Rheumatic immune related adverse events in patients treated with checkpoint inhibitors for immunotherapy of cancer

Immune checkpoints are small molecules expressed by immune cells that play critical roles in maintaining immune homeostasis. Immune checkpoint inhibitors (ICPIs) are new cancer drugs that target self-tolerance pathways exploited by tumors to escape immune destruction, such as cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) or its ligand (PD-L1). Several ICPIs have been approved by Food and Drug Administration, increasing overall survival with different cancers. However, their use can determine development of many different inflammatory side effects, that are defined immune-related adverse effects (irAEs); among others, rheumatological irAEs can develop in these patients. Currently, we have limited data about these adverse effects; particularly, few evidence come from clinical trials about patients with pre-existing autoimmune diseases because they were excluded from them. Therefore we analysed the existing scientific literature dealing with this issue, in order to answer to different clinical questions. According to all reviewed data, rheumatological irAEs are not infrequent, in both previously diseased and undiseased patients, but they are often mild and reversible. Close monitoring and interdisciplinary management and monitoring is necessary in order to ensure best care. Many questions remain unanswered or not completely answered; further data are necessary to implement our knowledge in this field and to standardize and optimize clinical practice.