Vivianne Malmström

Purpose and aims: To enable prevention of RA, both by providing information for public health based prevention and for precision prevention directed towards individuals at high risk for RA, and to improve outcomes for people who develop RA despite efforts towards prevention.More specific aims are to:better understand the role of environmental, genetic and immune determinants behind development of RAdevelop better diagnostic and surveillance tools to enable identification of individuals at high risk for RA (pre-RA)obtain new understanding of determinants and mechanisms for the protection against arthritis that is observed in some pre-RA individualsdevelop and evaluate digital tools that can provide patients and health care with information and capacity to test and implement precision prevention and early precision-based therapies for RA.Work planUse our large case-control and cohort studies to describe combinations of environment/life styles and genes that predict development vs protection of RAUse insights from (1) to determine which biomarkers that predict onset vs protection of RAUse novel digital tools to extend prospective cohorts of individuals at risk for RA, where prediction tools can be validated and mechanisms behind protection investigatedDevelop systems where precision prevention strategies can be tested and implemented.The long term clinical significance should be a shift in the care of RA from the present care of established disease to personalized prevention.

Immune checkpoints are designed to turn off the immune response to prevent autoimmunity and damage to healthy cells, but cancer hijacks these mechanisms by “deactivating” T cells that target cancer cells. Immunological checkpoint inhibitors (ICIs) prevent this deactivation and increase the body’s anti-tumour immune response. Immunotherapy with ICIs has revolutionized cancer treatment during the last years. Despite their high efficacy, ICIs are associated with a new spectrum of adverse events, referred to as immune-related adverse events (irAEs).Arthritis is a common irAE occuring in 7-10% of patients treated with ICI. It is a new rheumatic entity, that differs significantly from other forms of arthritis, in terms of clinical phenotype, pathogenesis and treatment. Current treatment guidelines support cortisone as first line therapy. However, preclinical data suggest that cortisone might reduce the effectiveness of cancer immunotherapy. On the contrary, targeted blockade of pro-inflammatory cytokines such as IL-6 might have excellent anti-inflammatory effect and at the same time not only not interfere with the effectiveness of the ICI but potentially even enhace it. That could support a paradigm shift in the treatment of irAEs. In this randomized, open-label, superiority, controlled, proof-of-concept clinical trial we are going to evaluate the early use of an anti-IL6 receptor inhibitor, tocilizumab,  compared to glucocorticoids, for treatment of ICI-induced arthritis.