Targeting Structural Damage in Psoriatic Arthritis: The Impact of Early Recognition and Timely Intervention - Episode 11
Differentiating Between IL-23 Inhibitors in Psoriatic Disease
Experts discuss the structural and mechanistic differences between 2 IL-23 p19 inhibitors, exploring how variations in Fc region design may influence their localization to inflamed sites and clinical efficacy—particularly in preventing structural damage—and highlight challenges in assessing progression in psoriatic arthritis trials, suggesting that advanced imaging such as ultrasound could improve future evaluations.
From a clinical and mechanistic standpoint, both medications target the IL-23 p19 subunit but differ structurally, which may influence their clinical effects. One is fully human with a wild-type Fc backbone that can bind to CD64, a high-affinity receptor found on myeloid cells producing IL-23. This binding potentially allows the drug to localize directly to inflamed sites, enhancing its ability to neutralize IL-23 where it is most active. The other drug is humanized with an Fc region mutation designed to silence immune recognition, which might reduce immune system engagement but may limit its ability to concentrate at inflammation sites. These differences could explain variations in clinical efficacy, such as stronger effects on structural damage or symptom improvement seen in some study data.
Clinically, these mechanistic distinctions translate into potential practical benefits. For example, one medication’s dosing flexibility—with options to shorten intervals for heavier or biologically experienced patients—may help manage breakthrough symptoms more effectively. Although head-to-head trials are lacking, numerical trends suggest subtle differences in outcomes such as ACR scores and fatigue, with radiographic inhibition being a key differentiator. Meanwhile, the other agent’s radiographic data have not shown statistical significance, partly due to minimal disease progression in the trial population, leaving some uncertainty about its effectiveness in preventing joint damage.
Assessing structural progression in psoriatic arthritis is inherently challenging because changes are slow and may not appear in placebo groups over typical trial durations. Moreover, evolving ethical standards limit the length of placebo-controlled phases, complicating data collection. In this context, innovative imaging tools such as ultrasound—which can detect erosions earlier and more sensitively—may offer valuable surrogate end points to better evaluate treatment effects on joint damage moving forward.
