OBJECTIVE: To systemically assess efficacy and safety of upadacitinib (UPA), a selective inhibitor of Janus kinase 1 (JAK1) in treatment of ankylosing spondylitis (AS). METHODS: Available databases were used to retrieve literatures of randomized controlled trials (RCTs) of UPA for AS treatment until February 2024. After that, the data were extracted and the Revman 5.4 software was used to conduct a meta-analysis. RESULTS: A total of 6 articles and 1653 patients (920 in a UPA group (15 mg, q.d) and 733 in a placebo group) were selected in this study. Respectively, UPA treatment significantly increased numbers of the AS patients having 40%, 20%, or partial remission (PR) improvement in assessment of spondylo arthritis international society (ASAS) (ASAS 40: 95%CI: 2.41-4.3, p <
0.00001
ASAS 20: 95%CI: 2.12-3.62, p <
0.00001
ASAS PR: 95%CI: 2.81-7.48, p <
0.00001), Bath ankylosing spondylitis disease activity index (BASDAI50) (95%CI: 2.28 ~ 4.10, p <
0.00001), quality of life (95%CI: 2.06 ~ 3.17, p <
0.00001), AS disease activity score low disease activity (ASDAS LDA) (95%CI: 3.07~9.96, p <
0.00001), ASDAS inactive disease (ID) (95%CI: 2.03 ~ 17.22, p = 0.001), short-form 36 physical component summary (SF-36PCS) (95%CI: 1.53 ~2.81, p <
0.00001), and markedly reduced ASDAS C-reactive protein (CRP) (95%CI: -1.22 ~ -0.42, p <
0.0001), total back pain score (95%CI: -2.01 ~ -0.51, p = 0.001), nighttime back pain score (95%CI: -1.96 ~ -0.54, p = 0.0006), spondylo arthritis research consortium of Canada magnetic resonance imaging (SPARCC MRI) spine score (95%CI: -7.78--3.50, p <
0.00001) and SPARCC MRI sacroiliac joint score (95%CI: -5.99 - -3.09, p <
0.00001), Bath ankylosing spondylitis function index (BASFI) score (95%CI: -1.45 ~ -0.81, p <
0.00001), Maastricht ankylosing spondylitis enthesitis score (MASES) (95%CI: -2.34~-0.35, p = 0.008). Except for neutropenia (95%CI: 1.25 ~ 15.60, p = 0.02), no other adverse effects (AEs) were significantly different between the UPA treatment and placebo. CONCLUSIONS: Through a literature analysis, it reveals that UPA offers significant therapeutic benefits to AS patients with a relatively high safety profile.