Therapeutic efficacy of molecular-targeted drugs for enthesitis in patients with PsA: a network meta-analysis.

Objectives: Enthesitis plays a key role in the pathogenesis of PsA. This study aimed to evaluate the efficacy of molecular-targeted therapies for enthesitis in patients with PsA.

Methods: In this network meta-analysis (PROSPERO registration number: CRD42024590257), studies published up to April 2025 were searched in PubMed, Web of Science, Scopus and ClinicalTrials.gov. Only randomized controlled trials assessing molecular-targeted therapies for enthesitis in PsA were included. The primary outcomes were enthesitis resolution rates and Leeds enthesitis index score reductions at 12 and 24 weeks. A random-effects model was employed to calculate risk differences (RDs) or standardized mean differences (SMDs) with 95% confidence intervals (CIs), analysing both drug classes and individual agents.

Results: Out of 5762 screened studies, 28 randomized controlled trials were included, encompassing 10 383 patients with PsA presenting with enthesitis. Therapies included TNF-alpha inhibitors, Janus kinase inhibitors, IL-17/IL-17 receptor inhibitors, IL-23 inhibitors and a cytotoxic T lymphocyte-associated antigen-4 immunoglobulin. At 24 weeks, upadacitinib significantly improved the enthesitis resolution rate [RD: 11.24 (95% CI: 4.26 to 18.23)] and reduced the Leeds enthesitis index scores [SMD: -0.72 (95% CI: -1.36 to -0.09)] compared with adalimumab; meanwhile, other Janus kinase inhibitors did not. Certolizumab also reduced the Leeds enthesitis index scores [SMD: -0.92 (95% CI: -1.72 to -0.13)].

Conclusion: This network meta-analysis identified the more therapeutic efficacy of upadacitinib and certolizumab for enthesitis in patients with PsA than those of other molecular-targeted drugs. Notably, efficacy varied among molecular-targeted therapies, even within drug classes, underscoring the need for tailored therapeutic strategies.