Table 1:

Summary of studies describing IBD exacerbations following CPI therapy.

	Cancer type	CPI therapy	#of patients with AID	Post CPI autoimmune complications	Status of AID at CPI start	Severity of flares/irAEs	#of patients with preexisting IBD	Frequency of IBD flares	Additional irAEs in IBD patients
Johnson et al [7]	Advanced melanoma	Ipilimumab	30	27% had exacerbation of AID. 33% had conventional grade 3–5 irAE	43% were on immunosuppressive therapy. Minimal to no symptoms prior to CPI start	Most autoimmune complications managed with corticosteroids	6 total: 2 UC patients and one Crohn’s patient had prior colectomies. All were asymptomatic or minimally symptomatic prior to CPI start	2/6 (33%) developed CPI induced colitis or IBD flare. 1 patient with UC with prior colectomy developed AID exacerbation. 1 patient with Crohn’s developed CPI induced colitis
Menzies et al. [5]	Advanced melanoma	Anti-PD-1	52	38% had AID flares	29% had active symptoms. 62% were not on immunosuppression at baseline	Generally mild and only 2 (4%) discontinued therapy due to flare. Flares more frequent in those with active symptoms or on immune-suppressants	6 with underlying GI disease: UC with colectomy: 2, Crohn’s: 3, Celiac: 1	None
Gutzmer et al. [22]	Advanced melanoma	Anti-PD-1	19	42% had AID flare	6/19 (32%) were on immunosuppressive therapy Preexisting autoimmunity controlled in all patients	All flares were managed by immunosuppressive and/or symptomatic therapy and did not require CPI termination	1 patient with UC on sulfasalazine and budesonide	1/1 patient had IBD flare – managed with steroids and interruption of anti-PD-1 and subsequently retreated without further exacerbation
Abdel-Wahab et al. [4] (a)	Metastatic melanoma, lung cancer, RCC, Merkel cell cancer	Ipilimumab, anti-PD-1, anti-PD-L1, or combination ipilimumab + anti-PD-1	123	50% had exacerbation of AID. 75% had exacerbation of AID, irAE, or both	46.2% had active AID. 43.6% were on treatment for AID. No differences observed in flares between those with active vs inactive AID at baseline	Most flares and irAEs managed with steroids. 16% required other immunosuppressives. More than half of patients improved without CPI discontinuation	13 total: UC: 8 Crohn’s: 55 had active disease. 4 were receiving treatment	5/13 (39%) had IBD flare. 3/5 with active disease did not have flare. One patient with UC experienced life- threatening perforation	Overall 62% had adverse event (exacerbation, new irAE or both). irAEs: De novo colitis, toxic epidermal necrolysis
Leonardi et al. [6]	NSCLC	Anti-PD-1 or anti-PD-L1	56	55% had AID flare and/or an irAE 13 (23%) had flare of preexisting AID	18% had active AID symptoms 20% were on immunomodulatory agents Minority had symptoms, all low-grade severity 50% who were symptomatic vs 18% who were asymptomatic developed AID flare post CPI	Exacerbations were generally mild 4/13 patients who developed exacerbation of AID required systemic corticosteroids	6 total: UC: 3 Crohn’s: 3 One patient was symptomatic at the start of therapy	None	3/6 developed other irAEs: 2 pneumonitis, one leukopenia
Kahler et al. [21]	Metastatic melanoma	Ipilimumab	41	12/41 (29.2%) experienced AID flare	11 (26.8%) were on immunosuppressants	Most were manageable	3 total: UC: 2 Crohn’s: 1	1/3 (33%) had IBD flare	Pruritis grade 3 and maculopapular exanthema grade 2 in Crohn’s patient

^a: This study is a systematic review of the literature that includes cases from Johnson et al. and Gutzmer et al. Abbreviations: AID: Autoimmune Disease; CPI: Checkpoint Inhibitor; GI: Gastrointestinal; IBD: Inflammatory Bowel Disease; irAE: Immune Related Adverse Event; NSCLC: Non-Small Cell Lung Cancer; RCC:Renal Cell Carcinoma; UC: Ulcerative Colitis