Efficacy and Safety of Tumor Necrosis Factor Inhibitors, Interleukin-17 Inhibitors, and Janus Kinase Inhibitors in Patients with Non-Radiographic Axial Spondyloarthritis: A Systematic Review and Network Meta-Analysis.

Abstract

Introduction: The aim of the study was to systematically assess the efficacy and safety of tumor necrosis factor inhibitors (TNFi), interleukin-17 inhibitors (IL-17i), and Janus kinase inhibitors (JAKi) in patients with non-radiographic axial spondyloarthritis (nr-axSpA).

Methods: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Register of Clinical Trials, and Scopus to find randomized controlled trials in patients with nr-axSpA published until June 2023. Stata 17.0 software and Review Manager 5.4 software were used for data analysis. The results for binary and continuous variables were expressed as the values of odds ratio and mean difference and their 95% confidence interval, respectively.

Results: For Assessment of SpondyloArthritis International Society Response Criteria for 40% improvement (ASAS40), the efficacy of the 12 interventions ranked as follows: certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W) > CZP 400 mg Q4W > golimumab (GOL) > bimekizumab (BKZ) > adalimumab (ADA) > upadacitinib (UPA) > etanercept (ETN) > brodalumab (BRO) > ixekizumab (IXE) > secukinumab (SEC) 150 mg no loading (NL) > SEC 150 mg loading dose (LD) > placebo (PBO). For assessment of ASAS20, the NMA results were ranked as follows: GOL > CZP 400 mg Q4W> BKZ> ADA > UPA > CZP 200 mg Q2W > ETN > BRO > SEC 150 mg NL > SEC 150 mg LD > PBO, and GOL > ADA > PBO > UPA > SEC 150 mg NL > BKZ > IXE > SEC 150 mg LD > ETN > CZP 200 mg Q2W for adverse events.

Conclusions: Most TNFi may be more effective than JAKi and IL-17i. They were all well tolerated. However, the efficacy and safety of TNFi/IL-17i/JAKi remain to be further analyzed in studies with larger sample sizes and longer follow-up times.