Upadacitinib Results in Endoscopic Remission in Patients With Inflammatory Bowel Disease and Prior Tofacitinib...

Assess the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure.

Patients with severe, refractory Crohn's disease (CD) or ulcerative colitis (UC) and inadequate response to medical therapy have a high risk of complications. A better understanding of treatment response in the setting of prior failure may improve disease control in high-risk patients. Currently, the response to a subsequent Janus Kinase (JAK) inhibitor after prior JAK failure is poorly understood.

We retrospectively assessed the safety and effectiveness of upadacitinib in patients with prior tofacitinib failure.

We report on 26 patients (10 UC, 16 CD) treated with upadacitinib after tofacitinib failure. Mean age 40.2 years, mean disease duration 14.4 years (range 2 to 33), and previously failed a median of 5 advanced therapies. The mean upadacitinib treatment duration was 13.9 months (SD 4.5). On upadacitinib, 83.3% (n=10/12) of patients achieved clinical response, 66.7% (n=8/12) clinical remission, 71.4% (n=10/14) endoscopic improvement, 57.1% (n=8/14) endoscopic remission, and 35.7% (n=5/14) endoscopic healing. The mean Simple Endoscopic Score in CD decreased from 14.3 (SD: 8.3) to 8.6 (SD: 9.0) ( P =0.24). The mean Mayo Endoscopic Subscore significantly decreased from 2.7 (SD 0.8) to 0.9 (SD 1.2) ( P =0.006). 73.1% of patients on upadacitinib reported adverse events, most commonly minor infections and acne. No serious adverse events, major cardiovascular events, malignancies, or Shingles were observed.

Upadacitinib was tolerated in most patients and resulted in clinical and endoscopic improvement in the majority of patients with severe, refractory CD or UC with prior tofacitinib failure, regardless of previous clinical response to tofacitinib. Further studies would define the long-term safety, efficacy, and predictors of response after previous JAK exposure.