Response to Upadacitinib in Patients with Inflammatory Bowel Disease Previously Treated with Tofacitinib

Dig Dis Sci. 2024 Oct;69(10):3911-3919. doi: 10.1007/s10620-024-08630-3. Epub 2024 Sep 9.

Abstract

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.

Keywords: Crohn’s disease; Inflammatory bowel disease; Tofacitinib; Ulcerative colitis; Upadacitinib.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Colitis, Ulcerative* / drug therapy
  • Crohn Disease* / drug therapy
  • Female
  • Heterocyclic Compounds, 3-Ring* / therapeutic use
  • Humans
  • Janus Kinase Inhibitors* / therapeutic use
  • Leukocyte L1 Antigen Complex / analysis
  • Leukocyte L1 Antigen Complex / metabolism
  • Male
  • Middle Aged
  • Piperidines* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome

Substances

  • upadacitinib
  • tofacitinib
  • Piperidines
  • Heterocyclic Compounds, 3-Ring
  • Pyrimidines
  • Janus Kinase Inhibitors
  • Leukocyte L1 Antigen Complex