Final U-ACHIEVE analysis: Upadacitinib well-tolerated, maintains clinical remission in UC
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Key takeaways:
- A greater proportion of patients on upadacitinib 15 mg and 30 mg achieved clinical remission (40.4% and 53.6%) vs. 10.8% on placebo.
- Upadacitinib was well-tolerated with no new safety risks identified.
Patients with moderate to severe ulcerative colitis achieved critical clinical, endoscopic and histological outcomes on maintenance doses of upadacitinib compared with placebo, with no new safety risks reported, according to study results.
“In two identical, double-blind, randomized clinical trials (U-ACHIEVE induction and U-ACCOMPLISH) of patients with moderately to severely active ulcerative colitis and an inadequate response, loss of response or intolerance to conventional or biological therapy, 8 weeks’ double-blind induction therapy with upadacitinib 45 mg once daily led to a significantly greater proportion of patients achieving clinical remission at week 8 vs. placebo and was well-tolerated,” Severine Vermeire, MD, of the department of gastroenterology and hepatology at University Hospital Leuven, and colleagues wrote in The Lancet Gastroenterology & Hepatology.
In the phase 3 U-ACHIEVE maintenance study, 681 patients with a clinical response to once-daily upadacitinib 45 mg from the U-ACHIEVE induction (n = 319), U-ACCOMPLISH (n = 341) and phase 2b induction (n = 21) trials were randomized to once-daily placebo (n = 223), upadacitinib 15 mg (n = 225) or upadacitinib 30 mg (n = 233) for 52 weeks. Participants who received at least one dose of the study drug were included in the 8-week intention-to-treat efficacy population. In addition, 746 patients (552.9 patient-years of exposure) who achieved clinical response after 8 weeks of once-daily upadacitinib 45 mg were included in the 8-week induction responder safety population.
The primary outcome was clinical remission per adapted Mayo score, defined as a stool frequency subscore of no more than 1 and not greater than baseline; a rectal bleeding score of zero; and an endoscopic subscore of no more than 1 without friability.
Researchers reported a significantly greater proportion of patients achieved clinical remission at week 52 in the upadacitinib 15 mg (40.4%) and 30 mg (53.6%) groups compared with placebo (10.8%).
Similarly, more patients in the 15 mg and 30 mg upadacitinib groups achieved endoscopic (48.5% and 63.3%, respectively, vs. 14.1%) and histologic-endoscopic improvement (40.5% and 56% vs. 12.3%), in addition to maintaining endoscopic improvement (61.2% and 71% vs. 18.4%).
“Across all analyzed efficacy endpoints, outcomes were numerically better with upadacitinib 30 mg once daily than upadacitinib 15 mg once daily,” Vermeire and colleagues noted.
According to the safety analysis, nine patients on placebo experienced worsening of UC, and two patients on upadacitinib 30 mg developed COVID-19 pneumonia and cryptococcal pneumonia. Compared with placebo, patients in the treatment group experienced higher exposure-adjusted event rates of herpes zoster, hepatic disorders, elevation in creatine phosphokinase and neutropenia.
Less than 1% of patients in the placebo and upadacitinib 30 mg groups experienced an adjudicated major adverse cardiovascular event, and 1% of patients in both upadacitinib dosage groups experienced venous thromboembolic events. Researchers noted all of these events occurred among patients with known risk factors.
“Both upadacitinib maintenance doses were significantly more efficacious than placebo for achieving important clinical, endoscopic and histological outcomes while maintaining an acceptable safety profile with no new safety risks in the full trial population over 52 weeks,” Vermeire and colleagues concluded. “The favorable benefit-risk profile of both maintenance doses in this analysis was consistent with that observed in the primary analysis of a smaller patient population.”
They continued: “Overall, these findings support the use of upadacitinib as a therapeutic option for treating patients with moderately to severely active ulcerative colitis, for whom a large unmet need persists.”
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