Reviews & Analysis

Leukocytes travel through many different tissues during their lifetime, being educated by the cells and environments they encounter. An increased understanding of this journey in the context of rheumatoid arthritis offers hope for the development of future therapies.

A variety of biologic DMARDs now exist for the treatment of rheumatoid arthritis, but we don’t really know how these drugs function in vivo. Can time-lapse intravital imaging distinguish the modes of action of DMARDs by comparing response to joint destruction in mouse models of arthritis?

Some patients with psoriatic arthritis are refractive to one biologic therapy but not to others, and a strategy for selecting the right therapy for each patient is needed. The findings of a new study highlight the potential benefit of stratifying patients by their immunophenotype to select the optimal biologic to use.

A growing body of evidence indicates that neutrophils and neutrophil extracellular traps (NETs) are involved in the progression of rheumatic diseases. This Review focuses on the role of NETs in systemic lupus erythematosus, vasculitis, rheumatoid arthritis and gout.

A new epidemiological study suggests that only half of patients with hyperuricaemia will go on to develop gout. If ‘the glass is only half-full’, then is hyperuricaemia the most important risk factor for the development of gout?

Poor medication adherence and depression interfere with the management of patients with systemic lupus erythematosus, especially adolescent and young adult patients. For patients for whom clinic visits and education programs fail to improve adherence, novel social media-based interventions are demonstrating the ability to increase patient agency, self-efficacy, and adherence.

As the diagnosis and management of systemic lupus erythematosus (SLE) can be challenging, reclassification of SLE on the basis of biomarker data provides novel insights. Definitions of antinuclear antibodies and attention to SMAARTT criteria (specificity – sensitivity, measurable, actionable, added value, realistic, titres, timely) are needed to translate these new analytical frameworks into real-time clinical use.

The largest study to date on the genetics of hip and knee osteoarthritis (OA) has yielded new associations with genes encoding a cytokine, a kinase and a transcriptional repressor, as well as genetic correlations with other diseases. Can these clues help to unravel details of the pathogenesis of OA?

The development of cartilage-penetrating therapies relies on an in-depth understanding of the biophysical properties of this complex tissue. In this Review, knowledge accumulated over 50 years is synthesized to reveal the key principles of solute transport in cartilage.

Vascular and obstetric antiphospholipid syndrome are associated with the same pathogenic antiphospholipid antibodies but differ with respect to their associated clinical manifestations. The expression and distribution of β2 glycoprotein I, the main target of antiphospholipid antibodies, might explain these differences.

Therapeutic application of cannabis remains controversial despite evidence of pain-relieving functions, particularly for rheumatic diseases. However, whether cannabis can also be used as an immunomodulatory therapeutic agent needs to be counterbalanced by risk assessment for adverse effects.

Endothelial dysfunction is thought to be an important contributor to the increased risk of cardiovascular diseases seen in patients with rheumatoid arthritis. Microvascular endothelial dysfunction could be a useful predictive marker of cardiovascular events in early rheumatoid arthritis.

Biomarkers are urgently needed to improve diagnosis and patient care in systemic sclerosis (SSc). Jimenez and colleagues discuss the current state of biomarkers for SSc and provide an update on how new biomarkers could make personalized medicine a reality.

Pain management can be a difficult problem for patients with rheumatoid arthritis (RA), some of whom can experience pain similar to that reported by patients with fibromyalgia. Now, advanced imaging techniques are revealing neurobiological alterations in patients with RA that mirror those seen in fibromyalgia, hinting at new treatment possibilities.

The success of intravenous immunoglobulin immunotherapy in autoimmune diseases has inspired the development of novel Fc-based therapeutics, in particular, multimerized polyvalent Fc molecules. A new study reports that a recombinant IgG1 Fc hexamer alleviates acute and chronic autoimmune diseases in mice.

The use of biomarkers for drug development, clinical investigation and management is fundamental to the success of molecular medicine. This Review discusses the framework for the development of biomarkers as drug development tools, including discovery, analytical validation, clinical qualification and utilization.

The application of new technologies including RNA sequencing and machine learning to the analysis of synovial tissue is yielding new insights into the pathology of rheumatoid arthritis, with potential implications for the clinical management of the disease.

In this Perspectives article, Roemer et al. argue that the time has come to use MRI, rather than radiography, as the primary imaging modality for defining eligibility criteria for clinical trials of potential disease-modifying osteoarthritis drugs (DMOADs).

Axial disease occurs in psoriatic arthritis (PsA) and ankylosing spondylitis, but questions remain over whether axial PsA is a distinct disease. In this Review, the authors address the current state of knowledge concerning axial PsA and propose a research agenda.

In this Review, the authors summarize the results of genetics studies that confirm the importance of modulating urate levels in gout pathophysiology, and discuss how these discoveries could be applied to the treatment of hyperuricaemia and gout.