EULAR points to consider for the diagnosis and management of rheumatic immune-related adverse events due to cancer immunotherapy with checkpoint inhibitors

Ann Rheum Dis. 2021 Jan;80(1):36-48. doi: 10.1136/annrheumdis-2020-217139. Epub 2020 Apr 23.


Background: Rheumatic and musculoskeletal immune-related adverse events (irAEs) are observed in about 10% of patients with cancer receiving checkpoint inhibitors (CPIs). Given the recent emergence of these events and the lack of guidance for rheumatologists addressing them, a European League Against Rheumatism task force was convened to harmonise expert opinion regarding their identification and management.

Methods: First, the group formulated research questions for a systematic literature review. Then, based on literature and using a consensus procedure, 4 overarching principles and 10 points to consider were developed.

Results: The overarching principles defined the role of rheumatologists in the management of irAEs, highlighting the shared decision-making process between patients, oncologists and rheumatologists. The points to consider inform rheumatologists on the wide spectrum of musculoskeletal irAEs, not fulfilling usual classification criteria of rheumatic diseases, and their differential diagnoses. Early referral and facilitated access to rheumatologist are recommended, to document the target organ inflammation. Regarding therapeutic, three treatment escalations were defined: (1) local/systemic glucocorticoids if symptoms are not controlled by symptomatic treatment, then tapered to the lowest efficient dose, (2) conventional synthetic disease-modifying antirheumatic drugs, in case of inadequate response to glucocorticoids or for steroid sparing and (3) biological disease-modifying antirheumatic drugs, for severe or refractory irAEs. A warning has been made on severe myositis, a life-threatening situation, requiring high dose of glucocorticoids and close monitoring. For patients with pre-existing rheumatic disease, baseline immunosuppressive regimen should be kept at the lowest efficient dose before starting immunotherapies.

Conclusion: These statements provide guidance on diagnosis and management of rheumatic irAEs and aim to support future international collaborations.

Keywords: arthritis; autoimmunity; inflammation; multidisciplinary team care; treatment.

Publication types

  • Consensus Development Conference
  • Practice Guideline
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Advisory Committees
  • Analgesics / therapeutic use
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antirheumatic Agents / therapeutic use*
  • Arthralgia / chemically induced
  • Arthralgia / diagnosis
  • Arthralgia / immunology
  • Arthralgia / therapy
  • Arthritis, Psoriatic / chemically induced
  • Arthritis, Psoriatic / diagnosis
  • Arthritis, Psoriatic / immunology
  • Arthritis, Psoriatic / therapy
  • Arthritis, Reactive / chemically induced
  • Arthritis, Reactive / diagnosis
  • Arthritis, Reactive / immunology
  • Arthritis, Reactive / therapy
  • Autoantibodies / immunology
  • Decision Making, Shared
  • Deprescriptions
  • Europe
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects*
  • Immunoglobulins, Intravenous / therapeutic use
  • Immunologic Factors / therapeutic use
  • Medical Oncology
  • Methotrexate / therapeutic use
  • Myalgia / chemically induced
  • Myalgia / diagnosis
  • Myalgia / immunology
  • Myalgia / therapy
  • Myocarditis / chemically induced
  • Myocarditis / diagnosis
  • Myocarditis / immunology
  • Myocarditis / therapy
  • Myositis / chemically induced
  • Myositis / diagnosis
  • Myositis / immunology
  • Myositis / therapy
  • Neoplasms / drug therapy*
  • Plasma Exchange
  • Polymyalgia Rheumatica / chemically induced
  • Polymyalgia Rheumatica / diagnosis
  • Polymyalgia Rheumatica / immunology
  • Polymyalgia Rheumatica / therapy
  • Rheumatic Diseases / chemically induced
  • Rheumatic Diseases / diagnosis
  • Rheumatic Diseases / immunology
  • Rheumatic Diseases / therapy*
  • Rheumatology
  • Severity of Illness Index
  • Societies, Medical
  • Tumor Necrosis Factor Inhibitors / therapeutic use


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antirheumatic Agents
  • Autoantibodies
  • Glucocorticoids
  • Immune Checkpoint Inhibitors
  • Immunoglobulins, Intravenous
  • Immunologic Factors
  • Tumor Necrosis Factor Inhibitors
  • Methotrexate