Reviews & Analysis

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.

A working group including authors of the latest OARSI and ESCEO recommendations for the management of knee osteoarthritis and independent experts compare and contrast these guidelines, and provide insights into their differences that could help inform application of the recommendations.

In this article, the authors discuss how the use of innovative clinical trial designs could facilitate the efficient evaluation of new and existing drugs in specific subgroups of patients, in order to optimize therapy allocation and address unmet clinical needs.

A subset of patients with coronavirus disease 19 (COVID-19) develop a thrombotic disorder that resembles a virally induced, complement-mediated thrombotic microangiopathy. Here, the authors present the theory and evidence for this disease model and discuss important considerations for treatment.

This Perspective article explores similarities in the inflammatory processes underlying coronavirus disease 2019 (COVID-19) and rheumatoid arthritis, including the role of pro-inflammatory cytokines and the potential of anti-cytokine therapies to treat COVID-19, as well as the effect of the COVID-19 pandemic on rheumatology.

In this Perspective article, the authors recount the earliest stages of translational research into IL-6 biology and the subsequent development of therapeutic IL-6 pathway inhibitors for the treatment of autoimmune rheumatic diseases and potentially numerous other indications.

Glucocorticoids have been used to treat patients with rheumatic diseases for more than 70 years, but have been controversial owing to their safety record. Are we now entering an age when opinions about their use in rheumatology clinics are converging?