A platinum age for rheumatology

Abstract

On June 14–17, over 14 000 rheumatologists, health-care professionals, and patients will gather in Madrid, Spain, for the European League Against Rheumatism (EULAR) Annual Congress. 2017 is a particularly special year for the organisation as EULAR celebrates its 70th anniversary. Since our inception, The Lancet has been pleased to have shared in the rich history of rheumatology research, including The “Rheumatic Disease”, coauthored by the founding President of EULAR, Mathius Pierre Weil, in 1928 and today's issue, which highlights recent and innovative developments in therapeutics and management strategies for rheumatic diseases. Much of the recent knowledge of the underlying mechanisms that drive rheumatoid arthritis and other diseases has come from preclinical studies in cellular systems and animal models. Although important and essential research tools, these experimental systems do not always faithfully reflect human biology. In the first paper of a Series on targeted treatments for rheumatoid arthritis, Iain B McInnes and Georg Schett take a novel and refreshing approach to understanding the molecular pathogenesis of the disease in patients. They review findings from clinical trials of new biologics designed to target specific immunological pathways, and critically evaluate lessons learned from the success and failure of these studies. By doing so, McInnes and Schett provide a comprehensive overview of the roles of key cytokines, including tumour necrosis factor α, interleukin 6, and granulocyte–macrophage colony-stimulating factor. Insights gained from use of novel Janus kinase (JAK) inhibitors, which target pathway components downstream of cytokine receptors, are also discussed in the paper. JAK inhibitors tofacitinib and baricitinib are approved for treatment of arthritis and other rheumatoid diseases. Knowing which cytokine and signalling pathways to target in specific individuals is a huge advance, but for a complex, progressive, chronic disease such as rheumatoid arthritis, the timing of intervention is also critical. Around 25 years ago, the recommended treatment approach was slow and steady, referred to as “the pyramid”—ie, a base of physical therapy and non-pharmacological interventions, followed by conservative treatment with non-steroidal anti-inflammatory drugs, then glucocorticoid steroids and, finally, administration of a conventional disease-modifying antirheumatic drug (DMARD). Over the past decade or so, this concept has been inverted. Intensive intervention, initiated earlier, with conventional and biological DMARDs is increasingly recommended. Gerd R Burmester and Janet E Pope, in the second paper of the Series, discuss these evolving treatment strategies for rheumatoid arthritis. They emphasise the role of biologics and small molecule inhibitors in the therapeutic arsenal, and review accumulating evidence that supports an early window of opportunity for diagnosis, as well as management regimens, such as treat-to-target approaches that include rapid intervention, reassessment, and adjustment of medications for patients who do not achieve remission within 6 months—with the aim of preventing or slowing structural damage. Raising awareness of these new recommendations, this year, EULAR launched a new campaign, “Don't delay, connect today”, aimed at patients, general practitioners, and specialist rheumatologists alike. Patient involvement in research and clinical decision making is a cornerstone of EULAR, exemplified by People with Arthritis and Rheumatism (PARE), one of the pillars of the organisation. PARE works with researchers to ensure a patient-centred approach to care at all levels, and with patient advocacy groups to help to disseminate knowledge across Europe and to provide education to patients and their families. The rapid rate at which discoveries have emerged over the past two decades has brought about a revolution in treatment paradigms for rheumatoid arthritis. Many of these developments have occurred in parallel with or have helped to inform insights into management of a range of rheumatoid diseases, as well as other immunologically driven conditions. But the question of the feasibility of implementing early and intensive intervention with new biologics in settings other than high-income countries remains. The NOR-SWITCH study showed non-inferiority for switching from infliximab originator to a biosimilar in patients with rheumatoid arthritis, psoriatic arthritis, Crohn's disease, and other conditions for which infliximab is currently approved. Biosimilars might provide affordable options for treating rheumatism, but it remains to be seen how effectively the new treatment strategies can be implemented on a global scale. An unprecedented range of therapeutic options for rheumatic diseases is now available—the new challenge is to make them accessible. EULAR: Countries unite to fight rheumatic diseasesRetired grammar school teacher Dieter Wiek is neither a trained scientist nor a clinician, but his perspective as a patient helps set the research and treatment agenda for rheumatic diseases in Europe and beyond. Full-Text PDF Gerd Burmester: enduring leader in rheumatoid arthritisHaving been Professor of Medicine at Berlin's Charité University Clinic for the past 23 years, Gerd Burmester is among the university's longest-standing full professors. He leads a 100-strong Department of Rheumatology and Clinical Immunology, and is as committed to research in the laboratory as to work in the clinic. His team is collectively researching how to reprogramme the human immune system, with an emphasis on the molecular pathways that underpin autoimmunity across many diseases, but especially in rheumatoid arthritis (RA). Full-Text PDF Switching from originator infliximab to biosimilar CT-P13 compared with maintained treatment with originator infliximab (NOR-SWITCH): a 52-week, randomised, double-blind, non-inferiority trialThe NOR-SWITCH trial showed that switching from infliximab originator to CT-P13 was not inferior to continued treatment with infliximab originator according to a prespecified non-inferiority margin of 15%. The study was not powered to show non-inferiority in individual diseases. Full-Text PDF Pathogenetic insights from the treatment of rheumatoid arthritisRheumatoid arthritis is a chronic autoimmune disease that causes progressive articular damage, functional loss, and comorbidity. The development of effective biologics and small-molecule kinase inhibitors in the past two decades has substantially improved clinical outcomes. Just as understanding of pathogenesis has led in large part to the development of drugs, so have mode-of-action studies of these specific immune-targeted agents revealed which immune pathways drive articular inflammation and related comorbidities. Full-Text PDF Novel treatment strategies in rheumatoid arthritisNew treatment strategies have substantially changed the course of rheumatoid arthritis. Many patients can achieve remission if the disease is recognised early and is treated promptly and continuously; however, some individuals do not respond adequately to treatment. Rapid diagnosis and a treat-to-target approach with tight monitoring and control, can increase the likelihood of remission in patients with rheumatoid arthritis. In this Series paper, we describe new insights into the management of rheumatoid arthritis with targeted therapy approaches using classic and novel medications, and outline the potential effects of precision medicine in this challenging disease. Full-Text PDF