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

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.

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.

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)].

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.