<p>Although long-term clinical trial data for plaque psoriasis therapies indicate that patients appear to maintain treatment response over time, it can be difficult to generalize these results to the general population, as patients who stay in these studies are responders and are therefore an enriched population. Drug persistence studies, on the other hand, can provide a real-world perspective on drug-switching behaviors and medication adherence. At the recent <strong>2025 Fall Clinical Dermatology Conference</strong>, long-term drug persistence analyses were reviewed, with implications for the consideration of IL-23 inhibitors in clinical practice.</p> <p><br></p> <p><em>Following this presentation, featured expert Eingun James Song, MD, FAAD, was interviewed by </em>Conference Reporter<em> Associate Editor-in-Chief Christopher Ontiveros, PhD. Clinical perspectives from Dr Song on these findings are presented here.</em></p>

IL-23 is a pivotal cytokine that stabilizes and sustains the pathogenic Th17 cell populations driving psoriatic inflammation. Once activated, these IL-23–dependent cells produce effector cytokines (particularly IL-17A, IL-17F, and IL-22) that reinforce a self-amplifying inflammatory loop in keratinocytes and the broader immune network. By targeting IL-23 upstream, we disrupt the maintenance and survival of these pathogenic lymphocytes rather than simply blocking their downstream cytokine products. Clinically, this upstream effect explains why disease recurrence after stopping IL-23 inhibitors can take many months, whereas therapies that target downstream cytokines tend to be associated with a shorter time to disease recurrence.

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In real-world studies of plaque psoriasis therapies, drug survival—or drug persistence—is a key metric that encompasses effectiveness, safety, tolerability, patient satisfaction, and even insurance or access considerations. It answers the following important question: If a patient starts therapy X, how long do they remain on it?

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Open-label long-term extension data from plaque psoriasis clinical trials consistently show that patients maintain strong responses over time. However, these results may not fully represent everyday practice, as trial extensions tend to follow an enriched group of patients who are already responding well and are able to remain on therapy. Drug persistence studies, in contrast, offer a more realistic view of how treatments perform in the real world, capturing patterns of continuation, switching, and discontinuation across a broader, more representative patient population.

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At the 2025 Fall Clinical Dermatology Conference, James Q. Del Rosso, DO, Bruce Strober, MD, and I reviewed 2 real-world studies evaluating IL-23 inhibitors. The first was an analysis from the OM1 psoriasis registry, a large US data set with highly granular clinical information. Because it integrates electronic health record details, including disease severity, body surface area, and both medical and pharmacy claims, we can track treatment changes and any complications that occur, making this an exceptionally robust source of real-world evidence.

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Over a 3-year period, the analysis showed that roughly one-third of patients switched from 1 biologic to another. Considering the strength and consistency of our psoriasis therapies, that is a surprisingly high—and somewhat concerning—rate of treatment change. When focusing specifically on drug persistence, IL-23 inhibitors, particularly risankizumab and guselkumab, demonstrated the highest durability over the 3-year period. Their persistence rates were 2 to 4 times higher than those observed with other biologic classes, including the TNF inhibitor adalimumab and the IL-17A inhibitor secukinumab. Overall, IL-23 inhibitors showed the highest drug persistence of any class evaluated.

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Several factors were associated with a higher likelihood of treatment switching. Female patients consistently showed increased treatment switching. Individuals aged 51 to 64 were also more likely to switch therapies—potentially reflecting shifts in out-of-pocket costs as patients transition from commercial insurance to Medicare. In addition, patients who were already receiving an immunomodulatory therapy at baseline were more prone to switch biologics over time, which most likely reflects a more treatment-refractory population.

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The second data set that we discussed during our session at this year’s Fall Clinical Dermatology Conference came from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a large registry spanning the United Kingdom and Ireland. This analysis evaluated drug survival over roughly 2 years, with results stratified by the reason for discontinuation, such as a lack of efficacy or tolerability. In BADBIR, risankizumab and guselkumab showed the lowest rates of discontinuation and switching due to inefficacy, and, as expected, adverse event–related discontinuations were low across all biologic classes.

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Overall, both data sets showed a clear and consistent pattern: IL-23 inhibitors demonstrated the strongest drug persistence. These therapies pair excellent efficacy with favorable long-term safety. Their less frequent dosing schedule compared with that of IL-17 or TNF inhibitors also supports better adherence. In addition, withdrawal studies indicate that brief delays in dosing rarely affect disease control. Finally, access and insurance coverage for IL-23 inhibitors remain strong, further contributing to their high persistence in real-world practice.