, the safety data are excellent. That stands out to me for that medication certainly. And I think efficacy-wise, we’re in the state where we’re used to really high numbers, I would keep in mind that the median improvement in PASI [Psoriasis Area and Severity Index] for a patient on tildrakizumab is 96%.
Scott Gottlieb, MD: I would say when I look at the package insert or when I look at the data on tildrakizumab, I think the most important part of that safety information is what’s not in there. Lots of injection site reactions. There were no new cases of onset IBD [inflammatory bowel disease]. I don’t believe that there were any MACE [major adverse cardiac events], or it certainly was similar to placebo. Infections were low. Injection site reactions were low. I think what’s not in the safety information is probably the most important part of that safety information in a good way.
Brad Glick, DO, MPH: And I think about weight too. This is a drug that I think actually performs well, perhaps even at some of the higher weights, and that’s been my experience in patients on tildrakizumab as well.
Mark Lebwohl, MD: Data support that. We’re actually going to talk about that in a minute. But I will say, from your comment, Scott, one of the real standouts was they picked week 12 as their endpoint. And anyone would have looked at those data and said, “At least go to week 16.” In fact, if you look at their data, the drug peaks at week 22. So it’s very slow to get there but it does; it does very well at week 12, but it does much better at week 22.
Scott Gottlieb, MD: Which is why you can’t ever compare topline data from 1 drug to another. They have to be head-to-head trials, and I think that’s a great example of that. Now I’ll ask you a question. I was in the trial, I did the reSURFACE trials as well. I think my last patient just finished the trial. I’ve certainly had patients on that drug for 5 years. So it’s relatively new to the market, but it’s really not new. I think the transition from Merck to Sun Pharma got it caught up a little bit in terms of coming to the market, but I’ve probably had patients on that for almost 6 years now.
Mark Lebwohl, MD: We actually have a large number of patients on tildrakizumab. And I will say, unlike any other drug, we’ve had 1 dropout out of a large number. And that was for lack of efficacy.
Brad Glick, DO, MPH: It’s pretty uncommon.
Mark Lebwohl, MD: Literally everybody else we have is quite happy with it. And the data now are going up beyond 3 years where the durability of response simply clearly lasts. The other important thing that you said, which you said very quickly but I’m going to repeat it, is it’s the 1 drug that you have to give in the office. And when I have a Medicare patient and they have Medicare Part D, there’s that $5000 donut hole. You want to prescribe a different drug for them, and then you tell them, “Well look, it’s going to cost you $5000.” And by the way, when they call Medicare, they don’t tell them it’s just $5000, they say it’s $1800 a month.
The patient then does the math. They multiply by 12, and they think, “I can’t afford this.” I explain to the patient that it’s just $5000 and then 5% of the cost of the drug. So maybe it’ll come to $7000 or $8000 or $9000 for the year, and that’s for all their drugs, but the patients will not do it. So for Medicare patients it’s almost a knee-jerk response, “I’m going to an IL-23 blocker that can be given in the office,” because it saves them a lot of money. And that is a huge source of my IL-23 patients. So, other comments about tildrakizumab?
George Han, MD, PhD: I think it actually should have been, as you mentioned, the first foray into the IL-23 space. I think perhaps some of the other agents in the class have benefited from the trial design and saw that week 12 wasn’t the way to go. But certainly, I think in terms of long-term efficacy, durability, safety, it’s a great medication. For patients, we’ll I think talk about comorbidities and other factors to think about, but when you start to look at the relapse data, you start to talk about patients who even after stopping the drug keep their clearance out to half a year or more after the last injection. I think that’s really important, especially for some of our patients or women of childbearing age. We have a couple of strategies to deal with them, but I think by and large in terms of that class effect, IL-23 has a good lasting efficacy, and we do see that with tildrakizumab.
Scott Gottlieb, MD: Which I think is an extremely important statement from a clinical standpoint, because we were just talking about live vaccines and if you really need to stop them, and that we do because that’s what’s in the label. But using those recapture data where patients are off the drug and then restart the drug, they often do well off the drug for weeks if not months, and then they do just as well when they go back on. I think that’s very important clinically because it makes me very confident that I could be conservative in my recommendations and say, “Sure, stay off this drug, get your surgery done, or get your live vaccine,” because I know they’ll do well for weeks if not months off the drug, and they’ll do just as well when they restart it. I think those recapture data, for me, clinically, are very relevant, so thanks for bringing that up.
Brad Glick, DO, MPH: I would also add in that there are some cardiometabolic factors that were also evaluated in a post-hoc analysis for reSURFACE 1 and reSURFACE 2.
Mark Lebwohl, MD: Why don’t we talk about those and then we’ll talk about the other drugs.
Brad Glick, DO, MPH: Right.
Mark Lebwohl, MD: Because that was striking.
Brad Glick, DO, MPH: I think so too. And while I don’t believe that there were statistically significant differences, there were some numeric benefits: decreases in blood pressure, components of the metabolic syndrome, decreases in systolic blood pressure, fasting blood sugar, and then also triglycerides. And I think that’s important. It’s another discussion, which is very similar to some degree to the TNF story and managing our comorbidities. I think more needs to be done, of course, clearly. But I think that those are very important factoids.
Mark Lebwohl, MD: I would say that it’s fascinating to me that those decreases occurred with the approved dose, the 100 mg dose. With the 200 mg dose they didn’t. But I agree with you, that’s interesting. You also said earlier something that was very clear. There’s very little loss of response with obesity with tildrakizumab. And we’ll talk about the other IL-23 blockers too, but with tildrakizumab specifically there were very similar responses in obese patients as in nonobese patients.
Transcript edited for clarity.