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- Presentation
Argument for IL-17 Over IL-23 in Psoriatic Arthritis Prevention and Treatment
Description
The speaker argues that IL-17 is the better target than IL-23 for preventing and treating psoriatic arthritis, emphasizing that the decision should be based on data rather than narrative. He says psoriatic arthritis is mechanistically heterogeneous and involves IL-17 production from multiple immune pathways not fully controlled by IL-23, including mast cells, innate lymphoid cells, and gamma-delta cells, especially in synovial fluid and enthesis-related disease. He notes that IL-17 appears important across multiple disease domains, including axial disease, where IL-23 has not shown efficacy and is not recommended in guidelines. He also points to current efficacy evidence, saying IL-17 inhibitors generally perform better and citing a head-to-head study in which bimekizumab outperformed an IL-23 approach across endpoints, while transcriptomic findings suggested IL-17 blockade can downregulate IL-23, implying a feedback loop rather than a simple downstream pathway. He cautions that observational prevention studies favoring IL-23 may be biased by channeling and protopathic bias, since patients with early joint symptoms may have been preferentially placed on IL-17 or TNF drugs. Although he acknowledges emerging prospective prevention/interception data, he concludes that the mechanistic and efficacy data currently favor IL-17, urging the audience to vote based on the numbers and choose IL-17.
View moreConclusions
- The presentation argues that IL-17 inhibition should be prioritized over IL-23 inhibition when the goal is preventing psoriatic arthritis.
- Psoriatic arthritis appears biologically heterogeneous, with important IL-17 activity that can arise independently of IL-23.
- Because different PsA domains are driven by different pathways, a treatment that works broadly across peripheral arthritis, enthesitis, dactylitis, axial disease, and radiographic outcomes is preferred.
- The speaker concludes that IL-17 inhibitors currently have stronger established efficacy across PsA domains than IL-23 inhibitors.
- Recent head-to-head and transcriptomic data are presented as evidence that IL-17 blockade can outperform IL-23 blockade and may even downregulate IL-23 expression.
- The observational studies suggesting IL-23 benefit are viewed as vulnerable to confounding, channeling bias, and protopathic bias, so they are considered insufficient for firm conclusions.
- Early interception and prospective data are interpreted as suggestive that IL-17 inhibition may reduce symptoms or subclinical inflammation in high-risk psoriasis patients.
- Overall, the talk concludes that the weight of current evidence favors IL-17 inhibitors as the best first choice for PsA prevention, while acknowledging that definitive prospective prevention trials are still needed.
- Nature Reviews Rheumatology | Volume 21 | April 2025 | 237-248
- GRAPPA 2021 recommendations
- Efficacy and safety of pharmacological treatment of psoriatic arthritis: a systematic literature research informing the 2023 update of the EULAR recommendations for the management of psoriatic arthritis#10.1136/ard-2024-225534
- Interleukin-23 versus Interleukin-17 Inhibitors in Preventing Incidental Psoriatic Arthritis in Patients with Psoriasis: A Real-World Comparison From the TriNetX US Collaborative Network#10.1007/s40259-025-00705-5