Case Based Expert Perspective on the Management of Generalized Pustular Psoriasis - Episode 5

Case 2: Changing the Treatment Paradigm

Mark G. Lebwohl, MD, comments on the clinical implications of the recent approval of spesolimab for the treatment of generalized pustular psoriasis.

Mark G. Lebwohl, MD: This is an ill patient. The patient could have kidney damage, so we’re going to have to be on the lookout for that. The patient has active disease and needs a treatment that will work as quickly as possible. Spesolimab, a monoclonal antibody that inhibits IL-36, was recently approved as an intravenous injection for the treatment of patients with generalized pustular psoriasis [GPP]. What makes the mechanism of action and clinical profile of spesolimab unique? How does it differ from existing treatment options for GPP?

First, this is the only approved treatment for generalized pustular psoriasis in the United States. Second, what’s unique about the mechanism of action is that there’s a group of patients born with the deficiency of the IL-36 receptor antagonist, a syndrome called DITRA. Those patients have a clear mechanism explaining why IL-36 is in the pathway for the development of psoriasis. By blocking IL-36 or its receptor with drugs like spesolimab, that opens an opportunity to save patients quickly. In fact, in the phase 1 study, the majority of patients treated with a single infusion of spesolimab cleared quickly. By day 8, most were cleared. A second infusion was given at day 8, and patients even further clearing among the patients in the trial, so that’s a dramatically effective treatment. In the phase 2 study, the proportion of patients who had a pustule score of 0 was over 50%—I think it was 54%. With the second infusion, which was open label, even more patients cleared. Spesolimab is a major breakthrough in the treatment of pustular psoriasis.

What about other treatments that are available? In Japan, there are a number of approved treatments. The end points in Japan tell you how important it is for us to have a new drug. The end point that was considered a treatment success was any improvement at all in generalized pustular psoriasis. If the patient improved even a little, that was considered a treatment success and was the basis for approval of these drugs. Fortunately, spesolimab clears patients. The majority have no pustules left at 1 week.

The other flaw in some of the other drugs that are used for pustular psoriasis is that PASI [Psoriasis Area and Severity Index] scoring is used in the majority of studies, but PASI scores aren’t great for pustular psoriasis. What we worry about is pustules and inflamed skin. The skin isn’t thickened. Duration, which is 1 of the components of the PASI score, doesn’t apply. It’s important that we use scores that look at, for example, numbers of pustules or a generalized special psoriasis global assessment score. If we do those, we’re likely to come up with better treatments GPP.

I’m often asked the question, what patients would you consider for this treatment? Until now, I say that unless the patient has a contraindication, if they have GPP, they should get spesolimab. It’s the most rapidly acting treatment, and it works right away. In the United States, it’s the only approved treatment. For that reason, I would use it. Until now, what treatments did we use? Because the disease can be severe and so dangerous, we always go for the treatment we think is going to work best. The treatments that are the fastest for plaque psoriasis are generally cyclosporine and IL-17 blockers. We often will turn to those. Retinoids are unpredictable. They can work extremely well and quickly or not work at all. For these patients, we used to start them on retinoids and even cyclosporine, which has a lot of adverse effects but would help patients clear more quickly. How often do I anticipate this treatment will impact quality of life and disease outcomes? Most patients will benefit from spesolimab, and it will improve the quality of life for most patients.

Transcript edited for clarity