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A higher daily dose of upadacitinib (Rinvoq) was associated with less severe disease and longer clinical remission for ulcerative colitis patients who responded to upadacitinib induction at 8 weeks, a post-hoc analysis of the phase III U-ACHIEVE maintenance trial found.

An absolute 19.7% more patients ended with less severe disease after 52 weeks with a 30-mg versus 15-mg daily dose of upadacitinib, which included 10.5% more of those with mild disease and 9.2% more among those with moderate disease, according to Brian Feagan, MD, of Western University in London, Canada.

An area under the curve analysis showed the 30-mg group was in clinical remission for nearly 1 month more per year than the 15-mg group (34.4 vs 30.5 vs 15.8 weeks for placebo), he said in a presentation at the American College of Gastroenterology annual meeting in Charlotte, North Carolina.

"This may be an encouraging treatment strategy for patients with ulcerative colitis," commented Alessandra Gasior, DO, of the Ohio State University Wexner Medical Center in Columbus.

In a sensitivity analysis of those younger than 65 years (411 of the 451 patients), the higher dose reduced disease severity for an absolute 26% more patients than did the 15 mg dose over the 52 weeks, including an absolute 14% more with mild disease and 12% more with moderate disease.

"This study demonstrates the important clinical benefit of high-dose upadacitinib as maintenance therapy, and we've shown a relevant subgroup in patients younger than age 65 where this effect, if anything, was slightly greater," Feagan concluded at the meeting. He added that patients older than age 65 might not benefit as much because of being prone to more infection and cardiovascular susceptibilities.

For patients with active ulcerative colitis, the reversible and selective JAK inhibitor has been successful in inducing and maintaining clinical response and remission.

The primary analysis of the U-ACHIEVE maintenance study found more clinical remissions with the two upadacitinib doses for moderate to severe ulcerative colitis, compared with placebo. Researchers have suggested the benefits of treatment may potentially increase with higher doses.

"However, the relative benefits of the 30-mg versus low dose, 15-mg, doses of upadacitinib as maintenance therapy remains to be established," said Feagan.

For this post-hoc study, researchers examined data on 451 patients with ulcerative colitis from the maintenance trial, which re-randomized patients from the U-ACHIEVE and U-ACCOMPLISH induction trials to receive a daily maintenance dose of 15 mg (n=148) or 30 mg (n=154) of upadacitinib or placebo (n=149) for 52 weeks. Included were those who achieved clinical response following 8 weeks of induction with a daily dose of 45 mg of upadacitinib.

Disease activity was assessed by the adapted Mayo score, with mild disease indicated by a score below 5, moderate by a score of 5 to 7, and severe defined by scores over 7.

Across all groups, at least 91% experienced mild disease, including those below age 65. None had severe disease at the outset of maintenance treatment.

At every time point through the 52-weeks of follow-up, more than 64% of the 30-mg group sustained clinical remission as defined by the partial adapted Mayo score.

"The placebo group separates out at as early as 4 weeks," Feagan said. "The two active-therapy groups over time were at approximately 10% difference in remission rates by partial Mayo score favoring the high dose, with separation between the two at approximately 10 weeks."

Among participants younger than age 65, at least 62% of the 30-mg group sustained clinical remission at every point during the year of follow-up. These younger patients gained an additional 4.2 weeks of clinical remission on average with the higher versus lower dose.

"One hundred and fifty patients per group is probably not adequate to assess long-term safety, that will be the subject of follow-up extension studies and registries," Feagan acknowledged.

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