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Janus kinase 1 inhibitors for treating immune checkpoint inhibitor-induced enterocolitis - report of two filgotinib-treated cases and literature review

Ekedahl, Henrik LU ; Sigurjonsdottir, Gudbjörg LU ; Bergqvist, Viktoria LU ; Båtshake, Björn LU ; Carneiro, Ana LU orcid and Marsal, Jan LU orcid (2025) In Acta oncologica (Stockholm, Sweden) 64. p.1365-1370
Abstract

BACKGROUND AND PURPOSE: Treatment of cancer with immune checkpoint inhibitors (ICIs) entails a risk of immune-related adverse events (irAEs). Data on the treatment of immune-related enterocolitis (irEC) in patients with inadequate symptom control after treatment with standard therapy including corticosteroids, infliximab, and vedolizumab are scarce. Based on limited data, recommendations include treatment with the pan-Janus kinase (JAK) inhibitor tofacitinib. Filgotinib is a more recently developed JAK inhibitor with preferential inhibition of JAK1, which might imply a more favorable safety profile. Filgotinib is approved for the treatment of ulcerative colitis and might thus be an option in refractory irEC.

PATIENTS AND METHODS:... (More)

BACKGROUND AND PURPOSE: Treatment of cancer with immune checkpoint inhibitors (ICIs) entails a risk of immune-related adverse events (irAEs). Data on the treatment of immune-related enterocolitis (irEC) in patients with inadequate symptom control after treatment with standard therapy including corticosteroids, infliximab, and vedolizumab are scarce. Based on limited data, recommendations include treatment with the pan-Janus kinase (JAK) inhibitor tofacitinib. Filgotinib is a more recently developed JAK inhibitor with preferential inhibition of JAK1, which might imply a more favorable safety profile. Filgotinib is approved for the treatment of ulcerative colitis and might thus be an option in refractory irEC.

PATIENTS AND METHODS: We present two cases of metastatic melanoma treated with ICIs who developed corticosteroid and infliximab-refractory irEC. Given non-conventional pharmaceutical management, literature review was performed regarding mechanisms of action and safety profiles of JAK inhibitors.

RESULTS: Both patients were treated with filgotinib, which resulted in rapid remission of symptoms in both cases. One of the patients was treated with off-label high-dose filgotinib, which has not been described previously. The rationale and safety regarding the use of JAK1 inhibitors in irAEs are discussed, including the seemingly diverging existing data on potential effects of JAK inhibition on ICI-induced anti-tumoral immune-responses. In addition, the rationale for the high-dose treatment is scrutinized.

INTERPRETATION: This report suggests that filgotinib may be considered for treating irEC refractory to standard therapy.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Melanoma/drug therapy, Janus Kinase 1/antagonists & inhibitors, Immune Checkpoint Inhibitors/adverse effects, Male, Middle Aged, Enterocolitis/drug therapy, Female, Aged, Pyridines/therapeutic use, Protein Kinase Inhibitors/therapeutic use, Triazoles
in
Acta oncologica (Stockholm, Sweden)
volume
64
pages
1365 - 1370
publisher
Taylor & Francis
external identifiers
  • pmid:41055202
ISSN
1651-226X
DOI
10.2340/1651-226X.2025.44298
language
English
LU publication?
yes
id
8e0f4ffc-fd69-4d26-b2c4-ad4baed19847
date added to LUP
2025-10-07 22:02:17
date last changed
2025-10-08 07:29:30
@article{8e0f4ffc-fd69-4d26-b2c4-ad4baed19847,
  abstract     = {{<p>BACKGROUND AND PURPOSE: Treatment of cancer with immune checkpoint inhibitors (ICIs) entails a risk of immune-related adverse events (irAEs). Data on the treatment of immune-related enterocolitis (irEC) in patients with inadequate symptom control after treatment with standard therapy including corticosteroids, infliximab, and vedolizumab are scarce. Based on limited data, recommendations include treatment with the pan-Janus kinase (JAK) inhibitor tofacitinib. Filgotinib is a more recently developed JAK inhibitor with preferential inhibition of JAK1, which might imply a more favorable safety profile. Filgotinib is approved for the treatment of ulcerative colitis and might thus be an option in refractory irEC.</p><p>PATIENTS AND METHODS: We present two cases of metastatic melanoma treated with ICIs who developed corticosteroid and infliximab-refractory irEC. Given non-conventional pharmaceutical management, literature review was performed regarding mechanisms of action and safety profiles of JAK inhibitors.</p><p>RESULTS: Both patients were treated with filgotinib, which resulted in rapid remission of symptoms in both cases. One of the patients was treated with off-label high-dose filgotinib, which has not been described previously. The rationale and safety regarding the use of JAK1 inhibitors in irAEs are discussed, including the seemingly diverging existing data on potential effects of JAK inhibition on ICI-induced anti-tumoral immune-responses. In addition, the rationale for the high-dose treatment is scrutinized.</p><p>INTERPRETATION: This report suggests that filgotinib may be considered for treating irEC refractory to standard therapy.</p>}},
  author       = {{Ekedahl, Henrik and Sigurjonsdottir, Gudbjörg and Bergqvist, Viktoria and Båtshake, Björn and Carneiro, Ana and Marsal, Jan}},
  issn         = {{1651-226X}},
  keywords     = {{Humans; Melanoma/drug therapy; Janus Kinase 1/antagonists & inhibitors; Immune Checkpoint Inhibitors/adverse effects; Male; Middle Aged; Enterocolitis/drug therapy; Female; Aged; Pyridines/therapeutic use; Protein Kinase Inhibitors/therapeutic use; Triazoles}},
  language     = {{eng}},
  month        = {{10}},
  pages        = {{1365--1370}},
  publisher    = {{Taylor & Francis}},
  series       = {{Acta oncologica (Stockholm, Sweden)}},
  title        = {{Janus kinase 1 inhibitors for treating immune checkpoint inhibitor-induced enterocolitis - report of two filgotinib-treated cases and literature review}},
  url          = {{http://dx.doi.org/10.2340/1651-226X.2025.44298}},
  doi          = {{10.2340/1651-226X.2025.44298}},
  volume       = {{64}},
  year         = {{2025}},
}