Biomarker development for axial spondyloarthritis

The term axial spondyloarthritis (axSpA) encompasses a heterogeneous group of diseases that have variable presentations, extra-articular manifestations and clinical outcomes, and that will respond differently to treatments. The prototypical type of axSpA, ankylosing spondylitis, is thought to be caused by interaction between the genetically primed host immune system and gut microbiota. Currently used biomarkers such as HLA-B27 status, C-reactive protein and erythrocyte sedimentation rate have, at best, moderate diagnostic and predictive value. Improved biomarkers are needed for axSpA to assist with early diagnosis and to better predict treatment responses and long-term outcomes. Advances in a range of ‘omics’ technologies and statistical approaches, including genomics approaches (such as polygenic risk scores), microbiome profiling and, potentially, transcriptomic, proteomic and metabolomic profiling, are making it possible for more informative biomarker sets to be developed for use in such clinical applications. Future developments in this field will probably involve combinations of biomarkers that require novel statistical approaches to analyse and to produce easy to interpret metrics for clinical application. Large publicly available datasets from well-characterized case–cohort studies that use extensive biological sampling, particularly focusing on early disease and responses to medications, are required to establish successful biomarker discovery and validation programmes. Biomarkers help in the diagnosis and monitoring of disease, but robust biomarkers can be difficult to discover and validate. This Review explores the state of biomarker discovery for axial spondyloarthritis and suggests future developments to advance this field. Key points Genomic and proteomic biomarkers in current clinical use for axial spondyloarthritis (axSpA) perform moderately well but there is a great need for more informative biomarkers. Polygenic risk scores capture a greater proportion of the genetic component of risk of ankylosing spondylitis and perform better than HLA-B27 testing for the diagnosis of this disease. Multiomic biomarkers are an underexplored area in axSpA that have the potential to be more informative than individual biomarkers. Future biomarker development requires the availability of biological samples from large, well-characterized patient cohorts and datasets. Biomarker development programmes should be an integral component of clinical trials, and biom