Efficacy and safety of Tumour necrosis factor inhibitors, Interleukin-17 inhibitors, and Janus kinase inhibitors in patients with non-radiographic axial spondyloarthritis: A systematic review and network meta-analysis.

Introduction: To systematically assess the efficacy and safety of tumour 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 and the Cochrane Register of Clinical Trials to find randomized controlled trials (RCTs) in patients with nr-axSpA published until June 2023, by two reviewers independently. Data extraction was carried out by two independent investigators. Stata 17.0 software and Review Manager 5.3 software were used to perform the data analysis. The results for binary and continuous variables were expressed as the values of odds ratio (OR) and mean difference (MD) and their 95% confidence interval (CI), respectively.

Results: A total of 10 RCTs involving 2,418 participants were included in the analysis. The efficacy rankings were: certolizumab pegol (CZP) 200 mg every 2 weeks (Q2W) > CZP 400 mg every 4 weeks (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 SpondyloArthritis international Society response criteria for 40% improvement (ASAS40); GOL > CZP 400 mg Q4W> BKZ > ADA > UPA > CZP 200 mg Q2W > ETN > BRO > SEC 150 mg NL > SEC 150 mg LD > PBO for Assessment of SpondyloArthritis international Society response criteria for 20% improvement (ASAS20). Except for BRO, all treatments resulted in a significant improvement in ASAS40 compared with PBO. In terms of safety, the ranking was: GOL > ADA > PBO > UPA > SEC 150 mg NL > BKZ > IXE > SEC 150 mg LD > ETN > CZP 200 mg Q2W for adverse events (AE). There was no statistical difference in serious adverse events (SAE) among all drugs compared to PBO.

Conclusions: Most TNFi could be more effective than JAKi and IL-17i. The safety of the therapies is generally good. However, the efficacy and safety of TNFi/IL-17i/JAKi remains to be further analyzed in studies with larger sample size and longer follow-up times.

Trial registration: This study has been registered in the International Prospective Register of Systematic Reviews (PROSPERO), with a registration number of CRD42023423725.