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5 Questions About the DISCOVER-1 Study in Psoriatic Arthritis
In the DISCOVER-1 clinical trial, Atul Deodhar, MD, MRCP, and colleagues sought to evaluate the safety and efficacy of guselkumab—an anti-interleukin 23p19 (anti-IL-23p19) monoclonal antibody—among patients with active psoriatic arthritis (PsA) who were naive to biologics or were previously treated with a tumor necrosis factor (TNF) α inhibitor.
Findings of the study showed that guselkumab improved joint and skin symptoms, physical function, and quality of life relative to placebo.
Rheumatology Consultant spoke with Dr Deodhar, a professor of medicine in the Division of Arthritis and Rheumatic Diseases at the Oregon Health and Science University School of Medicine, about the research. Findings were presented at the 2019 American College of Rheumatology (ACR)/Association of Rheumatology Professionals (ARP) Annual Meeting.
RHEUM CON: What are the disparities in care for patients with PsA?
Atul Deodhar: More treatment options are needed. Yes, we have TNF inhibitors, interleukin 17 (IL-17) inhibitors, and the interleukin 12 (IL-12)/interleukin 23 (IL-23) inhibitors. However, there are not enough treatments. For the skin manifestation of PsA, the psoriasis, more and more options are available and have shown great efficacy. Still, joint manifestations are a major issue with patients with PsA, and therapies have not shown an improvement from the anti-TNFs, which were the first biologics that came onto the market to manage PsA. Those anti-TNFs have created a ceiling effect that we just have not been able to get above. Guselkumab does not appear to be better than anti-TNFs, but it is a different strategy. We do not know which patients will or will not respond to which agent. The individualized treatment is not there. In daily practice, rheumatologists start with one treatment, and if that does not work, then we work with another, and then go on to a third agent if we have to. This is why we need more treatment options. If we knew which patients would respond to which agent, then we could target the therapy. We are not there yet.
RHEUM CON: How does an anti-IL-23p19 monoclonal antibody differ from other medications and targets in PsA?
AD: This is the first agent to have completed phase 3 studies with this particular antibody. It is an important antibody. We know that IL-23 is an important cytokine in the pathogenesis of spondyloarthritis. IL-23 is upstream and acts on certain cells which ultimately release IL-17. We know that IL-17 causes inflammation, joint damage, and enthesitis, and there already are IL-17 inhibitors on the market. Since IL-23 is important in the pathogenesis of PsA, we wanted to answer the question of whether blocking this particular cytokine will lead to improvement in patients’ signs and symptoms. Ultimately, we have shown with the study that it definitely does work.
RHEUM CON: Of the DISCOVER-1 study findings, which is most important for rheumatologists to know?
AD: There were several important outcomes. The first important outcome was that both dosages of guselkumab showed clinically significantly improvement in response to the composite measure ACR20 compared with placebo. The other 3 outcomes relate to skin, function, and quality of life, and are important from the patient’s point of view. The Investigator Global Assessment scale was used to monitor skin improvements; the scale showed that skin was dramatically better among patients in the guselkumab group compared with the placebo group. Function was measured via the Health Assessment Questionnaire (HAQ). Results of the HAQ showed statistically significant improvement in function compared to baseline in patients who received guselkumab compared to placebo. The physical component score of the Short Form 36 scale was used to measure quality of life. These scores also indicated a significant improvement in quality of life among patients in the guselkumab group compared with placebo.
RHEUM CON: Are there any concerns about adverse events (AEs) that rheumatologists should be aware of?
AD: The agent was found to be very safe in the DISCOVER-1 study. The reported infections were equal between placebo and guselkumab. The serious AEs were slightly higher in the placebo group compared with the guselkumab group. Of course, this was a very small study. I do not want to say this agent is safer than the placebo. At least, there are no signals of any serious side effects.
RHEUM CON: What are the next steps of the research?
AD: We are looking at different aspects of PsA, because the condition has multiple domains. PsA includes joint domains, enthesitis domains, and some people have spinal disease with psoriatic spondyloarthritis. There are enough patients in this study to look at enthesitis, dactylitis, and spine disease. We want to determine if guselkumab improves the patients’ overall well-being. There are several aspects of psoriatic disease that will be teased out from the data that has been collected in the DISCOVER-1 clinical trial.
Reference:
Deodhar A, Helliwell P, Boencke W-H, et al. Guselkumab, an anti-interleukin-23p19 monoclonal antibody, in patients with active psoriatic arthritis who were biologic-naïve or prior TNFα inhibitor-treated: week 24 results of a phase 3, randomized, double-blind, placebo-controlled study [abstract 807]. Arthritis Rheumatol. 2019;71(suppl 10). Presented at: 2019 ACR/ARP Annual Meeting; November 8-13, 2019; Atlanta, GA. https://acrabstracts.org/abstract/guselkumab-an-anti-interleukin-23p19-monoclonal-antibody-in-patients-with-active-psoriatic-arthritis-who-were-biologic-naive-or-prior-tnf%CE%B1-inhibitor-treated-week-24-results-of-a-phase-3-rando/.
