Balancing immunosuppression and cancer survival in the treatment of immune checkpoint inhibitor–associated inflammatory arthritis

Immune checkpoint inhibitors (ICI) block regulators of T cell activation, break tolerance and restore antitumour immunity but are commonly associated with off-target autoimmune side effects, including ICI inflammatory arthritis (ICI-IA), which occurs in 6% of treated individuals. ICI-IA often resembles rheumatoid arthritis (RA); however, unlike in RA, the ICI-IA synovium is characterised by an expansion of CD38 + CD127 - PD1 + CD8 + T cells, interleukin (IL)-1β hi macrophages and a strong interferon signature. Tumour necrosis factor (TNF) and IL-6 levels are also upregulated in the ICI-IA joint. Treatment of ICI-IA must consider the potentially deleterious effects of immunosuppression on cancer outcomes in the ICI context. Modest doses of glucocorticoids appear to be safe. Methotrexate can also be used and may be associated with better cancer progression-free survival than TNF inhibition. For severe ICI-IA cases requiring rapid arthritis control, IL-6 receptor inhibitors can be used, and they are more likely to allow resumption/continuation of ICI than treatment with glucocorticoids alone.