Year in Review

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.

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.

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.

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.

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 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.

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.

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.

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.

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.

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.

Although elegant work has detailed the clinical presentation, immune response and disease outcome of multisystem inflammatory syndrome in children, many questions remain. Studies in 2022 have explored the nature of the vascular injury, the role of the SARS-CoV-2 spike protein and the association with the current variants of the virus.

Successful, long-term treatment of articular cartilage injuries is important for the prevention of osteoarthritis but remains a major challenge. Three studies in 2022 highlight new approaches to improving articular cartilage regeneration.

Janus kinase inhibitors continue to show promise in a diverse range of indications, but administration of these drugs needs careful consideration of the benefits and risks. Among a plethora of publications in 2022, notable studies explored an important new indication and provided insights into safety concerns.

Electronic health records (EHRs) contain enormous amounts of real-world data that could inform researchers, doctors and patients about many aspects of rheumatology. However, EHRs are not yet fully utilized, mainly because automatic data extraction is difficult. Several studies in 2022 highlight the feasibility and clinical utility of computer-assisted EHR analysis.

In 2022, advances in the prediction of the response to treatment in rheumatoid arthritis resulted from gene-expression profiling in synovial biopsy samples, assessment of the expression of interferon-response genes in the blood, and the application of machine learning to patients’ clinical parameters and genetic variance.

Since the start of the SARS-CoV-2 vaccination campaign, our knowledge of the effects of vaccines in people with inflammatory rheumatic diseases has remained incomplete. In particular, the effects of immunomodulatory therapies on vaccine success are poorly understood. Three notable papers from the past year have helped to fill these knowledge gaps.

Interstitial lung disease (ILD) can arise in a variety of connective tissue diseases (CTDs) and various treatment interventions are being explored. In 2020, advances in the treatment of CTD-associated ILD have included the re-evaluation of methotrexate-induced lung injury and emerging insights on anti-IL-6 therapy and anti-fibrotic therapy in this condition.

Multisystem inflammatory syndrome in children (MIS-C) is a rare complication of SARS-CoV-2 infection that can result in serious illness in the paediatric population but our understanding of this syndrome is in its infancy. Translational studies in 2020 leveraging immune profiling have laid the foundation to enable further discovery in MIS-C.

Since the outset of the COVID-19 pandemic, numerous risk factors for severe disease have been identified. Whether patients with rheumatic diseases, especially those receiving DMARDs, are at an increased risk of SARS-CoV-2 infection or severe COVID-19 disease remains unclear, although epidemiological studies are providing some insight.