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A 30 mg dose of upadacitinib led to a 1 month longer clinical remission and approximately 20% of patients had less severe disease at 52 weeks, when compared with a 15 mg dose for patients with active ulcerative colitis.
Treatment with a 30 mg daily maintenance dose of upadacitinib (Rinvoq) led to 3.8 additional weeks of clinical remission versus a 15 mg dose of the JAK inhibitor for patients with active ulcerative colitis (UC), according to 52-week results from the U-ACHIEVE phase 3 maintenance trial presented at the American College of Gastroenterology (ACG) 2022 Annual Scientific Meeting in Charlotte, NC.
At the end of the 52-week maintenance period, 19.7% of patients had less severe disease in the 30-mg upadacitinib arm compared with the 15-mg arm (P <.0001). Both arms significantly outperformed placebo. These findings were even more pronounced in patients who were below the age of 65 years. In this group, 26.1% of patients had less severe disease at 52 weeks with the 30-mg versus the 15-mg dose of upadacitinib (P <.0001). Clinical remission in this population lasted 4.2 weeks longer with the higher dose.
"This study demonstrates the important clinical benefit of high-dose upadacitinib as maintenance treatment in UC, especially among patients younger than 65 old, where the effect was even greater," lead investigator Brian G. Feagan, MD, Alimentiv, Inc, Western University, London, ON, Canada, said during a presentation of the results. "Over the 52-week maintenance period, patients in the 30 mg group were in clinical remission, based on the Partial Adapted Mayo score, for approximately 1 additional month per year compared with patients in the upadacitinib 15 mg group."
Based on earlier findings from the U-ACHIEVE study, in addition to results from the phase 3 U-ACCOMPLISH study, in March 2022 the FDA approved upadacitinib as a treatment for patients with moderately to severely active UC who had an inadequate response or intolerance to one or more TNF alpha blocker. This added to several other indications for the JAK inhibitor, including a recent October 21, 2022, approval for upadacitinib in adults with difficult-to-treat active non-radiographic axial spondyloarthritis.
For the phase 3 study, patients received an 8-week induction dose of 45-mg upadacitinib. Those who responded were rerandomized 1:1:1 to receive upadacitinib at 15 mg (n = 148), 30 mg (n = 154), or placebo (n = 149). At baseline for the maintenance trial, the severity of disease was similar across each group, with approximately 92% of patients having mild disease and 8% with moderate disease. There were no patients with severe UC at maintenance baseline. These characteristics were similar for those in the total population and those less than 65 years of age. At baseline, approximately 65% of patients were in clinical remission per partial adapted Mayo score.
Across the overall population after 52 weeks of follow up, 74% of patients treated with 30-mg upadacitinib daily had mild disease, 15.6% had moderate disease, and 9.7% had severe UC. With the 15-mg upadacitinib dose, 63.5% of patients had mild disease, 16.9% had moderate disease, and 18.9% had severe disease. Both upadacitinib arms outperformed placebo, wherein 22.8% of patients with mild disease at the end of the maintenance period, and 47% and 30.2% had moderate and severe UC, respectively.
In the total population, clinical remissions were sustained in 64.5% of patients treated with 30-mg maintenance upadacitinib compared with 57.4% of those receiving the 15 mg dose. With placebo, this rate was just 17.5%. Clinical Remissions lasted 30.5 weeks with the 15 mg dose and 34.4 weeks with the 30 mg dose of upadacitinib. In the placebo group, clinical remission lasted just 15.8 weeks.
In those below the age of 65 years, the 30 mg upadacitinib dose resulted in mild disease at 52 weeks for 75.5% of patients. There were 15.8% of patients with moderate disease and 8.6% with severe. In the 15 mg dose arm, there were 61.5% of patients with mild disease, 17.0% with moderate, and 20.7% with severe UC. In the placebo group, 21.9% had mild disease, 47.4% had moderate, and 30.7% had severe UC.
In patients below the age of 65, at 52 weeks 64.1% continued to have a clinical remission with 30-mg upadacitinib. In the 15-mg arm, 54.1% of patients continued to be in clinical remission at 52 weeks. In the placebo group, just 14.7% were in clinical remission. In the 15-mg dose group, the mean duration of clinical remission was 30.4 weeks compared with 34.6 weeks with the 30-mg dose. In the placebo group, clinical remission lasted a mean of 16 weeks.
"There were about 2.5 times more patients in the lower dose with severe disease at 52 weeks, indicating superiority of the larger dose," Feagan said. "There were not discernible differences in safety but there were only about 150 patients in each arm, so there is not enough to assess long-term safety."
The oral abstract, “Benefits of high versus low dose upadacitinib as maintenance treatment in ulcerative colitis patients who were responders to 8-week induction with upadacitinib: Results from the U-ACHIEVE phase 3 maintenance trial,” was presented at ACG 2022.