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

Publikation: Bidrag til tidsskriftTidsskriftartikelfagfællebedømt

Dokumenter

  • Fulltext

    Accepteret manuskript, 2,71 MB, PDF-dokument

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.

OriginalsprogEngelsk
TidsskriftAlimentary Pharmacology and Therapeutics
Vol/bind56
Udgave nummer9
Sider (fra-til)1370-1382
Antal sider13
ISSN0269-2813
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Emilie Kristine Dahl has served as a speaker for MSD and Tillotts Pharma. Osama Karim Abed, Jens Kjeldsen and Jacob Tveiten Bjerrum: none. Jørgen Agnholt: Advisory board: Ferring, Pharmaceuticals, AbbVie, Pfizer, Bristol‐Meyers Squibb. Speaker: Bristol‐Meyers Squibb, Takeda, Norgine, Janssen and Pfizer. Marco Donia: has received honoraria for lectures from Roche (past 2 years), is consultant of Achilles Therapeutics and received access to research data from Bristol Myers Squibb and from Genentech. Inge Marie Svane: has received research funding from Adaptimmune, Enara Bio, Evaxion, Lytix Biopharma, TILT Biotherapeutics, Bristol Myers Squibb, Novartis and Roche. Advisory Board honorary: Bristol Myers Squibb, Novartis and Pierre Fabre. Consultancy honoraria: Bristol Myers Squibb, MSD and IO Biotech. Speaker honorary: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre and Roche. Stock and Other Ownership Interests: IO Biotech. Jakob Benedict Seidelin: Research grants from Takeda and the Capital Region Denmark, national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly and Boehringer Ingelheim. Declaration of personal interests:

Funding Information:
Declaration of personal interests: Emilie Kristine Dahl has served as a speaker for MSD and Tillotts Pharma. Osama Karim Abed, Jens Kjeldsen and Jacob Tveiten Bjerrum: none. Jørgen Agnholt: Advisory board: Ferring, Pharmaceuticals, AbbVie, Pfizer, Bristol-Meyers Squibb. Speaker: Bristol-Meyers Squibb, Takeda, Norgine, Janssen and Pfizer. Marco Donia: has received honoraria for lectures from Roche (past 2 years), is consultant of Achilles Therapeutics and received access to research data from Bristol Myers Squibb and from Genentech. Inge Marie Svane: has received research funding from Adaptimmune, Enara Bio, Evaxion, Lytix Biopharma, TILT Biotherapeutics, Bristol Myers Squibb, Novartis and Roche. Advisory Board honorary: Bristol Myers Squibb, Novartis and Pierre Fabre. Consultancy honoraria: Bristol Myers Squibb, MSD and IO Biotech. Speaker honorary: Bristol Myers Squibb, MSD, Novartis, Pierre Fabre and Roche. Stock and Other Ownership Interests: IO Biotech. Jakob Benedict Seidelin: Research grants from Takeda and the Capital Region Denmark, national coordinator of studies from AbbVie, Arena Pharmaceuticals, Ely Lilly and Boehringer Ingelheim.

Publisher Copyright:
© 2022 John Wiley & Sons Ltd.

ID: 324823045