The identification of individuals with systemic sclerosis in an oligosymptomatic phase preceding the very early manifestations of the disease represents a challenge in the search for a new window of opportunity in systemic sclerosis. This phase could be identified in a clinical scenario as the pre-scleroderma phase, in which the disease would still be far from systemic sclerosis-related fibrotic or irreversible manifestations in skin or organs. In this Personal View, we discuss parameters and candidate definitions for a conceptual framework of pre-scleroderma, from the identification of populations at risk to autoantibodies and their potential functional activities. We discuss how this new paradigm of pre-scleroderma could represent a game-changing approach in the management of systemic sclerosis, allowing the treatment of patients at high risk of organ involvement or skin fibrosis before such events occur.

The phase 2b Riociguat Safety and Efficacy in Patients with Diffuse Cutaneous Systemic Sclerosis (RISE-SSc) trial investigated riociguat versus placebo in early diffuse cutaneous systemic sclerosis. The long-term extension evaluated safety and exploratory treatment effects for an additional year.

Despite highly effective targeted therapies for rheumatoid arthritis, about 40% of patients respond poorly, and predictive biomarkers for treatment choices are lacking. We did a biopsy-driven trial to compare the response to rituximab, etanercept, and tocilizumab in biologic-naive patients with rheumatoid arthritis stratified for synovial B cell status.

The association of female sex with certain rheumatic symptoms and diseases is now indisputable. Some of the most striking examples of this association occur in individuals with musculoskeletal pain and osteoarthritis, in whom sex-dependent changes in incidence and prevalence of disease are seen throughout the lifecourse. Joint and muscle pain are some of the most common symptoms of menopause, and there is increasingly compelling evidence that changes in or loss of sex hormones (be it natural, autoimmune, pharmacological, or surgical) influence musculoskeletal pain propensity and perhaps disease. However, the effects of modulation or replacement of sex hormones in this context are far less established, particularly whether these approaches could represent a preventative or therapeutic opportunity once symptoms have developed. In this Review, we present evidence for the association of changes in sex hormones with musculoskeletal pain and painful osteoarthritis, discussing data from diverse natural, therapeutic, and experimental settings in humans and relevant animal models relating to hormone loss or replacement and the consequent effects on health, pain, and disease. We also postulate mechanisms by which sex hormones could mediate these effects. Further research is needed; however, increased scientific understanding of this complex area could lead to real benefits in musculoskeletal and women's health.

Efficacy of combination therapy with methotrexate and biological disease-modifying antirheumatic drugs is well established in the management of patients with rheumatoid arthritis; however, the optimal dose of methotrexate to administer with a tumour necrosis factor inhibitor remains unclear. We aimed to clarify the efficacy and safety of adalimumab combined with reduced methotrexate dose compared with the maximum tolerated methotrexate dose in patients with rheumatoid arthritis and an inadequate response to methotrexate monotherapy.

Rituximab was effective for patients with polymyalgia rheumatica in the 21-week BRIDGE-PMR randomised controlled trial. Here, we aimed to assess rates of glucocorticoid-free remission up to 1 year after infusion in an extension of this trial.

Targeted biological immunotherapies have been highly effective in controlling skin disease in patients with psoriasis, but whether therapy delays progression to inflammatory arthritis is unclear. The aim of this study was to compare the time to incident inflammatory arthritis among patients newly receiving biological therapies for psoriasis.