INTRODUCTION: This guideline offers evidence-based recommendations for physicians and policymakers on managing axial spondyloarthritis (axSpA) in Saudi Arabia. METHODS: A panel of 14 experts in research methodology, rheumatology, family medicine, and clinical pharmacology in Saudi Arabia approved 45 questions related to the monitoring and treatment, pharmacological and non-pharmacological, of different subtypes of axSpA. We conducted a search of different databases, including PubMed, EMBASE, and the Cochrane Library, from 2010 to 2024 to identify systematic reviews, meta-analyses, and clinical studies related to the diagnosis and management of axSpA. To evaluate the certainty of the evidence and formulate recommendations, we employed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. The expert panel voted electronically on each recommendation. A recommendation was finalized when over 70% of the voting panel agreed. RESULTS: We issued 31 evidence-based recommendations and seven statements based on the experts' opinions, which are grouped into nine categories. This guideline recommends initiating non-steroidal anti-inflammatory drugs (NSAIDs) as the first-line therapy for patients with symptomatic axSpA. If NSAIDs are ineffective, second-line treatments such as tumor necrosis factor inhibitors (TNFis), interleukin-17 inhibitors (IL-17is), or Janus kinase inhibitors (JAKis) should be considered. Localized glucocorticoid injections are suggested as supplementary therapy for cases of isolated sacroiliitis, enthesitis, or peripheral monoarthritis not responding adequately to the treatment options. CONCLUSION: The Saudi clinical practice guidelines provide updated evidence-based recommendations for monitoring and treating adults with axSpA. These recommendations help guide the best practice for healthcare professionals in managing patients with axSpA in Saudi Arabia. https://link.springer.com/article/10.1007/s40744-025-00779-1

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