Long-term upadacitinib data reassuring for patients with UC

Upadacitinib was associated with high clinical and endoscopic remission rates in patients with moderately to severely active ulcerative colitis (UC) who had received up to 4 years of treatment with this agent. The extended safety data did not reveal novel safety risks for this JAK inhibitor in the UC population.

“Upadacitinib is an approved agent for patients with moderately to severely active UC,” stated Prof. Remo Panaccione (University of Calgary, Canada) [1]. “Still, it is important to see how this agent performs in the long term.” The U-ACTIVATE trial (NCT03006068) was designed to evaluate the efficacy and safety of upadacitinib in UC over 288 weeks. Participants who responded to 8 weeks of upadacitinib induction therapy were eligible to enter the U-ACHIEVE maintenance study (n=756). After 52 weeks of maintenance therapy, participants could continue on their maintenance dose in the long-term extension study if they were in clinical remission and had the option to receive a higher dose if they were not in clinical remission. Prof. Panaccione presented the findings at week 144 of the long-term extension study (n=401).

At the time of analysis, 60.6% of the participants in the 15 mg group and 51.3% of those in the 30 mg group were in clinical remission per adapted Mayo score, as assessed by modified non-responder imputation. Furthermore, maintenance of clinical remission throughout 144 was observed in 73.5% and 60.3% of the participants in the 15 mg and 30 mg arms, respectively. Prof. Panaccione also mentioned that 43.5% and 44.2% of the participants in the 15 mg and 30 mg arms were in endoscopic remission and that 55.6% and 59.2% had maintained endoscopic remission over the course of the long-term extension study (see Figure).

Figure: Proportion of patients achieving endoscopic endpoints at long-term extension week 144 [1]



AO, as observed; mNRI, modified non-responder imputation; QD, once daily; UPA, upadacitinib.

“Finally, both doses of upadacitinib were well-tolerated over a long period,” Prof. Panaccione continued. “There were 5 opportunistic infections, 7 malignancies [excluding non-melanoma skin cancer], and 2 cases of major adverse cardiovascular event (MACE). Discontinuation due to adverse events was reported for 48 participants.”

Participants achieved and maintained important clinical and endoscopic outcomes after 4 years of treatment with upadacitinib. The favourable long-term safety data confirm the positive benefit-risk profile of this agent for patients with UC.

1. Panaccione R, et al. Efficacy and safety of upadacitinib after 4 years of treatment in patients with moderately to severely active ulcerative colitis: interim long-term data from the phase 3 study (U-ACTIVATE). DOP02, 20th Congress of ECCO, 19–22 February 2025, Berlin, Germany.

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Posted on 8 April 20258 April 2025