Ignite Creation Date:
2024-05-06 @ 11:49 AM
Last Modification Date:
2024-10-26 @ 12:50 PM
Study NCT ID:
NCT03601611
Status:
COMPLETED
Last Update Posted:
2020-04-21
First Post:
2018-07-01
Brief Title:
Checkpoint Inhibitor Induced Colitis and Arthritis -Immunomodulation With IL-6 Blockade and Exploration of Disease Mechanisms
Sponsor:
Herlev Hospital
Organization:
Herlev Hospital
Study Overview
Official Title:
Checkpoint Inhibitor Induced Colitis and Arthritis -Immunomodulation With IL-6 Blockade and Exploration of Disease Mechanisms
Status:
COMPLETED
Status Verified Date:
2020-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
COLAR
Brief Summary:
Immune checkpoint inhibitors ICI might induce inflammatory potentially serious and even lethal immune related Adverse Events irAEs Diarrhea andor colitis are ones of the most frequently reported irAEs in patients taking ICI Although the immune mechanisms underlying irAEs have not been fully elucidated studies suggest that Th17 and Tregs cells increases in expression of immunologically-related genes eosinophilia microbiome among others and cytokines may be involved in the pathophysiology of immune-related complications in some diseases that resemble irAEs such as colitis and rheumatic manifestations Importantly interleukin-6 IL-6 promotes the differentiation of naïve CD4 T cells into Th17 cells 17 and IL-6 inhibition may rebalance the altered Th17-Treg axis without inhibiting the Th1-CD8 T-cell subsets that govern antitumor immunity These findings raise the possibility of using IL-6 blockade as a strategy for treating colitis and arthritis induced by immune checkpoint blockade
Detailed Description:
Immune checkpoint inhibitors ICI targeting cytotoxic T-lymphocyte-associated protein 4 CTLA-4 and the programmed cell death protein-1 PD-1programmed cell death ligand-1 PD-L1 pathway might induce inflammatory potentially serious and even lethal immune related Adverse Events irAEs Diarrhea andor colitis are ones of the most frequently reported irAEs in patients taking ICI occurring after an average of three infusions The incidence is higher among patients taking combination anti-CTLA-4 anti-PD-1 therapy 44 than those receiving anti-CTLA-4 23-33 or anti-PD-1 19 monotherapy The most common autoimmune and musculoskeletal irAEs reported in clinical trials are represented by arthralgia and arthritis The incidence of arthralgia andor inflammatory arthritis secondary to nivolumab therapy ranges from 5 to 16 and 5 respectively Although the immune mechanisms underlying irAEs have not been fully elucidated studies suggest that Th17 and Tregs cells increases in expression of immunologically-related genes eosinophilia microbiome among others and cytokines may be involved in the pathophysiology of immune-related complications in some diseases that resemble irAEs such as colitis and rheumatic manifestations Previous studies report Th-17 that drives interleukin-17 IL-17 production as a key mediator of many immune diseases including inflammatory bowel disease and ICI-induced colitis and IL-17 elevations have been observed in experimental colitis Importantly interleukin-6 IL-6 promotes the differentiation of naïve CD4 T cells into Th17 cells 17 and IL-6 inhibition may rebalance the altered Th17-Treg axis without inhibiting the Th1-CD8 T-cell subsets that govern antitumor immunity An imbalance of Th17Treg may cause the onset and progression of immune-mediated side effects Thus a 3-fold increase of IL-17 and IL-6 by week 12 concomitant with the development of fulminant colitis has been reported in a patient who developed presumed ipilimumab-induced colitis These findings raise the possibility of using IL-6 blockade as a strategy for treating colitis and arthritis induced by immune checkpoint blockade
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None