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A significantly higher proportion of patients with moderate to severe ulcerative colitis who responded well to upadacitinib (Rinvoq) induction achieved clinical remission with maintenance therapy compared to those who switched to placebo, a researcher reported in a randomized phase III trial.

More patients randomized to receive upadacitinib at either 30 mg or 15 mg doses achieved clinical remission at 52 weeks compared to those randomized to placebo (52% and 42% vs 12%, P<0.001 for both, respectively), according to Peter Higgins, MD, PhD, of the University of Michigan in Ann Arbor, in a late-breaking presentation at the American College of Gastroenterology virtual meeting.

The trial also achieved its secondary endpoints at week 52, including P<0.001 for all):

• Maintenance of clinical remission (70% for 30 mg and 59% for 15 mg vs 22% for placebo)
• Corticosteroid-free clinical remission (68% and 57% vs 22%, respectively)
• Endoscopic improvement (62% and 49% vs 15%)
• Maintenance of endoscopic improvement (70% and 62% vs 19%)
• Endoscopic remission (26% and 24% vs 6%)
• Maintenance of clinical response (77% and 63% vs 19%)
• Histologic endoscopic mucosal improvement (49% and 35% vs 12%)

"Endoscopic remission is a really tough endpoint to hit, truly," Higgins said. "I just think in my clinical practice how many times the pathologist says there is no evidence of histologic UC [ulcerative colitis], I see it 20-25% of the time, but it's a tough endpoint."

The reversible and selective JAK inhibitor upadacitinib was originally approved by the FDA to treat moderate to severe rheumatoid arthritis for adults, but has been investigated for ulcerative colitis and other inflammatory conditions.

"The results are compelling," said Miguel Regueiro, MD, Chair of Cleveland Clinic's Digestive Disease & Surgery Institute in Ohio, who was not involved in this study. "The efficacy rates were realized even for patients who had previously failed anti-TNF [tumor necrosis factor] therapy -- this is significant and often not realized in other medication studies."

"This means that upadacitinib will represent an oral medication with high efficacy and safety for the treatment of ulcerative colitis," Regueiro added.

For this study, Higgins and colleagues evaluated 451 patients previously enrolled in the induction trials, and , who achieved clinical response from 45 mg of upadacitinib given once daily and re-enrolled them in the U-ACHIEVE Maintenance study. This double-blind trial randomized patients 1:1:1 to receive 15 mg of upadacitinib, 30 mg of upadacitinib, or placebo once daily for 52 weeks.

Achieving clinical remission by week 52 was the primary endpoint. Patients were stratified based on baseline corticosteroid use, clinical remission, and prior failed biologics.

Participants were a median age of 40-41 years, 36-43% were women and 62-66% were white. Mean duration of disease for most patients was 8-9 years.

Higgins' team noted that both dosages of the drug were "safe and effective as maintenance treatment [...] for all clinical, endoscopic and histologic endpoints," adding that patients on the 30 mg dose of the drug had approximately a 10% better response for most endpoints compared to patients on the 15 mg dose.

Similar adverse event rates, including those resulting in drug discontinuation were observed for both upadacitinib groups, but were higher for placebo patients.

Higgins' group found that 1.3% of patients in the 30 mg intervention group had venous thromboembolism. (In September, FDA required new warnings on upadacitinib and other JAK inhibitors due to increased risk for serious heart-related events.)

When asked about the venous thromboembolism adverse events, Higgins said that one of the events was in a patient with COVID-pneumonia and the other patient's "only risk factor was obesity."

Adverse events reported by 5% or more of patients in the treatment group included nasopharyngitis, elevation of creatine phosphokinase, ulcerative colitis exacerbation, upper respiratory tract infection, and arthralgia. Of those, elevation of creatine phosphokinase had the greatest percentage difference between intervention and placebo groups (6.1%-8.4% vs 2.0%, respectively).

The analysis had several limitations, including generalizability and follow-up duration.

"I think this one [drug] is substantially more potent than our previous JAK inhibitors and hopefully we'll see more development on this front," Higgins said.

As far as next steps in research, Higgins told 番茄社区app that researchers plan to test upadacitinib on severe ulcerative colitis inpatients, as well as "testing whether Shingrix vaccine can prevent shingles in patients on [upadacitinib], and testing of combination therapy with risankizumab."

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