COMMENTARY

New Psoriasis Treatments: A Primer

Jeffrey Liu; April W. Armstrong, MD, MPH

Disclosures

August 17, 2021

The negative effects of uncontrolled plaque psoriasis on a patient's quality of life are well known. Fortunately, increased understanding of the pathogenesis of plaque psoriasis over the past two decades has led to the development of new highly effective therapies, most notably systemic biologic agents and emerging novel oral and topical agents that target specific cytokines and enzyme receptors involved in the disease process. Here, we highlight exciting data from recent studies demonstrating the effectiveness of these newer-generation therapies in treating and maintaining skin clearance in patients with moderate to severe psoriasis.

Comparing Efficacies of IL-17, IL-23, and TNF Inhibitors

The advent of interleukin (IL)–17 inhibitors (brodalumab, ixekizumab, secukinumab) and IL-23 inhibitors (guselkumab, risankizumab, tildrakizumab) have greatly improved skin clearance in patients with plaque psoriasis. Overall, the initiation of IL-17 and IL-23 inhibitors in patients with psoriasis has gradually exceeded that of tumor necrosis factor-alpha (TNF-alpha) inhibitors. Although head-to-head trials comparing IL-17 and IL-23 inhibitors with TNF-alpha inhibitors can be highly informative, they are not available for all combinations of systemic medications, making it difficult for clinicians to know how IL-17, IL-23, and TNF-alpha inhibitors directly compare with one another. Therefore, indirect comparison methods, such as network meta-analyses and literature reviews, can help guide clinical decision-making.

One recent meta-analysis of 60 randomized clinical trials by Armstrong and colleagues assessed the comparative effectiveness of oral and biologic treatments. They found high response rates and skin clearance in both short-term (10-16 weeks from baseline) and long-term (44-60 weeks from baseline) courses of brodalumab, guselkumab, ixekizumab, and risankizumab. Short-term efficacy, as assessed by estimated Psoriasis Area and Severity Index (PASI) 75%, 90%, and 100% (PASI 75, 90, and 100) response rates at 10-16 weeks were highest in brodalumab, guselkumab, ixekizumab, and risankizumab (with 95% probability) when compared with the TNF-alpha inhibitors apremilast, tildrakizumab, and ustekinumab. There were no significant differences in PASI responses among brodalumab, guselkumab, ixekizumab, and risankizumab at 10-16 weeks. Importantly, patients receiving these medications had high PASI response rates throughout the entire maintenance period (44-60 weeks from baseline). At the end of the maintenance period, PASI 90 rates were significantly higher in patients receiving risankizumab vs patients receiving ixekizumab and secukinumab; moreover, PASI 100 rates were significantly higher in patients receiving brodalumab, ixekizumab, and risankizumab vs patients receiving secukinumab. Based on these findings, additional head-to-head prospective studies are warranted to compare these biologics with emerging novel systemic treatments.

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