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Clinical case
Rheumatic immune-related adverse events of checkpoint therapy for cancer: case series of a new nosological entity
  1. C Calabrese1,2,
  2. E Kirchner1,2,
  3. A Kontzias1,2,
  4. V Velcheti1,3 and
  5. L H Calabrese1,2
  1. 1Cleveland Clinic Foundation, Cleveland, Ohio, USA
  2. 2Department of Rheumatology and Immunology, Cleveland Clinic, Cleveland, Ohio, USA
  3. 3Department of Hematology and Oncology, Cleveland Clinic, Cleveland, Ohio, USA
  1. Correspondence to Dr Leonard H Calabrese; calabrl{at}


Immunotherapy of cancer with checkpoint inhibitors has been associated with a spectrum of autoimmune and systemic inflammatory reactions known as immune-related adverse events (irAEs). Rheumatic irAEs are infrequently reported and extensively described. Here, we report our experience over an 18-month period with 15 patients evaluated in the rheumatology department for rheumatic irAEs. We identified 13 patients without pre-existing autoimmune disease (AID) who subsequently developed rheumatic irAEs, and two with established AID referred pre-emptively. irAEs encountered included: inflammatory arthritis, sicca syndrome, polymyalgia rheumatica-like symptoms and myositis. All cases required glucocorticoids, and three required a biological agent. Rheumatic irAEs led to temporary or permanent cessation of immunotherapy in all but five patients. One patient with pre-existing AID experienced a flare after starting immunotherapy. Our findings underscore that rheumatic irAEs are complex, at times require additional immunosuppressive therapy, and may influence ongoing immunotherapy regimens for the primary disease. Similar irAEs will be increasingly seen as checkpoint inhibitors adopted as standard of care in the community.

  • Autoimmune Diseases
  • Inflammation
  • Multidisciplinary team-care

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  • Correction notice This article has been corrected since it first published. The third author of this paper should be cited as ‘Kontzias A’.

  • Twitter Follow cassandra calabrese @CCalabreseDO

  • Contributors All authors contributed to data acquisition, analysis and manuscript preparation.

  • Competing interests LHC reports personal fees from Bristol-Myers Squibb, outside the submitted work. VV reports grants and personal fees from Bristol-Myers Squibb, grants and personal fees from Genentech, grants and personal fees from Merck, grants and personal fees from Astra Zeneca, personal fees from Celgene, grants and personal fees from Genoptix, personal fees from Foundation medicine, outside the submitted work. CC, KK and EK have nothing to disclose.

  • Ethics approval Cleveland Clinic Foundation IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional data are available.