- 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, Vienna, Austria, 8-11 October.
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 moderate-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 patients.
A previously published, primary analysis of the study that comprised only 451 patients had already shown significant superiority of both 15 and 30 mg upadacitinib dosages over placebo.
These results were reinforced by the final analysis of all patients: 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). 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 its maintenance as well as endoscopic remission, alongside with mucosal improvement and healing (P<0.001 for both dosages and all comparisons with placebo). Prof. Vermeire especially highlighted the significant (P<0.001) reductions in bowel urgency in 53.8% (15 mg) and 66.9% (30 mg) of the patients on the study drug compared with 18.4% on placebo.
“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 maintenance treatment in patients with moderately-to-severely active UC.