Beyond the horizon: Innovations and future directions in axial-spondyloarthritis

Abstract

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease of the spine and sacroiliac joints. This review discusses recent advances across multiple scientific fields that promise to transform axSpA management. Traditionally, axSpA was considered an immune-mediated disease driven by human leukocyte antigen B27 (HLA-B27), interleukin (IL)-23/IL-17 signaling, biomechanics, and dysbiosis. Diagnosis relies on clinical features, laboratory tests, and imaging, particularly magnetic resonance imaging (MRI) nowadays. Management includes exercise, lifestyle changes, non-steroidal anti-inflammatory drugs and if this is not sufficient to achieve disease control also biological and targeted-synthetic disease modifying anti-rheumatic drugs. Beyond long-recognized genetic risks like HLA-B27, high-throughput sequencing has revealed intricate gene-environment interactions influencing dysbiosis, immune dysfunction, and aberrant bone remodeling. Elucidating these mechanisms promises screening approaches to enable early intervention. Advanced imaging is revolutionizing the assessment of axSpA's hallmark: sacroiliac bone-marrow edema indicating inflammation. Novel magnetic resonance imaging (MRI) techniques sensitively quantify disease activity, while machine learning automates complex analysis to improve diagnostic accuracy and monitoring. Hybrid imaging like synthetic MRI/computed tomography (CT) visualizes structural damage with new clarity. Meanwhile, microbiome analysis has uncovered gut ecosystem alterations that may initiate joint inflammation through HLA-B27 misfolding or immune subversion. Correcting dysbiosis represents an enticing treatment target. Moving forward, emerging techniques must augment patient care. Incorporating patient perspectives will be key to ensure innovations like genetics, microbiome, and imaging biomarkers translate into improved mobility, reduced pain, and increased quality of life. By integrating cutting-edge, multidisciplinary science with patients' lived experience, researchers can unlock the full potential of new technologies to deliver transformative outcomes. The future is bright for precision diagnosis, tightly controlled treatment, and even prevention of axSpA.

Keywords: Artificial intelligence; axial spondyloarthritis; future directions; imaging; innate immunity..

Figure 1. Spondyloarthritis spectrum from axial to peripheral involvement. SpA: Spondyloarthritis; IBD: Inflammatory bowel disease. Modified from Proft F et al. Ther Adv Musculoskelet Dis 2018;10:129-39.

Figure 2. New frontiers in axSpA. An overview of emerging areas of research. Key areas highlighted include immunology, genetics, microbiome studies, imaging techniques, and artificial intelligence. Specific examples in each domain are listed. This illustrates the range of innovative techniques being applied to gain new insights into axSpA. HLA-B27: Human leukocyte antigen B27; ILCs: Innate lymphoid cells; MAIT: Mucosal-associated invariant T; CT: Computed tomography; MRI: Magnetic resonance imaging; LLM: Large language model; axSpA: Axial spondyloarthritis.