Comparative Efficacy of IL‐17A Inhibitors for Moderate‐to‐Severe Plaque Psoriasis: A Network Meta‐Analysis
Quan Zhou, Jingyue Ma, Xinzu Tong, Zhimin Wang, Huiping Wang, Powei Wu, Wangyang Zhao, Minghui Jiang, Ruixin Tan, Qintian Zhou, Zhidong WangBackground
Interleukin‐17A (IL‐17A) inhibitors demonstrate strong efficacy among biologic therapies for plaque psoriasis. However, comparative analyses within the IL‐17A class, particularly studies including newer agents vunakizumab and xeligekimab, remain scarce.
Objectives
To compare the efficacy and safety of four IL‐17A inhibitors (secukinumab, ixekizumab, vunakizumab, and xeligekimab) for adult patients with moderate‐to‐severe plaque psoriasis.
Methods
A systematic review and network meta‐analysis of randomized controlled trials (RCTs) compared four IL‐17A inhibitors with placebo. The protocol was registered with PROSPERO (CRD420251266904). Outcomes included PASI 75, 90, and 100 responses at Week 12. Treatments were ranked using the surface under the cumulative ranking curve (SUCRA). Safety outcomes were assessed descriptively.
Results
Seventeen RCTs with 11,044 patients were included. All IL‐17A inhibitors significantly outperformed placebo across efficacy endpoints at Week 12. Secukinumab 300 mg consistently ranked 1st for PASI 75 (SUCRA: 96.1%), PASI 90 (SUCRA: 93.8%), and PASI 100 (SUCRA: 95.3%). Vunakizumab 240 mg ranked 3rd for PASI 75 (SUCRA: 77.7%) but improved to 2nd place for PASI 90 (SUCRA: 80.0%) and PASI 100 (SUCRA: 81.9%), though with overlapping credible intervals relative to secukinumab 150 mg at these higher clearance endpoints. Secukinumab 150 mg ranked 2nd for PASI 75 (SUCRA: 82.1%) but 3rd place for PASI 90 (SUCRA: 73.0%) and 4th place for PASI 100 (SUCRA: 63.4%). Safety data were assessed descriptively only; no formal statistical comparison was performed. Observed adverse event rates varied across trials but could not be reliably compared due to differing observation windows and study designs.
Conclusion
Based on this network meta‐analysis of Week 12 efficacy, secukinumab 300 mg achieved the highest SUCRA rankings across PASI 75, 90, and 100 endpoints, though credible intervals overlapped with other active treatments and all comparisons were indirect. These rankings are hypothesis‐generating and should not be interpreted as evidence of definitive superiority; head‐to‐head trials are needed to confirm any between‐agent differences. Vunakizumab 240 mg and secukinumab 150 mg also showed robust efficacy; however, overlapping credible intervals limit firm distinctions between individual agents. While short‐term safety profiles appeared comparable across agents, long‐term real‐world evidence remains essential to fully characterize the benefit–risk profiles of newer biologics.