DISCOVER-1/2 Trials in PsA

Transcript:

Anthony M. Turkiewicz, MD: We’ve talked about some of the classes. Let’s take a deeper dive into interleukin-23 inhibitors. For us in rheumatology, this approval has occurred over the past several months. Dermatology has had it for years. John, I’ll start with you. Guselkumab is the first approved among the IL-23 inhibitors for treatment of adults with severely active PsA [psoriatic arthritis]. Can you go over the study design of DISCOVER-1 and DISCOVER-2, the pivotal phase 3 trials and the clinical trial program for PsA? Perhaps discuss some key outcomes and the patient population in those 2 studies.

John Tesser, MD: This is an interesting class, the anti–IL-23 class. In my brief discussion about the pathophysiology of the disease, I tried to point out how important this cytokine is. We think of it as upstream from IL-17. What’s interesting in the history of IL-23 in terms of our treatments is the IL-12/23 ustekinumab, which has pretty good skin effect and not very good joint effect. It never was used often in treatment of psoriatic arthritis, but it’s quite good in colitis. With IL-23 alone, where the P19 subunit is hit by the monoclonal antibody, we’re seeing a differential effect.

There were 2 phase 3 studies that led to the approval of this drug by the FDA. Dr Philip Mease was the first author on the publication of DISCOVER-1, which was a combination population in which they allowed patients who had been on 1 to 2 TNF [tumor necrosis factor] inhibitors to go into the trial. About a third of the patients were TNFexperienced for this study. For Dr Atul Deodhar’s paper, which came out in 2020, both publications are in the Lancet, this DISCOVER-2 trial was a pure TNF biologic-naїve population.

There were about 400 patients in these trials. They looked at similar outcomes in terms of ACR20 [American College of Rheumatology 20% improvement], 50, and 70s, and PASI [Psoriasis Area and Severity Index] 75, 90, and 100s. They looked at enthesitis scores and dactylitis scores, quality-of-life measures. In both trials they did something quite different from what we’ve seen. They tried to get at the notion and interrogate the elements of spondylitis in the psoriatic arthritis populations. They allowed the investigator to identify every subject as having or not having spondylitis on the basis of a history of the elements of inflammatory back pain and then also on the basis of current or historical sacroiliac films that would demonstrate spondylitis. Then they looked at the results of these patients in terms of the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index] scores. This was very intriguing.

With all that being said and all those elements being evaluated in the course of the trials, there was 1 other factor that was looked at: fatigue, which is not unusual. But they looked at the pro-fatigue FACIT[Functional Assessment of Chronic Illness Therapy] score as a prespecified outcome—not a primary outcome but a secondary outcome. Because of the results of that, fatigue data were allowed in the label of the drug. What was disappointing to me is that they didn’t look at NAPSI [Nail Psoriasis Severity Index] scores, nail involvement scores. I was surprised about that. I would like to have seen those data. We all want to know if the drug really works for nail involvement.

Transcript Edited for Clarity