Key Advances in Rheumatology

Advances in artificial intelligence (AI) are transforming patient stratification in rheumatology. In 2025, three landmark studies demonstrated how multimodal AI approaches spanning clinical, molecular and longitudinal data can uncover distinct disease subtypes and predict therapeutic response, advancing the field towards precision rheumatology.

In 2025, a new wave of ‘off-the-shelf’ B cell-depleting modalities for the treatment of autoimmune diseases emerged, encompassing allogeneic cellular therapies, in vivo chimeric antigen receptor engineering, and bispecific antibodies.

Many of the current therapies for arthritis lack a targeted approach, limiting clinical benefits. Nanoparticle-based delivery systems have enabled more precise and efficient delivery of therapeutic agents, particularly nucleic acids. Studies in 2025 emphasize the promise of these strategies for the treatment of various forms of arthritis.

New research published in 2025 sheds light on the pre-clinical period that precedes the onset of classifiable rheumatoid arthritis, from risk factors to immunological events and opportunities to prevent the transition to clinical disease.

Advances in cellular and spatial profiling technologies have rapidly expanded the understanding of fibroblast heterogeneity within the target tissues of disease. In 2025, there has been a shift towards a consensus definition of shared cross-tissue fibroblast states and a greater understanding of their molecular drivers and disease-relevant effector functions.

Fibromyalgia remains a challenge for researchers and clinicians. Three studies published in 2025 shed light on mechanisms and management by implicating gut microbiota in symptom perpetuation, demonstrating the potential of home-based neuromodulation, and examining the uncertain role of low-dose naltrexone.

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.

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.

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.

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.

In 2024, studies using more advanced methods to calculate the minimal important change have described how different methods and timings of estimating minimal important changes can affect the estimates.

Advances in gene, protein and cellular engineering provide unprecedented opportunities to redirect immune cells to treat autoimmunity. In 2023, novel cellular and precision immunotherapies showed remarkable promise in the treatment of rheumatic diseases.

Studies in 2023 have described eight new monogenic autoinflammatory diseases and their accompanying disease-causing mutations, uncovering clinical phenotypes, pathogenic mechanisms and therapeutic targets. Researchers have identified autoinflammatory pathways linked to mitochondrial dysfunction or overactivation of SRC family kinases.

For individuals with gout, the treatment options beyond conventional urate-lowering therapies are expanding. Notable advancements in 2023 include developments in uricase therapy, new xanthine oxidase inhibitors, and a class of medications that offer dual benefits for the control of type 2 diabetes mellitus and gout.

In 2023, large language models demonstrated potential for use in rheumatology to accurately suggest diagnoses and provide empathetic patient education. However, the propensity of this technology to generate misleading information continues to pose risks. Balancing innovation with physician guidance is essential.

Research published in 2023 has demonstrated the efficacy of sarilumab for IL-6 blockade in polymyalgia rheumatica and of secukinumab for IL-17 blockade in giant cell arteritis (GCA). Furthermore, preliminary results with human monocyte-derived suppressive cells suggest the potential of cellular therapeutics for the treatment of GCA.

Studies published in 2023 emphasize the long-term efficacy and safety of novel therapeutics for both radiographic and non-radiographic axial spondyloarthritis (axSpA) and provide a consensus definition of ‘early axSpA’ for use in research studies.

Generative artificial intelligence promises to reshape clinical care in rheumatology by supporting diagnostic reasoning, treatment planning and patient communication. Yet its potential rests on careful validation, transparent integration and thoughtful collaboration that strengthens, rather than substitutes, the human expertise central to patient care.

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.

Immunoengineering involves the design of materials with specific properties relating to the immune system. In this Review the authors consider the application of immunoengineering to systemic autoimmune diseases via site-specific and antigen-specific immunoregulation, the facilitation of immune cell therapy, novel approaches to immunodiagnostics and the generation of models to study autoimmunity.

This Review explores the potential of emerging RNA-based technologies and cell-engineering strategies, including those that incorporate small interfering RNA, microRNA, mRNA and synthetic receptor-mediated gene editing, to provide innovative and targeted approaches to osteoarthritis therapy.

CAR T cell therapy shows promise for achieving long-term drug-free remission in various autoimmune diseases. This Review discusses the ongoing challenges and unanswered questions of CAR T cell therapy in autoimmune diseases, including pre-procedural, procedural and post-procedural considerations.

This Review summarizes lessons learned from the use of rituximab in patients with systemic lupus erythematosus, and discusses the future of B cell targeting therapies, highlighting therapeutic options after rituximab failure and opportunities for personalized treatment.

Holers and colleagues review current data linking immune mechanisms and dysbiosis at distinct mucosal sites to risk of rheumatoid arthritis (RA). Their newly introduced causal mucosal endotypes hypothesis suggests that lung-, gut-, or oral-associated endotypes might drive the pathogenesis and progression of RA, and highlights associated research directions towards preventive and therapeutic strategies in RA.

Treatment of patients with arthralgia during the ‘window of opportunity’ could prevent disease development or a severe disease course. This Review summarizes available information on the completed and ongoing prevention trials in rheumatoid arthritis, including patient preferences and future considerations.

This Review provides a comprehensive overview of fibroblast biology in rheumatoid arthritis and other chronic inflammatory diseases. The authors discuss insights into fibroblast behaviour and pathogenicity from single-cell and functional studies and describe how these findings have informed efforts to therapeutically target fibroblasts.

In this Review article, the potential of cytometry- and single-cell RNA sequencing-based immune profiling for aiding the diagnosis and personalized treatment of rheumatic diseases is discussed.

In this Perspective, the authors propose a model in which an imbalance of threat and soothing systems leads to hyperactivation of the brain’s salience network, which, in conjunction with other mechanisms, contributes to fibromyalgia.

In systemic lupus erythematosus (SLE), pain is one of the most commonly reported and debilitating symptoms. The authors of this Review highlight the importance of understanding the mechanisms of pain in SLE and addressing pain and pain-associated symptoms in the management of SLE.