Ramona Vladea, PhD

New data continues to show the benefit of upadacitinib in the treatment of adult patients with ulcerative colitis.

New data from a phase 3 trial shows the efficacy and safety of upadacitinib in induction and maintenance therapy in patients with moderate to severely active ulcerative colitis.

A team, led by Ramona Vladea, PhD, AbbVie, presented new data during the 2022 American College of Gastroenterology (ACG) Annual Meeting in Charlotte on the 52 week efficacy and safety benefit-risk assessment of upadacitinib 15 mg and 30 mg compared to placebo.

In the study, the investigators re-randomized 681 patients with a clinical response after 8 weeks of upadacitinib 45 mg once daily induction treatment in the U-ACHIEVE trial or the U-ACCOMPLISH trial to the U-ACHIEVE maintenance trial.

Each participant in the maintenance trial was treated with either upadacitinib 15 mg once daily (n = 225), upadacitinib 30 mg once daily (n = 223), or placebo (n = 223).

The investigators sought efficacy outcomes of point estimates and 95% confidence intervals of placebo adjusted treatment effect.

They also sought primary endpoints of clinical remission at week 52.

In the risk analysis, the investigators evaluated exposure-adjusted event rates per 100 patient-years of selected adverse events of special interest.

Treatment Effect

Point estimates of placebo-adjusted treatment effect was 30.1% (95% CI, 22.7-37.4) for the upadacitinib 15 mg group. The point estimates of placebo-adjusted treatment effect was 42.9% (95% CI, 355.4-50.4) for the upadacitinib 30 mg cohort (P <0.001 for both).

However, there were significant differences across secondary endpoints for either upadacitinib doses or placebo (all P <0.001).

Infections

The rate of serious infections was 5.9 events per 100 person-years in the placebo group, compared to 5.0 events in the upadacitinib 15 mg cohort and 3.2 upadacitinib 30 mg group. There were also no events of herpes zoster reported in the placebo group. However, the rates of upadacitinib 15 mg was 6.0 and the rate of upadacitinib 30 mg was 7.3 events per 100 person years.

The rates of malignancy, excluding non-melanoma skin cancer, was 0.7 events per 100 person-years with placebo, compared to 0.5 and 0.9 with upadacitinib 15 mg and upadacitinib 30 mg, respectively.

The rates of non-melanoma skin cancer was 1.4 events per 100 person-years in the upadacitinib 30 mg group, but no cases reported in the upadacitinib 15 mg group or the placebo cohort.

Adjudicated venous thromboembolic events were low in patients treated with upadacitinib and no cases reported in the placebo group.

Adjudicated major adverse cardiovascular events were low in both the placebo and upadacitinib 30 mg groups, with none found in the upadacitinib 15 mg cohort.

“Response rates were significantly greater with upadacitinib 15mg and upadacitinib 30mg versus placebo across endpoints assessed. Upadacitinib doses were well tolerated,” the authors wrote. “Rates of herpes zoster and creatine phosphokinase elevation, known safety signals of JAK inhibitors, were dose-dependent. The data suggest that upadacitinib 15mg and upadacitinib 30mg once daily have a favorable benefit–risk profile after 52 weeks maintenance therapy. The safety of upadacitinib continues to be monitored in long-term extension study.”

The study, “A0329 - Benefit–Risk Assessment of Upadacitinib Treatment in Patients With Moderately to Severely Active Ulcerative Colitis,” was published online by ACG.