TY - JOUR

T1 - Safety and efficacy of infliximab and corticosteroid therapy in checkpoint inhibitor-induced colitis

AU - Dahl, Emilie Kristine

AU - Abed, Osama Karim

AU - Kjeldsen, Jens

AU - Donia, Marco

AU - Svane, Inge Marie

AU - Dige, Anders

AU - Agnholt, Jørgen Steen

AU - Bjerrum, Jacob Tveiten

AU - Seidelin, Jakob Benedict

N1 - Publisher Copyright: © 2022 John Wiley & Sons Ltd.

PY - 2022

Y1 - 2022

N2 - Background: Cancer patients treated with immune check point inhibitors are at risk of developing severe colitis. However, the efficacy and safety of treatment of severe colitis is poorly understood. Aims: To explore the safety and efficacy of infliximab and corticosteroids in severe immune-mediated enterocolitis (IMC). Method: We performed a nationwide retrospective cohort study on 140 cancer patients treated with infliximab due to IMC in Denmark from 2011 to 2021. Results: The rate of complete remission with infliximab was 52% after one dose, increasing to 73% after two or more doses. Thirteen patients (10%) required additional treatment with vedolizumab. Patients were heavily exposed to corticosteroids and received a median accumulated dose of 3978 mg (interquartile range [IQR] 2552–6414). Age- and cancer-adjusted Cox regression analysis found that a high dose of prednisolone at start of tapering ≥75 mg/day was associated with increased mortality (HR 1.67, 1.04–2.69, p = 0.035). Patients responding to infliximab experienced an improvement of symptoms after 3 days (IQR 2–4) and complete remission after 31 days (IQR 14–61). Twenty-four percent required hospitalisation for infection during treatment for IMC, lasting 7 days (median). Secondary gastrointestinal infections occurred in 16%, with Clostridioides difficile being most common (64%). Further, 10% had a thromboembolic event during the first 90 days after infliximab treatment. Conclusions: Infliximab led to complete resolution of symptoms in 73% of patients with IMC. High prednisolone dose at tapering was associated with increased mortality rate and a high incidence of infections and hospitalisations in patients with severe IMC. We suggest optimised infliximab treatment before escalation of steroid doses.

AB - Background: Cancer patients treated with immune check point inhibitors are at risk of developing severe colitis. However, the efficacy and safety of treatment of severe colitis is poorly understood. Aims: To explore the safety and efficacy of infliximab and corticosteroids in severe immune-mediated enterocolitis (IMC). Method: We performed a nationwide retrospective cohort study on 140 cancer patients treated with infliximab due to IMC in Denmark from 2011 to 2021. Results: The rate of complete remission with infliximab was 52% after one dose, increasing to 73% after two or more doses. Thirteen patients (10%) required additional treatment with vedolizumab. Patients were heavily exposed to corticosteroids and received a median accumulated dose of 3978 mg (interquartile range [IQR] 2552–6414). Age- and cancer-adjusted Cox regression analysis found that a high dose of prednisolone at start of tapering ≥75 mg/day was associated with increased mortality (HR 1.67, 1.04–2.69, p = 0.035). Patients responding to infliximab experienced an improvement of symptoms after 3 days (IQR 2–4) and complete remission after 31 days (IQR 14–61). Twenty-four percent required hospitalisation for infection during treatment for IMC, lasting 7 days (median). Secondary gastrointestinal infections occurred in 16%, with Clostridioides difficile being most common (64%). Further, 10% had a thromboembolic event during the first 90 days after infliximab treatment. Conclusions: Infliximab led to complete resolution of symptoms in 73% of patients with IMC. High prednisolone dose at tapering was associated with increased mortality rate and a high incidence of infections and hospitalisations in patients with severe IMC. We suggest optimised infliximab treatment before escalation of steroid doses.

U2 - 10.1111/apt.17201

DO - 10.1111/apt.17201

M3 - Journal article

C2 - 36123319

AN - SCOPUS:85138244074

VL - 56

SP - 1370

EP - 1382

JO - Alimentary Pharmacology and Therapeutics, Supplement

JF - Alimentary Pharmacology and Therapeutics, Supplement

SN - 0953-0673

IS - 9

ER -