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ABSTRACT Objective: The development of anti-drug antibodies against tumor necrosis factor inhibitors is a likely explanation for the failure of TNF-inhibitors in patients with spondyloarthritis. Our study determined the existence and clinical implications of ADAbs in axial spondyloarthritis patients. Methods: According to the Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis, patients treated with adalimumab or infliximab were recruited consecutively. Serum samples were collected at enrollment to measure anti-drug antibodies and drug levels. Results: Of 100 patients, the mean duration of current TNF inhibitor use was 22.3 ± 17.9 months. Anti-drug antibodies were detected in 5 of 72 adalimumab users compared to 5 of 28 infliximab users (6.9% vs. 17.9%). Anti-drug antibodies-positive patients had a significantly higher body mass index than anti-drug antibodies-negative patients among both adalimumab (28.4 ± 5.9 kg/m2 vs. 24.3 ± 2.9 kg/m2, respectively, p = 0.01) and infliximab users (25.9 ± 2.8 kg/m2 vs. 22.6 ± 2.8 kg/m2, respectively, p = 0.02). During the median 15-month follow-up period, drug discontinuation occurred more frequently in the anti-drug antibodies-positive group than the anti-drug antibodies-negative group (30.0% vs. 6.5%, respectively, p = 0.04). In logistic regression, anti-drug antibodies positivity (OR = 5.85, 95% CI 1.19-28.61, p = 0.029) and body mass index (OR = 4.35, 95% CI 1.01-18.69, p = 0.048) were associated with a greater risk of stopping TNF inhibitor treatment. Conclusions: Our result suggests that the presence of anti-drug antibodies against adalimumab and infliximab as well as a higher body mass index can predict subsequent drug discontinuation in axial spondyloarthritis patients.