Sustained maintenance results with upadacitinib in UC

Final results of the U-ACHIEVE Maintenance trial demonstrated superiority of upadacitinib over placebo in disease control of ulcerative colitis (UC), along with a favourable safety analysis. The primary and key secondary endpoints that comprised clinical, histological, and patient-reported outcomes were met.

Moderate-to-severe UC induction and maintenance therapy with the selective, JAK1-inhibiting, small molecule upadacitinib has been approved by the US FDA and as of recently also in Europe. Top abstract prize awardee Prof. Séverine Vermeire (University Hospital Leuven, Belgium) presented the final results from the U-ACHIEVE Maintenance study (NCT02819635) [1]. Included were 681 patients between 16 and 75 years of age with moderately to severely active UC who had responded to a 45 mg upadacitinib induction therapy within the 2 identical trials U-ACCOMPLISH (NCT03653026) and U-ACHIEVE Induction (NCT02819635). For U-ACHIEVE Maintenance, these responders were re-randomised to 3 study arms: placebo, upadacitinib 15 mg, or upadacitinib 30 mg. Clinical remission in the adapted Mayo score, including rectal bleeding, stool frequency, and endoscopic results, was the primary endpoint. Among the secondary endpoints were maintenance of response, steroid-free remission, and patient-reported outcomes.

The mean age at baseline ranged from 41.7 to 43.0 years, 35.1% to 44.8% were women, and disease duration was around 8 years. Prior treatment with at least 1 biologic agent was observed in 45.9% to 48.0% of participants.

As previously published, the primary analysis of the study that comprised the first 451 participants showed significant superiority of both 15 and 30 mg upadacitinib dosages over placebo [2]. These results were reinforced by the final analysis of all participants: 40.4% on 15 mg and 53.6% on 30 mg of upadacitinib reached clinical remission versus 10.8% on placebo (P<0.001 for both comparisons) [2]. Positive secondary endpoints for the 15 mg and the 30 mg regimens of upadacitinib included maintenance of clinical response (65.6% and 77.5% vs 21.5%; both P<0.001) and corticosteroid-free clinical remission (52.3% and 64.6% vs 18.8%; both P<0.001). Furthermore, upadacitinib achieved significant better results for endoscopic improvement and maintenance, endoscopic remission, and mucosal improvement and healing (P<0.001 for both dosages and all comparisons with placebo). Prof. Vermeire especially highlighted the significant reductions in bowel urgency in 53.8% (15 mg) and 66.9% (30 mg) of the participants on the study drug compared with 18.4% on placebo (both P<0.001).

“Both of the doses were well tolerated – we did not observe any new safety signals compared with the smaller primary analysis or other non-UC indications,” Prof. Vermeire summarised the safety assessment. This final analysis supports the favourable benefit-risk profile of upadacitinib as a maintenance treatment in patients with moderately to severely active UC.

1. Vermeire S. Efficacy and safety of upadacitinib maintenance therapy in patients with moderately to severely active ulcerative colitis: final results from the phase 3 U-ACHIEVE Maintenance study. OP001, UEG Week 2022, 8–11 October, Vienna, Austria.
2. Danese S, et al. Lancet. 2022;399(10341):2113–2128.

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Posted on 1 December, 2022