{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:31:28Z","timestamp":1787725888415,"version":"build-2784847793"},"reference-count":140,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Ankylosing spondylitis (AS) is a prototypical axial spondyloarthritis (axSpA) defined by chronic inflammatory back pain, progressive spinal stiffness, and frequent extra-articular manifestations such as acute anterior uveitis (21%\u201333%), inflammatory bowel disease (5%\u201310%), and psoriasis (4%\u201313%). Management has shifted from non-steroidal anti-inflammatory drugs (NSAIDs) to highly targeted biologic and synthetic disease-modifying antirheumatic drugs (DMARDs). This comprehensive review focuses on the current evidence for biologic and targeted synthetic therapeutics in the management of AS, emphasizing mechanisms of action, regulatory approvals, dosing regimens, and clinical efficacy. Three major therapeutic classes are identified: two biologic DMARD classes, comprising tumor necrosis factor-alpha (TNF-\u03b1) inhibitors and interleukin-17 (IL-17) inhibitors, and the targeted synthetic DMARDs, namely, the Janus kinase-signal transducer and activator of transcription (JAK-STAT) inhibitors. TNF inhibitors (adalimumab, infliximab, etanercept, golimumab, certolizumab pegol) typically achieve Assessment of Spondyloarthritis International Society 40% improvement (ASAS40) rates of 40%\u201358% at 12\u201324 weeks\n                    <jats:italic>versus<\/jats:italic>\n                    13%\u201324% with placebo, and maintain clinical benefit in many patients over 5\u20138 years. IL-17 inhibitors (secukinumab, ixekizumab, bimekizumab, brodalumab, netakimab) yield broadly similar ASAS40 responses (30%\u201350%\n                    <jats:italic>versus<\/jats:italic>\n                    10%\u201320% placebo) and are particularly useful in patients with concomitant psoriasis with substantially reduced risk of tuberculosis reactivation. JAK inhibitors (tofacitinib, upadacitinib) represent the newest class, offering oral administration with ASAS40 responses of 40%\u201352%\n                    <jats:italic>versus<\/jats:italic>\n                    13%\u201326% for placebo in both biologic-na\u00efve and biologic-experienced AS, though cardiovascular safety considerations necessitate careful patient selection. Therapeutic selection should consider comorbidities (uveitis favors TNF monoclonal antibodies; psoriasis favors IL-17 inhibitors), safety profile, route of administration, and sequencing after non-steroidal anti-inflammatory drug failure. Understanding these pharmacological distinctions enables personalized therapeutic decisions based on the specific molecular pathology and risk profile of the individual patient.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1865621","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:03:49Z","timestamp":1787724229000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Biologic and targeted synthetic therapies in ankylosing spondylitis: a pharmacological review"],"prefix":"10.3389","volume":"17","author":[{"given":"Omar Z.","family":"Ameer","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem","family":"Temsah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara O.","family":"Alsouss","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Public Health, College of Medicine, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghad","family":"Al-Amoudi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Northeastern University","place":["Toronto, ON, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Khanfar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim M.","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, College of Pharmacy, Alfaisal University","place":["Riyadh, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"631","DOI":"10.3390\/jcm11030631","article-title":"Risk of acute anterior Uveitis in ankylosing spondylitis according to the type of tumor necrosis factor-alpha inhibitor and history of Uveitis: a nationwide population-based study","volume":"11","author":"Ahn","year":"2022","journal-title":"J. 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