Reviews & Analysis

Cell metabolism has long been at the forefront of tumour biology, but in the past decade the importance of cellular bioenergetics has been increasingly recognized in regulating immune cell function. Mechanistic studies in 2018 have highlighted cell metabolism as a potential therapeutic target for the treatment of rheumatoid arthritis.

In 2018, advances in the treatment of gout flares came in the form of a new nurse-led management approach to serum urate lowering and evidence that allopurinol might have a better cardiovascular safety profile than febuxostat. However, are IL-1β blockers such as canakinumab the future of care for patients with gout?

Nakazawa and colleagues describe advances in our understanding of anti-neutrophil cytoplasmic antibody-associated vasculitis. These insights have already generated promising new treatments that target B cells, T cells and cytokines; potential novel approaches targeting additional cells or molecules are also discussed.

The treatment of systemic lupus erythematosus involves a balance between control of disease activity and prevention of therapeutic harm that requires careful optimization. In this Review, the authors discuss available and emerging therapeutic strategies that exploit the current drug armamentarium.

Vitamin D is important for skeletal metabolism and calcium homeostasis, but conflicting evidence exists as to whether vitamin D supplementation has a protective effect on musculoskeletal outcomes. Do the results of a new meta-analysis bring clarity or increase confusion?

Shifts in cellular metabolism are central to activation, differentiation and proliferation of inflammatory cells and can contribute to the pathogenesis of inflammatory diseases. Integrating metabolomics data with other omics data is a major challenge but might enable clinicians to stratify stages of disease and response to therapy in patients with rheumatoid arthritis.

In osteoarthritis, identifying those patients at most risk of disease progression and/or who might benefit the most from therapy is an important step. Incorporating machine-learning into the development of prediction models has great potential for moving towards precision medicine

Gene therapy and tissue engineering strategies for the treatment of cartilage repair each pose unique challenges to clinical translation. Could combining the two approaches open new avenues for the treatment of articular cartilage defects in patients with osteoarthritis?

‘Patient-centered’ research has traditionally meant that researchers and clinicians design trials for the benefit of patients. By contrast, patients today are central to study design and reporting outcomes, and new research agendas recognize that patients can point the way to research questions and how to address them.

Intra-articular therapies for knee osteoarthritis (OA) are causing excitement among clinicians and patients, but care should be taken when choosing which therapy to use. In this Review, Vangsness and colleagues critically appraise current and future intra-articular therapies for knee OA.

Despite the previous identification of genes involved in the treatment response to TNF inhibition in rheumatoid arthritis, no genetic biomarkers are currently used in clinical decision-making. Might the heterogeneous nature of the disease activity score, which is often used as the outcome measure in genetic studies, partly explain this gap?

The search for the identity of skeletal stem cells has reached a point at which skeletogenic cell populations with self-renewing capacity can be enriched and studied in detail. These advances provide new hope for skeletal regenerative medicine.

Gasdermin D is a pore-forming protein that can cause pyroptosis, a form of inflammatory cell death. New research indicates that the pores generated by gasdermin D can also promote the formation of neutrophil extracellular traps, potentially opening new therapeutic avenues for the treatment of inflammatory diseases.

Stromal cells of mesenchymal origin can help to sustain inflammation in the joint by various mechanisms; understanding these mechanisms could inform new therapeutic strategies and explain why joint inflammation persists in diseases of the joint such as arthritis, enthesopathy and tendinopathy.

Hydroxychloroquine is a front-line treatment for systemic lupus erythematosus and other rheumatic diseases, but can cause retinopathy. Improved detection techniques for the early stages (pre-symptomatic) of retinopathy has led to recommendations for reduced dosing, but more data on the efficacy of low-dose hydroxychloroquine are needed.

Nocebo effects can occur in patients with rheumatic and/or musculoskeletal diseases, and might result in suboptimal treatment outcomes or non-adherence. The consideration of nocebos is important in rheumatology practice and clinical trial design, including when switching patients to biosimilars.

The ability to resolve, rather than suppress, inflammation could enable new possibilities for the treatment of chronic diseases such as rheumatoid arthritis. Knowing more about the function of immune-regulatory cytokines is the first step towards realizing their therapeutic potential.

A variety of comorbidities of gout exist, but most of these associations are not causally linked. Mendelian randomization analysis of genome-wide association study data now suggests that iron overload might increase serum uric acid levels and hence the risk of gout flares.

Our ability to interrogate the genetic and epigenetic processes that underpin disease are advancing rapidly. In this Review, Radstake and colleagues highlight insights gained into the pathogenesis of systemic sclerosis from the past 4 years of genetic and epigenetic research.

Hand osteoarthritis (OA) is a heterogeneous and prevalent condition involving multiple joints. In this Review, the authors provide an update on the epidemiology, presentation and burden of hand OA, as well as on advances in imaging techniques, disease management and pathogenesis.