Are There Disease Endotypes in Axial Spondyloarthritis and How Would We Define Them?

Is axial spondyloarthritis (axSpA) one disease or does it comprise multiple types? If the latter, how do we define those types-through clinical or imaging features, HLA-B27 status, or by other immunologic features? Data comparing disease outcomes for individuals with nonradiographic vs radiographic axSpA, or for male vs female patients, demonstrate distinctions. So then, how should we define endotypes? Endotypes are known as the subtype of a health condition defined by a functional or pathophysiologic function. Here, we review the endotypes used for defining rheumatoid arthritis, asthma, and psoriatic arthritis. Taking the lessons learned from these diseases, we discuss how they can be applied to defining endotypes in axSpA. A key unmet need for axSpA is access to affected tissues for interrogation of their pathologic mechanisms, from which tissue-specific endotypes can be defined. These tissue-based features should be combined with clinical data and imaging to inform classification criteria in the future.