Use of Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Autoimmune Disease: A Systematic Review

Ann Intern Med. 2018 Jan 16;168(2):121-130. doi: 10.7326/M17-2073. Epub 2018 Jan 2.


Background: Cancer immunotherapy with checkpoint inhibitors (CPIs) is associated with frequent immune-related adverse events (irAEs) and is often not recommended for patients with concomitant autoimmune disease.

Purpose: To summarize the evidence on adverse events associated with CPIs in patients with cancer and preexisting autoimmune disease.

Data sources: MEDLINE, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials through September 2017 with no language restrictions.

Study selection: Original case reports, case series, and observational studies describing patients with cancer and autoimmune disease who were receiving CPIs.

Data extraction: 2 reviewers independently extracted data and assessed the quality of reporting.

Data synthesis: 123 patients in 49 publications were identified; 92 (75%) had exacerbation of preexisting autoimmune disease, irAEs, or both. No differences in adverse events were observed in patients with active versus inactive disease. Patients receiving immunosuppressive therapy at initiation of CPI therapy seemed to have fewer adverse events than those not receiving treatment. Most flares and irAEs were managed with corticosteroids; 16% required other immunosuppressive therapies. Adverse events improved in more than half of patients without discontinuation of CPI therapy. Three patients died of adverse events.

Limitations: The quality and quantity of data were limited. Case reports typically describe unique manifestations and are not generalizable to the population at large. Because there were no prospective observational studies, incidence could not be determined.

Conclusion: Flares and irAEs in patients with autoimmune disease who are receiving CPIs can often be managed without discontinuing therapy, although some events may be severe and fatal. Prospective longitudinal studies are needed to establish incidence of adverse events and evaluate risk-benefit ratios and patient preferences in this population.

Primary funding source: National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Systematic Review

MeSH terms

  • Antineoplastic Agents, Immunological / adverse effects*
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Cell Cycle Checkpoints / drug effects*
  • Humans
  • Immunotherapy / methods*
  • Neoplasms / complications
  • Neoplasms / drug therapy*
  • Neoplasms / immunology


  • Antineoplastic Agents, Immunological