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

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 corticoste-roids, 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.