Upadacitinib after tofacitinib in ulcerative colitis
Article information
Recently, the advent of Janus kinase (JAK) inhibitors has rapidly changed the treatment landscape of ulcerative colitis (UC) [1]. Upadacitinib, a selective JAK1 inhibitor, has emerged as a promising option following the success and the limitations of tofacitinib, a pan-JAK inhibitor. However, whether upadacitinib shows efficacy in patients previously exposed to tofacitinib has remained an important unanswered question.
In this issue of Intestinal Research, Gilmore et al. [2] reported a multicenter Australian real-world cohort study. Here, the authors provide robust evidence that upadacitinib is not only effective as an induction agent for moderate-to-severe UC but also performs well in patients with prior tofacitinib exposure. Their retrospective analysis of 152 patients across 13 centers found clinical remission rates of 79% at week 8 and 84% at week 16—figures that surpass those reported in phase 3 trials [3]. Importantly, remission was comparably high in both tofacitinib-naive and -experienced groups by week 16, suggesting that upadacitinib has therapeutic value even after tofacitinib failure or intolerance.
There are several aspects of this study drawing close attention. First, the inclusion of patients with isolated proctitis—a population often excluded from clinical trials—adds valuable real-world relevance. Therefore, this study indicates the efficacy of upadacitinib in a wider spectrum of patients. Second, the study utilized intestinal ultrasound (IUS) to demonstrate transmural healing, a surrogate marker for deeper and more durable remission. By week 16, 81% of patients with serial IUS data achieved transmural remission, with complete concordance observed with endoscopic and clinical indices. This supports the emerging role of IUS in both assessing and predicting treatment response in UC [4].
One of the most reassuring findings is the safety profile. Despite a high induction dose of 45 mg, adverse events were generally mild and consistent with previous reports [5]. The absence of serious thromboembolic events or malignancy during the 16-week window adds confidence, although longer follow-up is necessary.
Among patients with active disease at baseline, those with prior tofacitinib exposure had lower remission rates at week 8 compared to tofacitinib-naive patients. This suggests a potentially slower onset of action or a more refractory disease phenotype. Clinically, this raises important considerations for managing acute severe UC in patients with prior JAK inhibitor exposure—an area still lacking in robust guidance.
This study fills a critical gap in real-world evidence and broadens the scope of upadacitinib’s utility in UC, particularly in a treatment-experienced population. The efficacy of upadacitinib after tofacitinib has been supported by other studies as well showing similar results [6,7]. It also strengthens the rationale for adopting treat-to-target strategies that integrate noninvasive tools like IUS. Future prospective studies with longer follow-up will be instrumental in confirming durability of response and long-term safety, particularly in high-risk cohorts.
However, this study has several limitations that should be considered when interpreting the findings. Because of the retrospective design, there was recall and selection bias. Lack of a control group limits the ability to draw causal inferences. As this study focused on the results of induction, it could not evaluate the efficacy and safety of upadacitinib during the maintenance of remission after tofacitinib failure. Finally, due to the small sample size, rare adverse events such as deep vein thrombosis, malignancies or major adverse cardiovascular events may not be detected in this cohort.
In summary, Gilmore et al. [2] provide convincing real-world evidence that upadacitinib is not only effective in a broad range of UC patients including those with prior tofacitinib use but also safe and rapid-acting. These data will undoubtedly influence how we sequence therapies and personalize treatment in the era of precision inflammatory bowel disease care.
Notes
Funding Source
The authors received no financial support for the research, authorship, and/or publication of this article.
Conflict of Interest
Kim ES is an editorial board member of the journal but was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.
Data Availability Statement
Not applicable.
Author Contributions
Writing and approval of the final manuscript: Cho HJ, Kim ES.