Difficult-to-Manage Axial Spondyloarthritis

Axial spondyloarthritis (axSpA) is a multifaceted disease with a wide range of manifestations and associated comorbidities. Despite an expanding arsenal of disease-modifying anti-rheumatic drugs (DMARDs) in the treatment landscape of axSpA, a substantial number of patients remains resistant to multiple therapeutic interventions, posing a clinical challenge. This resistance may originate from both inflammatory and non-inflammatory factors. The term "difficult-to-manage" (D2M) axSpA, which was recently proposed by the Assessment of Spondyloarthritis international Society (ASAS), indicates the persistence of symptoms and/or signs despite treatment with ≥2 different classes of biologic/targeted synthetic DMARDs and requires a variety of factors leading to inadequate treatment response. Meanwhile, the term "treatment refractory" disease, implying a frank biologically active inflammatory process, was also defined as a subtype of the D2M group. Literature in this field is restricted, while definitions applied are diverse and often used interchangeably. Medline/PubMed, Scopus, and Google Scholar databases were searched for relevant full-text articles. This short review overviews the current concept and evidence regarding D2M axSpA, including its definition, prevalence, and associated key factors. Furthermore, current management is discussed, and possible therapeutic strategies are suggested for this special subgroup of axSpA patients.