Reviews & Analysis

Emerging data suggest that the frequency of long-term opioid use is high among individuals with rheumatic and musculoskeletal diseases, which is of concern given the risks of opioid misuse. But is long-term opioid use really that high or is the situation more complicated?

Placebo responses are prevalent in clinical trials for osteoarthritis, and they hinder the identification of effective new treatments. In this Review, Colloca and Neogi describe various aspects of the placebo phenomenon, and demonstrate how this knowledge can help to improve the design of clinical trials.

In this Review, the authors provide an overview of the therapeutic effects of uricases, outcomes related to gout and its comorbidities in clinical trials and challenges surrounding the use of uricases as potent urate-lowering therapy for the treatment of gout.

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.

New evidence demonstrates that myelopoiesis in the bone marrow is a critical event in inflammatory arthritis and is maintained by acquired memory in innate immune cells, which perpetuate inflammation and tissue destruction.

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.

Extracellular vesicles derived from mesenchymal stromal cells provide the therapeutic benefits of the parental cells with advantages relating to immunogenicity and ease of handling. This Review discusses the therapeutic potential of native and modified extracellular vesicles for the treatment of rheumatic diseases, focusing on osteoarthritis and rheumatoid arthritis.

Rheumatoid arthritis synovium contains phenotypically and functionally heterogeneous fibroblast-like synoviocytes. Cutting-edge analyses have now defined at least four distinct states of these cells related to their location in the synovium, epigenetic imprinting and the influence of microenvironment mediators.

The rise in the use of digital health-care technologies such as electronic patient-reported outcome measures enables a transformation of the traditional care model. In light of the increasing demand for rheumatologists, telehealth could enable more efficient usage of scarce face-to-face appointments.

The TNF–TNF receptor signalling network has pleiotropic effects that can both promote and protect against immune-mediated diseases. Modulation of this network through the use of TNF receptor-targeting biologic drugs holds promise for treating various diseases, including TNF inhibitor-refractory diseases.

Drug-free remission is a treatment goal in rheumatoid arthritis that can be achieved by tapering and discontinuation of biologic DMARDs. However, newly published real-world evidence suggests that DMARD discontinuation occurs less frequently than results of clinical trials suggest, so it is important to question what the ultimate goal of treatment should be.

The pathogenesis of juvenile dermatomyositis (JDM) is complex and various evidence implicate a role for type I interferons. Could the use of a bioengineered paediatric skeletal muscle model provide insight into this disease and have potential for high throughput testing of therapeutic agents?

In this Review the authors outline the evidence for how sleep disturbance and inflammation interact in a positive feedback spiral in rheumatoid arthritis, leading to further inflammation, pain and progression of disease activity.

The rarity of various forms of vasculitis, as well as other rheumatic diseases, presents difficulties in studying the genetics of these diseases as well as for evaluating treatments. Might new approaches, such as joint genetic analyses and drug repurposing, provide opportunities to learn more about these diseases and identify new therapies and serve as a basis for basket clinical trials?

Vaccines are important tools for protection against infectious diseases, particularly in patients undergoing immunosuppression (including DMARD therapy). This Review discusses the effects of DMARDs on vaccine immunogenicity, focusing on influenza and SARS-CoV-2 vaccines, and potential mechanisms underlying these effects.

In this Consensus Statement, the Treatment Response Measure for Systemic Lupus Erythematosus Consortium presents the initial outcomes of a project to develop a clinical outcome assessment that can contribute to the regulatory approval process for therapeutic agents via its incorporation in end points of clinical trials in systemic lupus erythematosus.

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.

The potential for the co-occurrence of spondyloarthritis and inflammatory bowel disease means that gastroenterologists must identify articular manifestations and rheumatologists must identify intestinal manifestations. This Review describes the progress in the treatment of patients with both spondyloarthritis and inflammatory bowel disease.

This Review provides an overview of the complement system and its role in a range of rheumatic and autoimmune diseases, and examines the rapidly expanding landscape of complement therapeutics in these settings, as well as prospects for improving their clinical use.

No drugs are yet approved for the treatment of primary Sjögren syndrome, despite a large number of clinical trials. Non-conventional approaches can help to identify novel therapeutic targets. Using a drug-repositioning transcriptomic approach, interferon has emerged once again as a major target for intervention in this disease process.