IL-17 Class Inhibitors and Plaque Psoriasis: Not All Biologics Relapse Equally

In patients with moderate-to-severe plaque psoriasis, recent meta-analyses compared efficacies among biologics and time to relapse after treatment withdrawal; however, there was notable heterogeneity in the clinical trials and their criteria used to define relapse. Furthermore, while biologics are effectively grouped into treatment classes based on their mechanisms of action (ie, anti-interleukin (IL)-23 class, anti-IL-17 class), not all biologics should necessarily be grouped into a class effect. For example, the anti-IL-17 class is heterogeneous in their mechanisms of action due to the variety of cytokines and receptors antagonized along with their accompanying gene expression changes in psoriatic disease. Therefore, we performed an in-depth assessment of biologics comprising the anti-IL-17 class and their associated pharmacokinetics (PK). We identified differences in PK parameters that may augment our understanding of how these biologics differ in function and explain variations in time to relapse of psoriatic disease after treatment withdrawal.

A PubMed literature search was performed and articles screened to only include double-blind, randomized, placebo or comparator-controlled trials. The remaining articles were screened to ensure inclusion of a treatment withdrawal period and to confirm they investigated and defined relapse.

We identified five unique randomized controlled trials that examined time to relapse after treatment discontinuation for anti-IL-17 biologics. Brodalumab, an IL-17RA antagonist, consistently demonstrated the quickest time to relapse, whereas bimekizumab, the first-in-class dual IL-17A and IL-17F antagonist, demonstrated the longest time to relapse.

There is heterogeneity in both the criteria for treatment success prior to undergoing treatment withdrawal as well as relapse criteria. The only relapse datapoints shared by all four anti-IL-17 class biologics examined were median time to loss of PASI-75 and PASI-90.

Differences in time to relapse after treatment discontinuation following treatment success can be attributed to both differences in biologic PK properties and mechanisms of action. These results warrant further investigation into the role of IL-17F in the pathogenesis of plaque psoriasis, as targeting this isoform appears to confer synergistic therapeutic benefit compared to targeting the IL-17A isoform alone. Furthermore, the classic understanding of IL-17RA blockade with brodalumab must be revisited as IL-17F was found to partially bind and signal through IL-17RA despite the presence of brodalumab.