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Systematic reviews, although they can highlight important findings in the literature, often raise even more questions. In this Viewpoint, Prof Smolen and Prof Aletaha discuss approaches to comprehensive reviews in general, and to those involving rheumatoid arthritis in particular, from the clinical trialist's point of view.

Patient-derived functional measures such as the Health Assessment Questionnaire (HAQ) are important tools in the assessment of general health, function, and disability in patients with rheumatic diseases, such as rheumatoid arthritis. In this Viewpoint, Dr Aletaha and Dr Smolen discuss the use of these measures and their derivatives in predicting outcome in patients with rheumatic disease.

Targeted therapies and novel strategies to optimize their use enable many patients with RA to achieve a state of low disease activity or even remission, which can be maintained even after tapering or withdrawal of biologic DMARDs. In this article, Smolen and Aletaha review current concepts of RA treatment and the clinical evidence for their effectiveness, in the context of relevant issues such as factors influencing response to therapy, the 'window of opportunity' hypothesis and definitions of treatment targets.

Bone continuously undergoes building and degradation — a process known as bone remodelling. This tightly controlled process can be dysregulated by chronic inflammation, and bone loss is commonly associated with inflammatory diseases. Here, Redlich and Smolen discuss the molecular mechanisms mediating the inflammatory loss of bone and present strategies and agents for therapeutic intervention.

Rheumatoid arthritis is a chronic, inflammatory, autoimmune disease that primarily affects the joints. This Primer by Smolen et al. provides the latest insights into the epidemiology, genetics, pathophysiology, diagnostic approaches, clinical assessment and management of rheumatoid arthritis.

Choosing the correct management strategy for patients with rheumatoid arthritis in order to achieve the best possible outcome is a challenge to all rheumatologists. This Viewpoint considers current progress in the field of outcomes research in rheumatoid arthritis, along with future prospects of predicting individual patient response to therapy.

The concepts of comorbidity and multimorbidity consider a patient with multiple diseases from different perspectives, which affects how a clinician approaches treatment. In this Perspectives article, Radner and colleagues discuss the concept of multimorbidity and how its integration into daily clinical practice can improve the care of patients with rheumatic conditions.

For too long, the definition of ‘remission’ in rheumatoid arthritis has been distorted by the widespread use of an inadequate tool, with consequences for clinical care and for making sense of clinical trial data. Has the time come to move away from DAS28-defined remission?

Given a lack of head-to-head comparisons of the efficacy and safety of different biologic agents for the treatment of rheumatoid arthritis, can we instead compare systematic reviews that assess one agent at a time, or does heterogeneity between studies limit the usefulness of this approach?

Despite their different targets, biologic agents used for blockade of TNF and IL 6, inhibition of T cell co-stimulation and B cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. In this Perspective, the authors discuss the disparities in RA therapy and whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic RA cascade.

Comprehensive review articles written by international experts are important to provide readers from diverse backgrounds with an expanding knowledge base.

Optimizing COVID-19 vaccination strategies for patients under immunosuppressive medication is of high importance. In this clinical trial including non-seroconverted immunosuppressed patients, a homologous mRNA booster vaccination resulted in higher seroconversion rate than a switch to a vector-based vaccine.

The use of biologic therapies for off-label conditions in daily clinical practice is increasing, yet few studies have detailed the safety of these agents with regards to infection in patients with systemic autoimmune disease. New research offers a glimpse at the infection rates in these vulnerable patients.

Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.

Kurt Redlich and his colleagues show that estrogen deficiency results in increased numbers of preosteoclast progenitor cells in the bones of mice. But they also find that lack of CCR2 in these future bone-resorbing cells prevents their maturation and thus protects the mice from osteoporosis, suggesting a future target for therapy in humans.

From evidence pointing to a possible etiologic role for microbes to the development of new strategies and agents to treat early and established disease, 2010 has seen the publication of several interesting findings in the field of rheumatoid arthritis.

Circadian rhythms are well established as having an important role in human biology. In this Review, circadian biology is presented in reference to the regulation of rheumatoid arthritis and the potential for chronotherapeutic intervention.

The link between chronic inflammation and bone loss has been the subject of intense research over the past decade. This has led to the identification of key molecules that bridge the gap between immune function and bone turnover, including receptor activator of NFκB ligand, which represents a potential therapeutic target for patients with chronic inflammatory arthritis, and is the subject of this review.

A meta-analysis comparing primary efficacy outcomes of phase 2 and phase 3 randomized controlled trials in rheumatoid arthritis and psoriatic arthritis shows that phase 2 studies consistently overestimate the effect sizes anticipated in subsequent phase 3 trials.

In 2016, two international organizations published recommendations for the management of psoriatic arthritis. This article reviews the development of the recommendations, considers their similarities and differences, and provides guidance on how to interpret and apply the recommendations in practice.

Fibroblast-like synoviocytes (FLS) are major contributors to joint inflammation in rheumatoid arthritis (RA). Here, the authors identified a previously unknown signaling circuit that contributes to tumor necrosis factor (TNF)-induced activation of FLS. The authors show that FOXO3 and its modulator PIK3IP1 are crucial for the TNF-driven interferon (IFN) response in RA-FLS.