{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T03:34:23Z","timestamp":1789875263653,"version":"4.0.1"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100014801","name":"Ankara Y\u0131ld\u0131r\u0131m Beyaz\u0131t University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014801","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Rheumatol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study was aimed at determining the prevalence of difficult-to-treat (D2T) axial spondyloarthritis (axSpA) and identifying main associated factors for D2T axSpA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>This multicenter observational cross-sectional study included axSpA patients from the BioSTaR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) from February 1, 2019, to January 1, 2025. Data from 1800 axSpA patients who have previously used or are currently using at least one biologic\/targeted synthetic disease-modifying antirheumatic drug were analyzed. Patient data included demographic characteristics, body mass index (BMI), marital status, smoking and alcohol use, family history of SpA, and presence of comorbidities. The parameters related to SpA such as disease duration, type of axSpA (radiographic\/non-radiographic), HLA-B27 status, the presence of extra-musculoskeletal manifestations (uveitis, psoriasis, and inflammatory bowel disease), arthritis, enthesitis, and dactylitis were also recorded. Comorbidities including hypertension, cardiovascular disease, diabetes, obesity, and hyperlipidemia were recorded, and Charlson Index scores were evaluated. Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) and disease activity in means of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP) were also recorded. All medication history and currently used medications for axSpA and other diseases were noted. D2T and non-D2T axSpA patients were classified according to the suggested extrapolated definition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 1800 axSpA patients recorded in the BioSTaR database, 204 (11.3%) were classified as D2T axSpA. Data of these patients were compared to the data from 1596 non-D2T axSpA patients. Disease duration was longer in D2T patients (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.025). The presence of radiographic disease was more frequent in the D2T group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.047). In means of MASES and ASDAS-CRP, higher scores were recorded in the D2T group (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Enthesitis and psoriasis were more frequent in the D2T group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006). Regarding comorbidities, hypertension and cardiovascular diseases were more frequent in the D2T group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). The risk of D2T axSpA increased 2.37-fold with the presence of r-axSpA (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018), 1.92-fold with the presence of hypertension (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006), 2.12-fold with the presence of obesity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.024), and 3.63-fold with the presence of psoriasis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.004). Every 1-point increase in MASES increased D2T risk 1.08-fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.017), and every 1-point increase in ASDAS-CRP increased D2T risk 1.62-fold (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      In conclusion, 11.3% of patients with axSpA met the proposed criteria for D2T axSpA. This subgroup was characterized by longer disease duration, higher frequency of r-axSpA, enthesitis, and psoriasis, as well as elevated MASES, CRP, ASDAS-CRP, and BASDAI scores. Hypertension and cardiovascular comorbidities were also significantly more prevalent among D2T patients. These parameters represent potential contributors to treatment complexity and should be carefully considered in therapeutic decision-making. In cases of suboptimal treatment response, reassessment and optimal management of comorbidities are essential, as comorbid conditions can increase disease burden and diminish therapeutic efficacy. Comprehensive care for axSpA should therefore include targeted management of accompanying comorbidities in parallel with disease-specific therapy. Monitoring blood pressure, optimizing body weight, and encouraging smoking cessation are particularly important. Additionally, concomitant rheumatic diseases such as psoriasis, uveitis, or inflammatory bowel disease should be actively evaluated and treated, given their association with more severe disease and reduced treatment response.\n                      <jats:table-wrap>\n                        <jats:table>\n                          <jats:tbody>\n                            <jats:tr>\n                              <jats:td align=\"left\" colspan=\"2\">\n                                <jats:bold>Key Points<\/jats:bold>\n                                \u2022\n                                <jats:italic>Prospectively collected data of 1800 axial spondyloarthritis patients were assessed for this cross-sectional study<\/jats:italic>\n                                .\u2022\n                                <jats:italic>11.3% of axial spondyloarthritis patients were identified as difficult-to-treat<\/jats:italic>\n                                .\u2022\n                                <jats:italic>Longer disease duration and presence of radiographic axial spondyloarthritis, enthesitis, and psoriasis are more prevalent in difficult-to-treat axial spondyloarthritis patients<\/jats:italic>\n                                .\u2022\n                                <jats:italic>Factors and comorbidities complicating axial spondyloarthritis treatment should be considered in treatment plans<\/jats:italic>\n                                .\n                              <\/jats:td>\n                            <\/jats:tr>\n                          <\/jats:tbody>\n                        <\/jats:table>\n                      <\/jats:table-wrap>\n                    <\/jats:p>\n                  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