Introduction: A growing number of randomized controlled trials (RCTs) have demonstrated the effectiveness of tumor necrosis factor-α (TNF-α) inhibitors in treating non-radiographic axial spondyloarthritis (nr-axSpA). This study aimed to evaluate the efficacy of TNF-α inhibitors in the treatment of nr-axSpA. Methods: PubMed, EMBASE, Web of Science, and the Cochrane Library databases were systematically searched for relevant RCTs using specific keywords up to June 2023. The primary outcome was the proportion of patients who achieved Assessment in SpondyloArthritis international Society 40% (ASAS40). Secondary outcomes included ASAS20, Bath Ankylosing Spondylitis Disease Activity Index 50% (BASDAI50), ASAS partial remission, and ASAS5/6. Results: A total of eight RCTs involving 1,376 patients were included. Patients receiving anti-TNF therapy exhibited a higher rate of ASAS40 (pooled RR = 2.36; 95% CI: 1.63–3.42; p < 0.001). In addition, the TNF-α inhibitor group showed higher BASDAI50 rates (pooled RR = 2.06; 95% CI: 1.48–2.89), ASAS20 rates (pooled RR = 1.48; 95% CI: 1.31–1.67), ASAS partial remission rates (pooled RR = 2.33; 95% CI: 1.58–3.43), and ASAS5/6 rates (RR = 3.46; 95% CI: 2.05–5.83) than the placebo group. Conclusion: The TNF-α inhibitors were effective in treating nr-axSpA.

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