OBJECTIVES: To develop a consensus-based expert definition of difficult-to-manage (D2M) axial spondyloarthritis (axSpA), incorporating treatment-refractory (TR) disease. METHODS: A literature review was conducted in 2022 to identify potential definitions for D2M/TR axSpA from prior studies, followed by a 2-round Delphi consensus process conducted in 2022 and 2023 to identify components of D2M axSpA. Based on the results of the Delphi process, a draft of the D2M axSpA definition was developed and presented to the expert task force, including patient representation, and, subsequently, to the Assessment of SpondyloArthritis International Society (ASAS) membership for endorsement in January 2024. RESULTS: Consensus was reached on a D2M definition encapsulating treatment failure (treatment according to the ASAS-European Alliance of Associations for Rheumatology recommendations and failure of ≥2 biological or targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action unless contraindicated), suboptimal disease control, and physician or patient acknowledgement of problematic signs/symptoms in patients diagnosed with axSpA by the rheumatologist. This definition represents a broad concept that includes various reasons that lead to an unsatisfactory treatment outcome. TR axSpA is covered by the D2M definition but requires a history of treatment failure, the presence of objective signs of inflammatory activity, and the exclusion of noninflammatory reasons for nonresponse. The proposed D2M definition incorporating TR disease was endorsed by ASAS at the annual meeting in January 2024, with 89% votes (109/123) in favour of it. CONCLUSIONS: The ASAS D2M axSpA definition, including TR disease, allows for identifying patients with unmet needs, paving the way for further research in this condition and its clinical care improvement.