Shared challenges in the management of difficult-to-treat chronic inflammatory diseases: expert perspectives

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The concept of difficult-to-treat (D2T)/difficult-to-manage (DTM) disease was first defined in rheumatoid arthritis (RA). Recent definitions for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) combine non-response to treatment including targeted and biologic treatment, inflammatory disease activity, and patient symptoms. This concept could apply to other chronic inflammatory diseases such as psoriasis (PsO) and inflammatory bowel disease (IBD). A consensus definition of D2T IBD is available but is yet to be fully articulated in PsO. This article aims to provide an expert overview of the shared elements and potential differences between the definitions and concepts of D2T/D2M in these diseases. D2T/D2M definitions should allow better evaluation of refractory diseases, accurate determination of disease severity, and effective treatment of the D2T areas or domains. Definitions should consider response to previous lines of treatment, control of inflammation, and global disease improvement, and consider the impact of D2T disease on patient status/quality of life. Proof-of-concept studies need to assess the current and future definitions of D2T/D2M populations in axSpA, PsA, PsO, and IBD, to accurately determine the prevalence of patients meeting each of those D2T criteria sets, and to identify risk factors, disease burden, and appropriate management strategies. Difficult-to-treat (D2T) and difficult-to-manage (D2M) disease refers to a disease state where some symptoms persist, with or without detectable inflammation, despite treatment. Patients and physicians consider these diseases problematic to manage. Definitions of D2T/D2M diseases in rheumatic diseases include rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). These definitions are a combination of non-response to treatment (including targeted and biologic treatment), persistent inflammation, patient’s symptoms and dissatisfaction. Other inflammatory diseases are also appropriate for defining D2T/D2M states. These include inflammatory bowel disease (IBD) where a definition has recently been proposed, and psoriasis (PsO). Identifying patients with uncontrolled states of disease such as D2T/D2M states is important, because these diseases may continue to impact quality of life and progressively damage the organs. Clinicians need to be able to accurately define and recognize D2T/D2M states in each type of chronic inflammatory condition. This article provides an expert overview of the current existing definitions, and a discussion of what further information is needed so that physicians can accurately determine which patients fit into each D2T/D2M criteria, their risk factors and disease burden, to guide management strategies for these patients.