Comparative short-term efficacy of upadacitinib versus tofacitinib for ulcerative colitis: a 24-week real-world study in Japan

Abstract

Background/aims: Tofacitinib and upadacitinib are small-molecule compounds that inhibit the Janus kinase pathway for the treatment of refractory ulcerative colitis. Only a few reports have compared the efficacy and safety of these 2 drugs in real-world practice. We aimed to show our real-world evidence of these drugs and compare the efficacy and safety profiles in the treatment of ulcerative colitis.

Methods: This study is a single-center retrospective analysis. Patients treated with tofacitinib or upadacitinib at our hospital between June 2018 and January 2024 who were monitored for 24 weeks were included. The primary outcome was steroid-free clinical remission at 24 weeks. Secondary outcomes were response and remission rates at each time point, time series changes in partial Mayo scores and laboratory results, treatment survival at 24 weeks, and the incidence of adverse events.

Results: A total of 68 patients treated with tofacitinib and 34 patients treated with upadacitinib were included. Steroid-free clinical remission rate at 24 weeks was significantly higher in upadacitinib-treated patients than in tofacitinibtreated patients (64.7% vs. 38.2%). The response rates in upadacitinib-treated patients exceeded 60% after 8 weeks of treatment through to 24 weeks, and the rates were higher than those in tofacitinib-treated patients. The incidences of adverse events were 79.4% in upadacitinib-treated patients and 38.2% in tofacitinib-treated patients. The most common adverse event was acne for upadacitinib.

Conclusions: Upadacitinib was more effective than tofacitinib in inducing remission in ulcerative colitis patients. The incidence of adverse events was significantly higher with upadacitinib than tofacitinib.

Keywords: Real-world evidence; Tofacitinib; Ulcerative colitis; Upadacitinib.

Fig. 1.

Flowchart of patients enrolled in this study. pMS, partial Mayo score.

Fig. 2.

Remission and response rates in the whole cohort. (A) Remission rates at 24 weeks of tofacitinib (n=68) and upadacitinib (n=34). Time series data in remission (B) and response (C) rates of tofacitinib (n=68) and upadacitinib (n=34) up to 24 weeks. Statistical significance was analyzed using a Fisher exact test; ^aP<0.05, ^bP<0.01. NS, not significant.

Fig. 3.

Remission and response rates in patients exposed to multiple advanced therapies. (A) Remission rates at 24 weeks of tofacitinib (n=41) and upadacitinib (n=2). Time series data in remission (B) and response (C) rates of tofacitinib (n=41) and upadacitinib (n=27) up to 24 weeks. Statistical significance was analyzed using a Fisher exact test; ^aP<0.01, ^bP<0.001. NS, not significant.

Fig. 4.

Time series data up to 24 weeks. Partial Mayo score (A), stool frequency subscore, (B) and rectal bleeding subscore (C) in patients who had responded tofacitinib (n=29) and upadacitinib (n=26) at 24 weeks. Data are presented as the mean±standard deviation. Statistical significance was analyzed using the Mann-Whitney U test. NS, not significant.

Fig. 5.

Survival curves of patients who continued with either of the treatments up to 24 weeks. Kaplan-Meier curves were drawn using the log-rank (Mantel-Haenszel) test. ^aP<0.05.

Fig. 6.

Adverse event rates during tofacitinib (n=68) and upadacitinib (n=34) therapy. Statistical significance was analyzed using a Fisher exact test; ^aP<0.001.