A Case of Immunotherapy-Induced Colitis Complicated by Perforation and Treated with Infliximab Postoperatively

Delasos, Lukas; Desai, Aakash; Lia, Nerea Lopetegui; Kethireddy, Nikhila; Ray, Carolyn

doi:10.1155/2019/9069354

Cited by 7 publications

(6 citation statements)

References 27 publications

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“…Other cases of intestinal perforation cases have been reported, but these cases were induced by anti-CTLA-4 antibodies. There were 2 other cases where combination of anti-CTLA-4 and anti-PD-L1 antibodies were used [ 12 , 13 ]. To our knowledge, this is the third case of anti-PD-1 monotherapy induced intestinal perforation.…”

Section: Discussionmentioning

confidence: 99%

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

Cho

Kim

et al. 2021

Ann Coloproctol

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With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

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Section: Discussionmentioning

confidence: 99%

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

Cho

Kim

et al. 2021

Ann Coloproctol

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“…While the anti-TNF-α antibody preparation IFX, a standard therapeutic agent for common ulcerative colitis, has been suggested as an effective treatment for irAEs, no specific IFX doses and dosing intervals have been recommended for this. Moreover, many reports have used IFX for enteritis in accordance with the treatment of ulcerative colitis (3)(4)(5)(6)(7)(8)(9)(10)(11). Pagès et al (6) proposed early administration of IFX 5-10 mg/kg/day when systemic steroid treatment failed to produce any appreciable symptomatic improvement 2/3 days after the onset of IPI-induced irAEs.…”

Section: Discussionmentioning

confidence: 99%

“…In line with this, steroid therapy with approximately 1 mg/kg/day prednisolone (PSL) equivalent is immediately initiated for grade 3 diarrhea/colitis. However, when symptoms do not improve, infliximab (IFX) treatment, generally at a dose of 5 mg/kg/day according to the Efficacy and safety of Infliximab for steroid-resistant immune-related adverse events: A retrospective study administration for ulcerative colitis (3)(4)(5)(6)(7)(8)(9)(10)(11), has been recommended. Single-dose IFX administration has often been selected as an irAE treatment, with additional doses administered only when no improvements occur after the first dose.…”

Section: Introductionmentioning

confidence: 99%

“…However, it is imperative to pre-emptively identify symptoms of medium-and long-term adverse reactions such as infectious diseases, demyelinating diseases, aplastic anemia, malignant tumors, autoimmune diseases, and heart failure, among which infectious diseases are of particular concern. Several case reports have described successful treatment of steroid-resistant ICI-induced diarrhea/colitis with IFX in patients receiving ipilimumab (IPI), an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody preparation (3)(4)(5)(6), as well as anti-programmed cell death-1 (PD-1) antibody or anti-programmed cell death-ligand 1 (PD-L1) antibody preparations (7)(8)(9)(10)(11). However, we were unable to identify any report systematically dealing with the required number of IFX doses or the time to switch to after treatment.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of Infliximab for steroid‑resistant immune‑related adverse events: A retrospective study

et al. 2021

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The present study investigated outcomes of infliximab (IFX) treatment among 8 Japanese patients with various types of cancer (4 with malignant melanoma, 3 with lung cancer and 1 with renal cancer) who developed severe steroid-resistant immune-related adverse events (irAEs) in association with immune checkpoint inhibitors (ICIs) to determine its efficacy and safety. Information, including patient background, treatment progress, examination data and imaging data, was collected retrospectively from electronic medical records. Adverse reactions were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Specific ICIs used were anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibody preparations in 7, 2 and 5 patients, respectively. Specific irAEs included grade 3 diarrhea/colitis in 7 patients and disseminated intravascular coagulation and myocarditis attributed to autoimmune activation in 1 patient. The median duration between systemic steroid and IFX treatments was 9 (range, 2-39) days. A total of 3 patients responded to IFX, 1 of whom responded after one dose and 2 responded after two doses. Respective diseases improved to grade 0 after a median of 18 (range, 9-32) days. No AEs were attributable to IFX. Additionally, anti-cytomegalovirus (CMV) and antibacterial agents were administered in parallel given the presence of CMV and Clostridium difficile (CD) infections in all patients, except in 1 exhibiting a marked IFX response after one dose. The combination of highly immunosuppressive IFX and high-dose systemic steroid administration over a long period presumably predisposed the patients to opportunistic enteric infections. Accordingly, early initiation of IFX treatment in conjunction with systemic steroid therapy should be considered for severe diarrhea/colitis and other irAEs. However, the possibility for CMV and CD infections should be recognized, and for these the treatment strategy may need to be modified at an early stage.

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“…Due to this, we evaluated some surface molecules involved in the mechanism of immune regulation in both DT-MSCs and CD3 + T-cells. In this sense, the expression of the adhesion molecules intracellular adhesion molecule (ICAM)-I and vascular cell adhesion molecule (VCAM)-I in MSCs favors the decrease in proliferation in splenocytes activated with anti-CD3 antibodies [45]; additionally, both adhesion molecules can induce the expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which is related to the suppressive action and to the inhibition of T-cell proliferation [46,47]. We found that after four days of culture, the expression of CTLA-4 in T-cells of co-cultures with MSCs from all four sources significantly increased, coinciding with the decrease in T-cell proliferation; this suggests the participation of CTLA-4 + Tregs for this inhibition to occur.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells

Rosa-Ruiz

Álvarez-Pérez

Cortés-Morales

et al. 2019

Cells

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Bone marrow mesenchymal stem/stromal cells (BM-MSCs) have immunoregulatory properties and have been used as immune regulators for the treatment of graft-versus-host disease (GVHD). Human dental tissue mesenchymal stem cells (DT-MSCs) constitute an attractive alternative to BM-MSCs for potential clinical applications because of their accessibility and easy preparation. The aim of this in vitro study was to compare MSCs from dental pulp (DP-MSCs), gingival tissue (G-MSCs), and periodontal ligament (PDL-MSCs) in terms of their immunosuppressive properties against lymphoid cell populations enriched for CD3+ T cells to determine which MSCs would be the most appropriate for in vivo immunoregulatory applications. BM-MSCs were included as the gold standard. Our results demonstrated, in vitro, that MSCs from DP, G, and PDL showed immunoregulatory properties similar to those from BM, in terms of the cellular proliferation inhibition of both CD4+- and CD8+-activated T-cells. This reduced proliferation in cell co-cultures correlated with the production of interferon-γ and tumor necrosis factor alpha (TNF-α) and the upregulation of programmed death ligand 1 (PD-L1) in MSCs and cytotoxic T-cell-associated Ag-4 (CTLA-4) in T-cells and increased interleukin-10 and prostaglandin E2 production. Interestingly, we observed differences in the production of cytokines and surface and secreted molecules that may participate in T-cell immunosuppression in co-cultures in the presence of DT-MSCs compared with BM-MSCs. Importantly, MSCs from four sources favored the generation of T-cell subsets displaying the regulatory phenotypes CD4+CD25+Foxp3+ and CD4+CD25+CTLA-4+. Our results in vitro indicate that, in addition to BM-MSCs, MSCs from all of the dental sources analyzed in this study might be candidates for future therapeutic applications.

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A Case of Immunotherapy-Induced Colitis Complicated by Perforation and Treated with Infliximab Postoperatively

Cited by 7 publications

References 27 publications

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report

Efficacy and safety of Infliximab for steroid‑resistant immune‑related adverse events: A retrospective study

Mesenchymal Stem/Stromal Cells Derived from Dental Tissues: A Comparative In Vitro Evaluation of Their Immunoregulatory Properties Against T cells

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