Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

Abstract

PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

Immune Manifestations with Checkpoint Inhibitors in a Single Brazilian Center: Experience and Literature Review

“…The same appears to occur with stool frequency and colitis with ICIs, and they can occur more in combination therapy. In our series, around 10% of the patients (18 patients from 123) had GI complaints, a somewhat smaller number from those reported in other studies that were as high as 30% in some series with established autoimmune inflammatory bowel disease that required biologic therapy [18]. However, in most of the series, it is unclear whether inflammatory autoimmune disease was present.…”

Autoimmune complications of immunotherapy: pathophysiology and management

“…A prospective observational study of 751 cancer patients (85 with an autoimmune disease) treated with anti-PD1 showed that irAEs were more common in patients with an underlying autoimmune disease than in those without, 66%, (50 to 86) versus 40% (35 to 45) but that high grade irAEs occurred with similar frequencies, 9.4% (4.1 to 19) versus 8.8% (6.7 to 11.4)50 (in that study, no relationship was seen between the presence of an autoimmune disease and progression free or overall survival). In a retrospective cohort study of 102 patients with pre-existing inflammatory bowel disease treated with ICIs, 41% experienced gastrointestinal adverse events compared with 11% in patients without inflammatory bowel disease (odds ratio, 3.61; 95% confidence interval 0.85 to 15.27; P=0.081), but the incidence of de novo irAEs was not reported 51. A systematic review of case reports, case series, and observational studies detailed clinical features in 123 patients with autoimmune disease who were treated with ICIs.…”

Pathologic Manifestations of Gastrointestinal and Hepatobiliary Injury in Immune Checkpoint Inhibitor Therapy

“…36 Owing to the immune dysregulation effects of CPI therapy, patients with autoimmune diseases and IBD were largely excluded from the CPI clinical trials. A recent study 46 revealed that both anti-CTLA-4 and anti-PD-1/PD-L1 therapies for patients with preexisting IBD were overall safe, but patients with preexisting IBD had a higher risk of severe colonic adverse events, such as high grades of diarrhea and colitis, high rates of colonic perforation, and frequent recurrence, than did patients without preexisting IBD. The distinction between IBD flare/recurrence and CPI-induced chronic active colitis is difficult, and clinical correlation is required for optimal management.…”