Biomarkers for diagnosis, monitoring of progression, and treatment responses in ankylosing spondylitis and axial spondyloarthritis

John D. Reveille

With the growing awareness of the impact of chronic back pain and axial spondyloarthritis and recent breakthroughs in genetics and the development of novel treatments which may impact best on early disease, the need for markers that can facilitate early diagnosis and profiling those individuals at the highest risk for a bad outcome has never been greater. The genetic basis of ankylosing spondylitis has been considerably advanced, and HLA-B27 testing has a role in the diagnosis. Knowledge is still incomplete of the rest of the genetic contribution to disease susceptibility, and it is likely premature to use extensive genetic testing (other than HLA-B27) for diagnosis. Serum and plasma biomarkers have been examined extensively in assessing disease activity, treatment response, and as predictors or radiographic severity. For assessing disease activity, other than C-reactive protein and erythrocyte sedimentation rate, the most work has been in examining cytokines (particularly interleukin 17 and 23), matrix metalloproteinase (MMP) markers (particularly MMP3). For assessing those at the highest risk for radiographic progression, biomarkers of bony metabolism, cartilage and connective tissue degradation products, and adipokines have been most extensively assessed. The problem is that no individual biomarkers has been reproducibly shown to assess disease activity or predict outcome, and this area still remains an unmet need, of relevance to industry stakeholders, to regulatory bodies, to the healthcare system, to academic investigators, and finally to patients and providers.