Reviews & Analysis

Results of the STEP 9 trial show that semaglutide leads to improvements in knee osteoarthritis-related symptoms. The findings support weight-management pharmacotherapies as a feasible option for management of knee osteoarthritis, but cost-effectiveness, risk of toxicity and likelihood of rebound must be considered.

Emerging research in intervertebral disc degeneration in 2024 highlights microbial, immune and inflammatory mechanisms that drive chronic low back pain. These insights pave the way for potential transformative therapies that address the root causes of intervertebral disc degeneration and could improve patient outcomes.

The updated 2023 EULAR recommendations for treatment of systemic sclerosis bring notable changes to recommendations for skin, peripheral vascular disease, interstitial lung disease and pulmonary arterial hypertension therapies, based on newer evidence. These updates provide the first glimmer of personalized patient management.

Here, we highlight three publications in 2024 that have advanced the field of molecular and immunological profiling, for the diagnosis, prognosis and treatment of patients with systemic autoimmune rheumatic diseases.

In this Review the author summarizes the current approaches for antigen-specific therapies in the treatment of autoimmune disease and highlights the challenges that need to be addressed for successful use of this therapeutic strategy.

The role of proteases in cartilage degradation and the development of osteoarthritis is undeniable. Despite over two decades of research on protease inhibitors, however, the transition from preclinical promise to clinical success remains elusive, underscoring the urgent need to critically appraise the challenges and limitations inherent in preclinical studies.

In this Review, Nigrovic and colleagues examine potential mechanisms underlying the paradoxical continuation of inflammation in arthritis, despite the increased numbers of regulatory T cells in inflamed joints, and discuss the implications for regulatory T cell-targeted therapeutic interventions in inflammatory arthritis.

The identification of shared molecular mechanisms across systemic inflammatory autoimmune diseases with overlapping clinical manifestations has prompted research into the underlying genetics that could be driving these manifestations; elucidating these genes could aid in the diagnosis, treatment and outcome prediction of these complex diseases.

This Review provides an update on the evidence for the three main hypotheses of HLA-B27 in the pathogenesis of spondyloarthritis. The authors discuss the current understanding of the effect of HLA-B27 on innate and adaptive immunity and how this drives disease.

This Review provides a comprehensive update on dysregulated type I interferon production and signalling in autoinflammatory interferonopathies, monogenic systemic lupus erythematosus and conditions that present with broad immune dysregulation and interferon signatures. The authors provide a classification for autoinflammatory interferonopathies based on disease mechanisms of increased type I interferon production and signalling and overlapping clinical phenotypes.

This Review provides an update on autoantibodies associated with idiopathic inflammatory myopathies in both adults and children. The authors also discuss methods of autoantibody detection and the advantages and limitations of each technique.

Studies published in 2024 suggest that although the repurposing of established rheumatology drugs seems to deliver incremental benefits for pain management, greater benefits could be gained in the future by targeting newly discovered pain mechanisms.

EULAR and the Paediatric Rheumatology European Society (PReS) now view systemic juvenile idiopathic arthritis and adult-onset Still’s disease as a single disease — Still’s disease — given their overlapping biomarkers, clinical manifestations and complications. This consensus provides valuable insights into Still’s disease diagnosis and management across age groups, and also highlights research priorities.

During the past year, four studies have reported ten mutations in UNC93B1, which encodes the Toll-like receptor (TLR) chaperone protein UNC93B1. All variants increased TLR7 and TLR8 signalling and caused systemic lupus erythematosus in young individuals, and highlight the therapeutic potential of targeting TLR7 and TLR8 in this disease.

BCR-independent memory B cell reactivation via TLR7 or TLR8 activation, type I interferon production, immune complex formation and T helper cell signalling is central in SLE pathogenesis. Dörner and Lipsky discuss the potential of targeting these pathways to eliminate autoreactive memory B cells and plasma cells in SLE.

This Review provides an overview of the pathogenesis, classification and diagnosis of and treatment strategies for adult and paediatric rheumatology patients with uveitis. The authors highlight the importance of collaborations between ophthalmologists and rheumatologists to provide optimal treatment of uveitis, improve patient care and enhance future research.

Digital health has the potential to improve patient care in rheumatology and alleviate strain on the health-care system. This Review explores the current status of the transition from traditional health care to a model that harnesses the potential of digital health technologies, including discussion of the main benefits and barriers.

In this Review, López and Gualillo discuss the complex interrelationships between rheumatic diseases and the hypothalamic and autonomic mechanisms that regulate metabolism, and explore the therapeutic potential of targeting central regulators of energy balance.

Despite the availability of numerous treatment options, the management of rheumatoid arthritis remains suboptimal. In this Review, Konzett and Aletaha discuss strategies to advance clinical decision-making from trial-and-error to an informed process that considers more than just drug efficacy, and appropriately balances effort and success.

This Review discusses the involvement of early-stage and late-stage somatic mutations in the pathogenesis of both monogenic and multifactorial rheumatic diseases. The authors highlight new methods of detecting low-frequency variants and the implications for diagnosis and treatment in patients with rheumatic diseases.