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Response to Upadacitinib in Patients with Inflammatory Bowel Disease Previously Treated with Tofacitinib
Tarek Odah1, Christian Karime2, Aakash Desai3
1Division of Gastroenterology and Hepatology, Inflammatory Bowel Disease Center, Mayo Clinic, 4500 San Pablo Rd S., Jacksonville, FL, 32224, USA. Odah.Tarek@mayo.edu.
Background And Aims:
Upadacitinib is an oral selective Janus kinase (JAK) inhibitor approved in the United States for ulcerative colitis (UC) and Crohn's disease (CD). However, data regarding its use following prior treatment with the JAK inhibitor tofacitinib is sparse. As such, we aimed to evaluate the effectiveness of upadacitinib therapy following tofacitinib exposure.
Methods:
This is a multicenter retrospective study of patients with confirmed diagnosis of UC or CD who received upadacitinib after prior treatment with tofacitinib. The primary outcome of interest was patient-reported clinical improvement at first follow-up. Secondary outcome included discontinuation of corticosteroids, change in Mayo Endoscopic Score (MES) and change in inflammatory marker levels.
Results:
A total of 31 patients met the inclusion criteria. Following upadacitinib initiation, 80.6% (25/31) of patients had clinical improvement, including 92.3% (24/26) of those with UC and 20% (1/5) of those with CD. Of the patients initially requiring systemic corticosteroid therapy, 80% (12/15) were able to discontinue corticosteroids. Individual mean change of fecal calprotectin was a decrease of 501.5 mcg/g ± 608.6 (P value = 0.01) while C-reactive protein decreased on average by 14.8 mg/L ± 25.3 (P value = 0.02) compared to when patients were on tofacitinib, with significant changes observed in the UC cohort. In patients with UC, individual MES after initiating upadacitinib decreased compared to prior to tofacitinib discontinuation (P value = 0.04).
Conclusion:
Our study demonstrates that upadacitinib therapy in patients with prior tofacitinib exposure is associated with clinical improvement and a decrease in objective markers of inflammation in patients with UC.
Insights
Upadacitinib showed significant clinical improvement and reduced inflammation markers in ulcerative colitis patients previously treated with tofacitinib. This JAK inhibitor offers a viable treatment option for patients with prior Janus kinase inhibitor exposure.
Area of Science:
- Gastroenterology
- Immunology
- Pharmacology
Background:
- Upadacitinib, a Janus kinase (JAK) inhibitor, is approved for ulcerative colitis (UC) and Crohn's disease (CD).
- Limited data exists on upadacitinib's efficacy after prior treatment with another JAK inhibitor, tofacitinib.
- This study addresses the gap in understanding upadacitinib's effectiveness in patients previously exposed to tofacitinib.
Purpose of the Study:
- To evaluate the effectiveness of upadacitinib therapy in patients with UC or CD who previously received tofacitinib.
- To assess clinical improvement, corticosteroid discontinuation, endoscopic scores, and inflammatory marker changes.
- To provide insights into treatment sequencing for inflammatory bowel disease.
Main Methods:
- A multicenter retrospective study involving patients with UC or CD who switched to upadacitinib after tofacitinib treatment.
- Primary outcome: patient-reported clinical improvement at first follow-up.
- Secondary outcomes: corticosteroid discontinuation, changes in Mayo Endoscopic Score (MES), and inflammatory markers (fecal calprotectin, C-reactive protein).
Main Results:
- Eighty-one percent of patients (25/31) experienced clinical improvement on upadacitinib.
- Eighty percent of corticosteroid-dependent patients (12/15) discontinued systemic corticosteroids.
- Significant reductions in fecal calprotectin and C-reactive protein were observed, particularly in the UC cohort. UC patients also showed improved MES.
Conclusions:
- Upadacitinib therapy is associated with clinical improvement in patients with prior tofacitinib exposure.
- Objective markers of inflammation decreased significantly, especially in ulcerative colitis patients.
- Upadacitinib represents a potential therapeutic option for patients with inflammatory bowel disease who have previously been treated with tofacitinib.
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