Safety and efficacy of infliximab and corticosteroid therapy in checkpoint inhibitor-induced colitis
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Safety and efficacy of infliximab and corticosteroid therapy in checkpoint inhibitor-induced colitis. / Dahl, Emilie Kristine; Abed, Osama Karim; Kjeldsen, Jens; Donia, Marco; Svane, Inge Marie; Dige, Anders; Agnholt, Jørgen Steen; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict.
I: Alimentary Pharmacology and Therapeutics, Bind 56, Nr. 9, 2022, s. 1370-1382.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 324823045