OBJECTIVE: To compare the clinical and sociodemographic characteristics of Ibero-American patients with radiographic axial spondyloarthritis (r-axSpA) to those of European patients with r-axSpA, with a particular focus on the influence of HLA-B27. METHODS: This was an observational, cross-sectional, and multicenter study of patients who fulfilled the European Spondyloarthropathy Study Group criteria for SpA from the Registry of Spondyloarthritis of Spanish Rheumatology (REGISPONSER) and Ibero-American Registry of Spondyloarthropathies (RESPONDIA). Univariate and multivariate analyses between European and Ibero-American populations stratified by HLA-B27 status were conducted. Race stratification (White, Black American, and American Indian) was also performed to evaluate clinical differences according to HLA-B27. RESULTS: A total of 2592 patients with a clinical diagnosis of r-axSpA were included in the analysis: 1083 (41.8%) Ibero-American patients and 1509 (58.2%) European patients. Among the patients who were HLA-B27 positive, Ibero-American status was independently associated with conventional synthetic disease-modifying antirheumatic drug (csDMARD) intake (odds ratio [OR] 4.21), arthritis (OR 2.33), enthesitis (OR 6.01), dactylitis (OR 6.10), severe structural damage (Bath Ankylosing Spondylitis Radiological Index [BASRI]
OR 1.12), and poor functionality (Bath Ankylosing Spondylitis Functional Index
OR 1.40). Multivariate analysis of patients who were HLA-B27 negative revealed that Ibero-American status was independently associated with enthesitis (OR 11.67), csDMARDs (OR 15.51), and total BASRI (OR 1.34). Clinical manifestations also varied across racial groups, with differences noted in the prevalence of peripheral joint manifestations, such as more arthritis and enthesitis in American Indian patients than in White and Black American patients. CONCLUSION: Ibero-American patients with r-axSpA in our study exhibit more peripheral manifestations, more structural damage, and worse functionality than European patients, regardless of the presence of HLA-B27.