Perspectives

This Perspective article discusses the stratification of patients with knee osteoarthritis (OA) in the context of current guidelines, biomarkers and emerging and future developments of targeted treatment. The authors aim to highlight how these novel developments can enhance the stratification of patients with knee OA to improve patient outcomes.

Delays in the diagnosis of systemic lupus erythematosus negatively affect the treatment, quality of life and outcomes of affected individuals. In this Perspective, the authors provide an overview of the contributing factors and consequences of diagnostic delay in systemic lupus erythematosus and discuss how this urgent issue should be addressed.

In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.

In this Perspective, the authors propose that patients with psoriatic arthritis and an inadequate response to therapy can be classified into two distinct subgroups, characterized by persistent inflammatory and non-inflammatory phenotypes, and discuss potential mechanisms underlying these phenotypes, as well as considerations for treatment strategies and trial design.

The diagnosis, treatment and management of systemic sclerosis (SSc) remains challenging, owing to the complexity of this disease. In this Perspective, an international group of experts discuss the future of SSc research and how the advent of innovative technologies will advance research into and understanding of SSc.

Paediatric rheumatology has seen many notable developments in the past 25 years, including the introduction of the concept of autoinflammation and a greater understanding of the genetics and pathogenesis of inflammatory diseases. In this Perspective, Ozen and Aksentijevich discuss how these and other discoveries have transformed the field and herald improvements in patient care.

Beyond the traditional classification of monogenic or complex, many genetic diseases can be considered genetically transitional disease. In this Perspective, the authors consider the application of the genetically transitional disease model to rheumatic diseases and the potential implications for patient care, genetic counselling and research.

In this Perspective, the authors propose that despite the known similarities between ankylosing spondylitis and axial psoriatic arthritis, the localization of inflammation to bone in ankylosing spondylitis and to ligamentous soft tissue in axial axial psoriatic arthritis differentiates these diseases and has important implications for diagnosis, pathology and treatment.

In this Perspective, the authors discuss select examples of advancements in high-resolution imaging, functional molecular imaging and artificial intelligence-based analysis that hold promise for addressing current imaging limitations, enabling earlier diagnosis, improved monitoring and ultimately, personalized patient management.

Similarities in the pathogenesis and treatment of immune-mediated inflammatory diseases suggest that they can be investigated together in basket trials, to reduce the risk of failure of early-phase drug development and to facilitate the study of rare diseases.

In this Perspective, the authors discuss molecular, cellular and imaging evidence in spondyloarthritis that supports a bone marrow rather than an entheseal origin. Focusing on immune cells and dysfunction in the bone marrow niche could redirect the therapeutic approach to spondyloarthritis.

Long-term treatment with the anti-resorptive drug denosumab results in a continuous gain in bone mineral density, whereas denosumab withdrawal results in a transient overshoot in bone turnover, with rapid bone loss. This Perspective explores the potential mechanisms underlying these effects.

Next-generation sequencing has led to the discovery of multiple rare autoinflammatory diseases, together with their corresponding disease-causing mutations, creating opportunities to develop personalized medicine and providing useful insight into more common forms of autoimmunity and autoinflammation.

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 this Perspective, with specific reference to rheumatoid arthritis, Lin, Cooles and Isaacs identify factors that have contributed to the relatively slow progress towards precision medicine for rheumatic diseases, and suggest strategies for closing this ‘precision gap’.

The paradoxical increase in gout flare risk upon initiation of urate-lowering therapy presents challenges for the measurement and analysis of gout flares in clinical trials of urate-lowering therapy. In this Perspective, the authors highlight these issues and discuss potential solutions.

Here, the authors propose that more stringent MRI definitions for inflammatory and structural lesions in the sacroiliac joints should be used in randomized controlled trials in non-radiographic axial spondyloarthritis. They argue that such an approach might enhance diagnostic accuracy and thereby increase discrimination between therapies.

In this Perspective article, the authors discuss the results of the post-marketing ORAL Surveillance study comparing the safety of the JAK inhibitor tofacitinib and TNF inhibition in patients with rheumatoid arthritis, as well as the potential implications for clinical practice.

In this Perspective article, members of the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases discuss clinical and organizational challenges in this community caused by the COVID-19 pandemic and what lessons might be learned for the future.

In this article, the authors critically appraise the current model of opinion-based academia–industry interactions, and advocate for a realignment towards partnerships that foster innovation and knowledge.