ReviewCurrent opinion in rheumatology2026
Difficult-to-treat, complex-to-manage, treatment-refractory spondyloarthritis: semantics or substance?
Review in Current opinion in rheumatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Authors and funding
3 authors.
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Abstract
purpose of reviewThe concept of difficult-to-treat (D2T) disease is increasingly recognized across immune-mediated inflammatory diseases, and was recently introduced in spondyloarthritis (SpA). Several terms, including difficult-to-manage (D2M), complex-to-manage (C2M), and treatment-refractory (TR) describe disease states characterized by persistent symptoms and inadequate response to targeted therapies. This review aims to clarify the emerging constructs of D2M and TR disease in axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), and their implications for emerging research in this area. RECENT
findingsRecent initiatives from ASAS, EULAR, and GRAPPA have proposed definitions to frame D2T clinical scenarios in axSpA and PsA. These converge on distinguishing treatment-refractory disease, characterized by persistent objective inflammation despite multiple targeted therapies, from broader D2M/C2M states driven by multifactorial contributors including non-inflammatory factors. Emerging data suggest that clinical and biological heterogeneity across disease domains may contribute to these phenotypes. Challenging phenotypic presentations often display overlapping features between axSpA and PsA, supporting the concept of a continuum across the SpA spectrum. SUMMARY: Distinguishing TR disease from broader D2M/C2M states is essential for avoiding inappropriate treatment escalation, and supporting personalized multidisciplinary care. Further research is needed to validate these definitions, determine contributing factors and their prevalence, and clarify the molecular mechanisms underlying treatment refractory disease.
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