Background Behçet’s syndrome encompasses a cluster of chronic systemic vascular inflammatory conditions affecting multiple organs, with intestinal involvement termed intestinal Behçet’s disease. The current understanding of treatment for intestinal Behçet’s disease is limited. Anti-tumor necrosis factor (TNF) is recommended for moderately severe, severe, and refractory intestinal Behçet’s disease. Yet, managing patients resistant to this therapy remains daunting. No study has reported on the treatment of intestinal Behçet’s disease with Upadacitinib, a Janus kinase inhibitor. Herein, we present the four cases with ineffective anti-TNF therapy who were treated with upadacitinib.

Methods We retrospectively collected the clinical data of patients with intestinal Behçet’s disease treated with upadacitinib at the First Affiliated Hospital of Zhejiang University School of Medicine, including clinical manifestations, medication usage, imaging examinations, and indicators such as blood count, liver and kidney function, erythrocyte sedimentation rate, C-reactive protein, and endoscopic findings before and after treatment.

Results Four patients all had a history of recurrent oral ulcers and abdominal symptoms, with endoscopic evidence of an ileocecal ulcer. After prior therapy of anti-TNF, three patients exhibited either stagnation or exacerbation of ulcerative pathology and clinical manifestations, prompting a therapeutic transition to upadacitinib. One patient experienced an improvement in the primary ulcer but encountered the emergence of a vulvar ulcer, resulting in the addition of upadacitinib alongside adalimumab. After a follow-up period ranging from 5 to 9 months, all patients demonstrated notable symptomatic amelioration, with either a reduction or stabilization in the prescribed glucocorticoids or immunosuppressants. Three patients exhibited complete healing of the endoscopic ulcer, while one patient, with a 5-month follow-up, had a significantly smaller ulcer. All four patients presented decreased erythrocyte sedimentation rate and C-reactive protein levels, as well as increased hemoglobin and albumin levels. No serious adverse events were reported in either of the four patients during follow-up.

Conclusions Upadacitinib can be considered for Anti-TNF-Refractory intestinal Behçet’s disease.