{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:33:49Z","timestamp":1789875229938,"version":"4.0.1"},"reference-count":22,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Musculoskeletal"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The concept of difficult-to-manage axial spondyloarthritis (D2M-axSpA) has recently been introduced to describe patients with a persistent disease burden despite appropriate treatment. However, its real-world prevalence and associated clinical features remain insufficiently characterised.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To estimate the prevalence of D2M and treatment-refractory (TR) axSpA in routine clinical practice, identify factors associated with D2M, and assess the consistency of selected D2M-associated features across different cohorts.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design and methods:<\/jats:title>\n                    <jats:p>A cross-sectional study was conducted in 252 patients with axSpA from two Italian tertiary centres. The 2024 Assessment of Spondyloarthritis International Society consensus-based definition was applied to identify D2M and TR axSpA. Clinical, laboratory and imaging characteristics were compared between D2M and non-D2M patients. Factors independently associated with D2M were evaluated using multivariable logistic regression. To explore consistency across populations, an exploratory meta-analysis was performed using harmonised data from the published Argentinian Reuma-Check cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Among 252 patients with axSpA, 16 (6.3%) fulfilled the definition of D2M, and 8 (3.2%) met criteria for TR axSpA. Patients with D2M exhibited higher disease activity (Axial Spondyloarthritis Disease Activity Score 2.50\u2009\u00b1\u20090.62 vs 1.24\u2009\u00b1\u20090.65;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001), greater axial pain (2.50\u2009\u00b1\u20092.75 vs 0.80\u2009\u00b1\u20091.63;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.017) and worse global assessments (Patient Global Assessment 3.20 vs 1.16;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In multivariable analysis, fibromyalgia (odds ratios (OR) 5.5, 95% confidence interval (CI): 1.2\u201325.6) and a history of uveitis (OR 3.3, 95% CI: 1.0\u201311.1) were independently associated with D2M status. Current nonsteroidal anti-inflammatory drug (NSAID) use (OR 3.8, 95% CI: 1.2\u201311.9) was also associated with D2M, most likely reflecting higher symptom burden rather than a causal relationship. Meta-analytic findings identified psoriasis (risk ratios (RR) 2.17;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.008), smoking (RR 1.53;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.045), uveitis (RR 2.45;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.044) and radiographic structural damage (RR 1.84;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.004) as consistent features associated with D2M axSpA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>D2M axSpA was identified in approximately 6.3% of patients, while 3.2% fulfilled criteria for TR axSpA. Fibromyalgia, NSAID use and uveitis were independently associated with the D2M phenotype, whereas meta-analytic evidence highlighted additional associations with psoriasis, smoking and structural damage. These findings support the multifactorial nature of D2M axSpA, in which both inflammatory and non-inflammatory mechanisms contribute to disease complexity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/1759720x261434275","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:29:46Z","timestamp":1788146986000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Prevalence and clinical factors associated with difficult-to-manage axial spondyloarthritis: a multicentre Italian cohort study with meta-analysis"],"prefix":"10.1177","volume":"18","author":[{"given":"Giulio","family":"Forte","sequence":"first","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilberto","family":"Cincinelli","sequence":"additional","affiliation":[{"name":"University of Milan and ASST PiniCTO \u2013 Presidio Gaetano Pini, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Mauro","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Pantano","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Ferrito","sequence":"additional","affiliation":[{"name":"University of Milan and ASST PiniCTO \u2013 Presidio Gaetano Pini, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saviana","family":"Gandolfo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Naples, Italy"},{"name":"Rheumatology Unit, Ospedale del Mare, ASL Napoli 1 Centro, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Amati","sequence":"additional","affiliation":[{"name":"University of Milan and ASST PiniCTO \u2013 Presidio Gaetano Pini, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Ciancio","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi Vanvitelli\u2019, Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Longo","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u2018Luigi 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