Upadacitinib was safe and effective for patients with moderately to severely active ulcerative colitis (UC), according to study findings published in The Lancet.
Researchers conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled clinical program, which included 2 replicate induction studies (U-ACHIEVE substudy 2 [UC1] and U-ACCOMPLISH [UC2]) and a maintenance study (U-ACHIEVE substudy 3 [UC3].
Eligible participants in the induction studies were aged 16 to 75 years with a confirmed diagnosis for UC for at least 90 days and active disease. The patients were randomly assigned 2:1 to receive oral upadacitinib (45 mg once daily) or placebo for 8 weeks. After 8 weeks of induction with upadacitinib 45 mg, participants from the phase 2b U-ACHIEVE substudy 1 and phase 3 UC1 and UC2 studies who achieved clinical response were randomly assigned 1:1:1 to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily in the UC3 maintenance study.
The primary endpoint in the 2 induction studies was clinical remission based on adapted Mayo score at week 8. The primary endpoint in the maintenance study was clinical remission according to adapted Mayo score at week 52.
In UC1, 474 patients were assigned to either upadacitinib 45 mg once daily (n=319; median age, 43 years) or placebo (n=155; median age, 44.5 years) from October 23, 2018, to September 7, 2020. All patients except 1 in the placebo group were included in the intention-to-treat population, and all were included in the safety analysis.
In UC2, 522 patients were randomly assigned to either upadacitinib 45 mg once daily (n=345) or placebo (n=177) from December 6, 2018, to January 14, 2021. Among the cohort, 341 patients (median age, 40 years) in the upadacitinib 45-mg group and 174 patients (median age, 42 years) in the placebo group were included in the intention-to-treat population.
For UC3, 451 patients (21 from the phase 2b study, 278 from UC1, and 152 from UC2) who achieved a clinical response after 8 weeks of upadacitinib 45-mg induction treatment were assigned to upadacitinib 15 mg (n=148; median age, 40 years), upadacitinib 30 mg (n=154; median age, 41 years), and placebo (n=149; median age, 40 years) in the primary analysis population.
In UC1, clinical remission at week 8 was achieved by 26% patients who received upadacitinib vs 5% of patients who received placebo (adjusted treatment difference, 21.6%; 95% CI, 15.8-27.4; P <.0001).
In UC2, 33% of patients receiving upadacitinib achieved clinical remission at week 8 compared with 4% who received placebo (adjusted treatment difference, 29.0%; 95% CI, 23.2-34.7; P <.0001).
In UC3, 42% of patients who received upadacitinib 15 mg once daily, 52% who received upadacitinib 30 mg once daily, and 12% who had placebo achieved clinical remission at week 52 (adjusted treatment difference, 30.7%; 95% CI, 21.7-39.8 for upadacitinib 15 mg vs placebo, P <.0001; and 39.0%; 95% CI, 29.7-48.2 for upadacitinib 30 mg vs placebo, P <.0001).
The proportion of patients who reported adverse events was comparable in the upadacitinib 45-mg group (56%) and placebo group (60%) in UC1. The proportions were higher in the upadacitinib 45-mg group compared with the placebo group in UC2 (53% vs 40%).
The most commonly reported adverse events by patients in UC1 were nasopharyngitis, creatine phosphokinase elevation, and acne. For participants in UC2, the most frequently reported adverse event was acne.
For UC3, the upadacitinib 15-mg group, 30-mg group, and placebo group had similar proportions of reported adverse events. The most common event was worsening of UC.
Study limitations included the restriction to an 8-week induction and 52-week maintenance therapeutic regimen with limited patient exposure, as well as the lack of dose adjustment during maintenance treatment.
“The efficacy and safety data from this programme support the potential of upadacitinib as a promising treatment option in patients with moderately to severely active ulcerative colitis, where despite the currently available treatments, a large unmet need still persists,” the researchers wrote. “As an oral small molecule, upadacitinib might offer various additional benefits to biological therapies including increased treatment adherence and lack of immunogenicity.”
Disclosure: This research was supported by AbbVie. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Danese S, Vermeire S, Zhou W, et al. Upadacitinib as induction and maintenance therapy for moderately to severely active ulcerative colitis: results from three phase 3, multicentre, double-blind, randomised trials. Lancet. 2022;399(10341):2113-2128. doi:10.1016/S0140-6736(22)00581-5