Efficacy and safety of early use of IL-6R blockad versus glucocorticoids for the treatment of arthritis induced by check point inhibitors: a randomized, proof of concept, controlled clinical trial

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.