OBJECTIVES: Anti-CD74 antibodies (Abs) have been proposed as a diagnostic biomarker in axial spondyloarthritis (axSpA). The aims of this study were to evaluate the association of these Abs with disease activity parameters in axSpA and to assess their predictive value for tumour necrosis factor inhibitor (TNFi) treatment effectiveness. METHODS: Patients diagnosed with axSpA in the Swiss Clinical Quality Management registry with available biosamples and a measurement of IgA anti-CD74 Abs were included in this cohort study. We used a cut-off of 15 U/ml to define anti-CD74 Abs elevation. Associations of important disease characteristics with anti-CD4 Abs elevation and anti-CD74 Abs levels were evaluated using logistic and linear regression, respectively. For patients with an available biosample before TNFi initiation, we evaluated drug retention and estimated the hazard ratio of treatment discontinuation depending on anti-CD74 Abs elevation. RESULTS: Elevated IgA anti-CD74 Abs were found in 383/722 (53%) patients with axSpA and were significantly associated with older age, male sex, and elevated C-reactive protein (CRP). Among 310 patients starting TNFi treatment, no significant difference in drug retention was found between patients with and without elevated anti-CD74 Abs (HR 0.91, 95% CI 0.66 to 1.25). An increased Bath Ankylosing Spondylitis Disease Activity Index was found to be associated with a reduced TNFi retention whereas an elevated CRP was associated with a prolonged retention. CONCLUSIONS: Although elevated IgA anti-CD74 Abs are associated with CRP elevation, we could not demonstrate an additional value of this biomarker for predicting response to treatment with TNFi beyond CRP measurement.