The term spondyloarthritis refers to a spectrum of inflammatory diseases, including axial spondyloarthritis and psoriatic arthritis, in which musculoskeletal and extra-musculoskeletal manifestations coexist. Targeted therapies have improved outcomes, yet many patients achieve only a partial response and sustained remission remains uncommon, irrespective of the drug mode of action used. Observations of repeated treatment failures have given rise to the concepts of difficult-to-manage and treatment-refractory disease, but non-response itself is inconsistently defined and is often treated as a single phenomenon. However, treatment non-response is a heterogeneous construct that needs to be unravelled by first differentiating apparent from true non-response. Four distinct clinical patterns of true non-response can be identified — primary non-response, secondary loss of response, divergent responses across disease domains and paradoxical reactions — shaped to differing extents by drug exposure, dependence on the targeted pathway and anatomical compartmentalization. Recognizing these patterns and likely mechanistic underpinnings could support more rational treatment selection, limit unnecessary switching of targeted therapies and inform future biomarker-driven strategies to anticipate and ultimately prevent non-response. Treatment non-response in spondyloarthritis is heterogeneous rather than a single phenomenon. This Review proposes a framework that distinguishes primary, secondary, divergent non-response and paradoxical reaction, and highlights how separating true from apparent treatment failure could inform more precise therapeutic strategies.
Sjögren disease (SjD) is a common and chronic autoimmune systemic disease characterized by dryness, fatigue, pain and possible organ dysfunction. Understanding of SjD remains largely centred on the salivary glands, given that approximately 90% of patients report xerostomia and the glands are routinely sampled for diagnosis. However, SjD is a highly heterogeneous disease, and most patients present with systemic (extra-glandular) involvement at diagnosis, including interstitial lung disease, arthritis and renal disease. T cells seem central to the development of organ-specific disease, whereas B cells are pivotal to autoantibody production and lymphomagenesis. Several areas of uncertainty remain, including why certain organs are targeted by inflammation, understanding the disconnect between symptoms and pathology, and whether targeting the T cell-predominant infiltrate might have therapeutic benefit. Therefore, the pathogenesis of SjD might be best explained as a continuum of inflammation extending from the glands to distant target organs. A deeper understanding of SjD pathogenesis will be instrumental in the development of targeted therapies in organ-threatening disease. The authors of this Review provide a comprehensive overview of the pathogenesis of the systemic manifestations of Sjögren disease (SjD). They challenge the traditional view of SjD as comprising distinct glandular and extra-glandular manifestations and instead present the disease as a continuum of inflammation extending from the salivary glands to distant target organs.
The treatment of systemic lupus erythematosus has evolved rapidly over the past decade, particularly in lupus nephritis and in the musculoskeletal and cutaneous domains. These advances are especially relevant in Latin America, where patients face unique challenges related to health care access and resource availability. These evidence-based Latin American Group for the Study of Lupus–Pan-American League of Associations for Rheumatology guidelines provide an update of the 2018 recommendations, incorporating newly approved therapies and new evidence from randomized controlled trials into organ-based treatment algorithms that support earlier integration of biologic drugs when appropriate. The recommendations are complemented by overarching good-practice statements. The recommendations support individualized management according to organ involvement and disease severity, promoting earlier therapeutic optimization, including biologic drugs and targeted therapies when appropriate, the selective use of combination therapies and strategies to minimize glucocorticoid exposure. These updated guidelines reinforce a treat-to-target strategy in which remission or low disease activity are the primary therapeutic goals, and sustained remission represents the optimal long-term outcome. The recommendations also emphasize the need to implement evidence-based care within the realities of Latin American health care systems, where variability in access to treatment and health care resources might influence treatment. These Evidence-Based Guidelines update the 2018 Latin American Group for the Study of Lupus–Pan-American League of Associations for Rheumatology recommendations for the treatment of systemic lupus erythematosus in Latin America. The guidelines address regional challenges, while providing an organ-based framework that integrates evidence from randomized controlled trials and newly approved therapies.
In the MAINRITSEG clinical trial, treatment with rituximab did not confer an advantage over azathioprine for the maintenance of remission in patients with eosinophilic granulomatosis with polyangiitis.
In patients with active Sjögren disease, treatment with ianalumab 300 mg monthly reduced disease activity, but not symptom scores, more than placebo in two phase III clinical trials.
