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Immune-related AEs due to checkpoint inhibitors require care coordination

EULAR 2020
Studies have shown that cancer treatment with checkpoint inhibitors can lead to rheumatic and musculoskeletal immune-related adverse events (irAEs), but clear guidance for rheumatologists to manage these events was lacking. An EULAR task force was set up to combine expert opinions on how to manage irAEs without jeopardising the response to the checkpoint inhibitor therapy [1].

The EULAR task force, consisting of 23 experts, developed 4 over-arching principles and 10 recommendations on the matter [1]. The 4 principles are:

  1. irAEs may occur during treatment with checkpoint inhibitors;
  2. shared decision-making between patients, oncologists, and rheumatologists is needed;
  3. rheumatologists should take an active role in engaging with oncologists when they are managing patients who have musculoskeletal signs and symptoms; and
  4. rheumatologists should assist in differential diagnosis and mitigate musculoskeletal symptoms to an acceptable level while enabling effective anti-tumour response in immune checkpoint inhibition.

The resulting 10 recommendations covered a wide spectrum of issues, such as awareness among rheumatologists of the different and varied presentations of irAEs (they can be atypical or have an incomplete presentation) as well as promoting consultation of the rheumatologist by the oncologist when a rheumatic event is first suspected. Symptomatic treatment including non-steroidal anti-inflammatory drugs or analgesics are the initial choice and, in case of inefficacy, local and/or systemic glucocorticoids should be considered. After glucocorticoids, conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) followed by biologic DMARDs can be used, with tumour necrosis factor (TNF) or interleukin(IL)-6 inhibitors being the recommended biologic agents.

Regarding the use of checkpoint inhibitors, the decision to cease or continue them needs to be based on the severity of irAEs, the extent of immunosuppression that is required to manage them, tumour response, and the future oncology treatment plan. A full rheumatologic assessment was recommended prior to immune checkpoint inhibition. Finally, it was noted that more research, for instance from well-organised trials, is urgently needed as evidence on how to manage irAEs is limited.  Also, it must be pointed out that higher doses of corticosteroid used to manage irAEs could potentially impact detrimentally on cancer survival, which is an important consideration for inflammatory arthritis therapy, which poses less of a threat to immediate survival than advanced cancer [2].

  1. Benesova K, et al. EULAR E-Congress, 3-6 June 2020.
  2. McGonagle D, et al. Autoimmunity Reviews 2020;19(2):102456.

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