Plaque Psoriasis: Placebo Controlled and H2H Studies

Mark Lebwohl, MD: In reviewing the VOYAGE 1 and VOYAGE 2 trials of guselkumab for psoriasis, this is an IL-23 [interleukin-23] blocker. It is dramatically effective for psoriasis, and it beats placebo, of course, by a lot. But it also beats adalimumab by a lot. It’s a very effective treatment, and that came through loud and clear in the trials. As you look at the results of the trial, it gradually improves psoriasis but continues to improve it up through week 16. That benefit persists for a long time thereafter.

In the UltIMMa-1 and UltIMMa-2 trials, risankizumab was compared to ustekinumab, 1 of the most effective treatments we had over the past decade, and to placebo. Risankizumab was dramatically more effective than placebo and also significantly more effective than ustekinumab. Here again, it’s an IL-23 blocker that beats all of the comparators and reaches levels of improvement that we didn’t have before this.

The reSURFACE 1 and 2 studies looked at the comparison between tildrakizumab, a new IL-23 blocker, to etanercept and to placebo. There were 2 doses of tildrakizumab that were studied. Both were superior substantially to placebo and to etanercept. In this study, in contrast to the other IL-23 studies, they probably picked too early an endpoint because as you look at the studies, what you see happens is the patients treated with tildrakizumab continued to improve beyond week 12. Actually, even beyond week 16, those patients continued to get better.

But the primary endpoint that was selected was week 12. That was probably an error, and it may have been an error because Merck & Co, the company that ran the trials originally, did not have experience in psoriasis. They selected week 12, which was an old endpoint for old therapies that worked perhaps more quickly but at a time when initial studies were only being done for 12 weeks. Nowadays, most of the drugs we test actually look out to 16 weeks. Tildrakizumab’s package insert suffers from that. Had they looked 4 weeks later, they would have done a lot better. But in the reSURFACE 1 and 2 trials, still the drug is dramatically more effective than placebo and then etanercept. It actually continues to work in subsequent trials for years.

I have quite a number of patients on tildrakizumab, and they are uniformly happy. I’ve had almost no patients, I think only 1 patient actually, stop using tildrakizumab of many that I have on the drug, for lack of efficacy. The drug not only works well but continues to work. One of the benefits it has, as do the other IL-23s, is it’s not given often. It’s given 4 times a year, and so this is a drug that makes patients’ lives as close to normal as possible. With only 4 shots a year, you basically go about your business the rest of your life. You don’t have to give yourself injections every week, or every 2 weeks, or every month, and you don’t even have to give yourself injections. They’re administered in the doctor’s office 4 times a year. That is a big advantage of this therapy over others.

One of the advantages of using IL-23 blockers that are administered in the office has over other treatments is an insurance advantage, particularly patients on Medicare where we can’t use various companies’ free drug programs, discounts, or coupons. Patients have to pay whatever the co-pay is. If the drug is administered through a pharmacy benefit, patients have to pay that pharmacy benefit. If they have Medicare Part D, there’s a donut hole which is usually a few thousand dollars, at least $5000. Patients have to pay that every year. Whereas if they get a drug that’s administered in the doctor’s office, it’s part of their medical benefit so that they don’t have to pay anything. It’s administered in the doctor’s office, as long as they have coinsurance that covers all of their visit.

With many of the drugs that we use in patients who are obese, which is part of the metabolic syndrome, the drugs simply don’t work as well. We see that over and over again with most of the drugs that we use, actually. The data from the tildrakizumab study show a very minor impact of weight on the response to therapy. Specifically in patients with or without metabolic syndrome, they still respond very well to tildrakizumab.

Transcript edited for clarity.