Upadacitinib efficacious and safe as maintenance therapy for UC

Upadacitinib outperformed placebo at all primary and secondary endpoints evaluating maintenance therapy for patients with moderately to severely active ulcerative colitis (UC). The randomised, phase 3 U-ACHIEVE maintenance study evaluated clinical, endoscopic, and histologic endpoints. The observed safety profile of upadacitinib was consistent with prior induction trials.

The oral, selective, reversible JAK inhibitor upadacitinib showed greater efficacy than placebo as induction therapy for patients with UC in two phase 3 trials (U-ACHIEVE [NCT02819635] and U-ACCOMPLISH [NCT03653026]). Clinical responders of the U-ACHIEVE and U-ACCOMPLISH trials (both 45 mg upadacitinib once daily) were enrolled in the U-ACHIEVE maintenance study (n=451). This trial examined the efficacy and safety of upadacitinib as maintenance therapy for patients with moderately to severely active UC [1]. Subjects were randomised 1:1:1 to 15 mg upadacitinib once daily, 30 mg upadacitinib once daily, or placebo. Primary endpoint was the clinical remission per adapted Mayo score at week 52. Results were presented by Dr Remo Panaccione (University of Calgary, Canada).

A significantly greater proportion of upadacitinib receivers achieved clinical remission at week 52 in comparison with placebo receivers (upadacitinib 15 mg, 42%; upadacitinib 30 mg, 52%; placebo, 12%; P<0.001). In addition, maintenance of clinical remission was observed for 59%, 70%, and 22% of the patients in the 15 mg, 30 mg, and placebo groups respectively. Similar outcomes were reported for maintenance of clinical response and maintenance of endoscopic remission.

No new safety issues of upadacitinib emerged in this trial. Adverse events (AEs) were reported in 78.6% (30 mg), 77.7% (15 mg), and 75.8% (placebo) of the patients. Serious AEs were numerically more common in the placebo group (12.8%) than in the experimental conditions (15 mg, 6.8%; 30 mg, 5.8%). The elevation of creatine phosphokinase levels was reported more frequently in upadacitinib receivers, but this did not lead to discontinuations of the trial. Finally, although severe infections were reported more often in the placebo group, herpes zoster infections were exclusively reported in the upadacitinib 15 mg (4.1%) and 30 mg (3.9%) receivers.

1. Panaccione R, et al. Efficacy and safety of upadacitinib maintenance therapy in patients with moderately to severely active ulcerative colitis: results from a randomized phase 3 study. LB11, UEG Week 2021 Virtual Congress, 03–05 October.

 

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Posted on 27 October 20218 April 2024