IL-17 ligand-targeting inhibitors in psoriatic arthritis: a focused systematic review and network meta-analysis of efficacy, safety, and certainty of evidence.

BACKGROUND: IL-17 pathway inhibitors are established treatments for active psoriatic arthritis (PsA), but comparative evidence within this therapeutic class remains limited. We compared the efficacy, safety, treatment rankings, and certainty of evidence for established and emerging IL-17 pathway inhibitors in adults with active PsA. METHODS: We conducted a PRISMA-compliant systematic review and network meta-analysis. MEDLINE via PubMed, Embase via Ovid, CENTRAL, ClinicalTrials.gov, and the EU Clinical Trials Register were searched from January 1, 2010, to January 18, 2026. Eligible studies were phase 2 or phase 3 randomized controlled trials in adults with PsA. The primary outcome was ACR50 at Weeks 12-16. Secondary outcomes included ACR20, ACR70, PASI90, minimal disease activity, HAQ-DI, safety outcomes, Week-24 outcomes, and descriptive Week-52 outcomes. Frequentist random-effects network meta-analysis was performed; certainty was assessed using CINeMA. RESULTS: Sixteen RCTs were included. The primary ACR50 network comprised eight RCTs and ten treatment nodes. All active treatments were superior to placebo for ACR50 at Weeks 12-16, with negligible heterogeneity (τ² = 0; I² = 0%) and no important incoherence. Ixekizumab Q2W had the highest ACR50 P-score, followed by bimekizumab 160 mg with loading and ixekizumab Q4W; however, active-treatment confidence intervals overlapped. Secondary outcomes showed consistent improvements in joint, skin, multidomain, and functional endpoints. Sonelokimab and izokibep showed favorable exploratory estimates but very low certainty. Serious adverse events and discontinuations were not clearly increased versus placebo. Bimekizumab showed a modest increase in infection risk and a higher Candida signal; IBD events were rare. CONCLUSION: IL-17 pathway inhibitors are effective short-term treatments for active PsA. Rankings suggest potential within-class differences, but indirect comparisons and overlapping confidence intervals limit definitive superiority claims. Candida risk and patient-specific factors should inform individualized treatment selection. The protocol was registered in PROSPERO (CRD420251156756). SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251156756, identifier CRD420251156756.