Plaque Psoriasis: Design and Endpoints of the reSURFACE Trials

Mark Lebwohl, MD: Why don’t we get to the data on the IL-22 [interleukin-22] blockers, for which there are a ton of data? Who wants to tell us about the reSURFACE data with tildrakizumab?

Scott Gottlieb, MD: I can. There were 2 trials done, reSURFACE 1 and reSURFACE 2. Basically 1-year trials. The primary endpoint occurred at week 12, and that was PASI [Psoriasis Area and Severity Index] 75. The dosing, of course, is 100 mg at weeks 0, 4, and every 12 weeks thereafter. The actual clinical trials had a more robust study design with other dosing schedules. But the FDA-approved dose is weeks 0, 4, and every 12 weeks thereafter.

And all primary endpoints were met, so roughly around two-thirds of patients achieved a PASI 75 at week 12. But what’s interesting about tildrakizumab, and I think is important for people to understand, is that it’s an example of a drug where the primary endpoint is by far not where you see maximum efficacy.

So they got dosed at week 0 and 4 and came back week 12 for their primary endpoint evaluation. Then they got a third dose at week 16. They came back at week 28 for a secondary evaluation, and they did much better than at week 12. So by week 16, PASI 75 was around 75%, which is how I gestalt it in my mind.

The same thing was true of PASI 90. About a third of patients did well, achieved PASI 90 at week 12. But with that third dose, that went up to close to half of the patients. And similarly, PASI 100 had a modest response at week 12, but a much more robust response later. About a quarter of the patients or so achieved PASI 100 at week 28.

Furthermore, in that study, if you are a PASI 75 responder at week 28, then you were able to go into the extension trial, and those patients who continued on the drug did well. About 85% of patients who were PASI 75 responders at week 28 maintained PASI 75 out to week 52 or 64.

In addition, there are some long-term data showing that if you stayed on the drug out to 3 years, you’ve maintained efficacy. So I think we have nice efficacy data showing that it works. It may not be the quickest one out of the block, but that’s not my goal. My goal is to win the race, or at least do as good as anybody else in the marathon. I’m not a 100-yard dash kind of guy. And my patients aren’t either. They want to get better quicker. But as long as they see a steady improvement, they’re willing to wait. The nice thing about the drug is that you could tell very early on, by week 4, certainly by week 8, if your patient will do well long term. If your patient has a modest response, maybe PASI 40 or less at week 8, they’re probably not going to be good long-term responders. But if they have a more robust response, maybe PASI 50 or 60 at week 8, you could tell that they will be a good long-term responder.

In my clinical practice I give a dose at week 0, I give a dose at week 4, and then I might see them back at week 8, or 12, or whatever, even before their third dose. And if they’re not doing well, I stop and I go to something else. But if they are doing well, even if they haven’t achieved a PASI 75 or a significant improvement at that point, I know that they will by week 28. And then the nice thing is that if they do respond by week 28, then I know that they’ll continue to respond out to a year and possibly to 3 years.

I think the safety profile of IL-23 as a class, and I would include tildrakizumab certainly among these; I don’t see that, there’s virtually no signal. There are certainly things that are important in the…package insert, but I think that they are very reasonable. It mentions infection, it mentions TB [tuberculosis], although there were no cases of reactivation of TB and there were several dozen patients with latent TB in that clinical trial. It mentions not giving live vaccines. I don’t know, Mark, maybe you could back me up on this, but has there ever been a patient who’s been given a live vaccine who’s developed a disease state for which they were given the vaccine?

Mark Lebwohl, MD: No. The best study on that was done for TNF [tumor necrosis factor] blockers, which are actually substantially more immunosuppressive. It was published in JAMA, and they divided the patients into 2 groups, patients on TNF blockers who got a live vaccine and patients not on TNF blockers who got a live vaccine. There were no more cases of the vaccine not working. The frequency of herpes zoster, which was the vaccine that was used, was no higher in the patients on TNF blockers. So the vaccine worked well, and there were no cases of disseminated zoster.

And so everything we were worried about did not happen. Nonetheless, the package insert does make the statement about live vaccines. I know that when we send our patients to infectious disease experts, they respect that. They actually are very wary about giving live vaccines to patients on any of the biologics. But I would agree with you that it is not evidence-based.

Transcript edited for clarity.