From May 2013 to May 2019, 118/1507 (7.8%) patients developed significant
colitis; 80/553 (14.5%) after PD1+CTLA-4, 35/1000 (3.5%) PD1 alone, and three patients after
Ipilimumab (IPI) alone. Combination
therapy-induced
colitis was more frequent (14.5% vs 3.5% in PD1 alone, p=<0.0001), had an earlier onset (6.3 weeks vs 25.7 weeks, p=<0.001), was more severe (grade 3/4 69% vs 31%, p=<0.001), and are more likely to require higher doses of
steroids (91% vs 74%, p=0.01) than PD1
colitis. Among all patients treated with
steroids (N=114), 54 (47%) responded and required no further
therapy (
steroid sensitive), 47 patients (41%) responded to
infliximab (
infliximab sensitive), and 13 (11%) were
infliximab refractory and needed further immunosuppressive drugs.
Infliximab-refractory patients all had onset within 4 weeks of
immunotherapy commencement and were more likely to have an underlying
autoimmune disease, have higher grade
colitis, and require longer immunosuppression, yet had similar response and survival than other patients with
colitis. Of 43 (37%) patients re-resumed treatment with PD1 monotherapy after
colitis resolution, 16 (37%) of whom developed recurrent
colitis. Endoscopic and histopathologic data were available for 64 patients. Most had left-sided
colitis, with an increase in chronic inflammatory cells and neutrophils within the lamina propria, an increase in neutrophils in the surface epithelium, without increased lymphocytes or increased eosinophils.
Infliximab-refractory
colitis had a trend towards more confluent pancolitis with
edema,
erythema, ulceration, and absent vascularity with neutrophilic infiltration and erosion.
CONCLUSION: