Background/Purpose: A systematic review of case reports to summarize the existing evidence on the use of checkpoint inhibitors in patients with cancer and preexisting autoimmune diseases.

Methods: We searched Medline, EMBASE, Web of Science, PubMed ePubs, and the Cochrane Central Register of Controlled Trials (CENTRAL) through January 2016 with no restrictions. References cited in the included articles were searched manually. We included case reports describing patients with cancer and autoimmune disease diagnosed before starting treatment with the checkpoint inhibitors. We extracted data on patient’s characteristics, type of checkpoint inhibitors, reported immune related adverse events (irAEs), how they were managed, and their clinical outcome, if discontinuation of immunotherapy was required, and if treatment rechallenge was reported.

Results: Fourteen publications met inclusion criteria, reporting on 45 cases. Age of the cases ranged from 30 to 80 years; 25 patients (55.6%) were male. Forty three cases (95.6%) had melanoma. Preexisting autoimmune diseases included autoimmune thyroid diseases, rheumatoid arthritis, ulcerative colitis, psoriasis (two with psoriatic arthritis), multiple sclerosis, Crohn’s disease, sarcoidosis, systemic lupus, Behcet disease, inflammatory arthritis, reactive arthritis, rheumatic fever, Sjogren’s syndrome, transverse myelitis, and celiac disease. Of the 45 cases, 86.8% received concomitant treatment (corticosteroids, DMARDs, and biologics) for their autoimmune disease; 53.9% were still active at the time of immune checkpoint inhibitor therapy. Most received ipilimumab (88.9%). After immunotherapy: 1) 40.0% reported de novo irAEs, 2) 28.9% reported exacerbation of the preexisting autoimmune disease, 3) 8.9% reported both, and 4) 40.0% did not report any adverse events. Hypophysitis and colitis occurred in most cases (27.8% each) with de novo irAEs. Autoimmune thyroiditis, diabetes, glaucoma, interstitial nephritis, skin itching, and toxic epidermal necrolysis were also reported. Those with exacerbation of the preexisting autoimmune disease, had manifestations similar to those occurring before checkpoint therapy, and none developed new disease features. Patients were treated with corticosteroids and hormonal replacement therapy. Therapy with azathioprine, sulfasalazine, or infliximab was also reported. Discontinuation of immunotherapy was recommended in 33.3%, and resolution of irAEs was achieved in the majority of cases. Death was reported in one case with toxic epidermal necrolysis and in another with severe colitis. Treatment rechallenge was reported in a patient with ulcerative colitis who developed exacerbation of his colitis after initial use of ipilimumab. Upon rechallenge, he reported grade III anterior panhypopitutarism and tracheobronchitis. In a patient with pulmonary sarcoidosis, ipilimumab rechallenge was not associated with significant clinical symptoms.

Conclusion: Forty percent of the cases did not experience irAE or disease exacerbation, despite many having active autoimmune disease at the time of checkpoint inhibition. Further studies are needed to establish the risk-benefit profile of this novel therapy in this population.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/use-of-immune-checkpoint-inhibitors-in-the-treatment-of-patients-with-cancer-and-preexisting-autoimmune-diseases-a-systematic-review-of-case-reports/