A phase 3 study evaluating upadacitinib for the maintenance treatment of adults with moderately to severely active ulcerative colitis met its primary and all secondary endpoints.
The multicenter, randomized, double-blind, placebo-controlled maintenance study (ClinicalTrials.gov Identifier: NCT02819635) evaluated upadacitinib in 451 adults with moderately to severely active ulcerative colitis. Following an 8-week induction treatment period of upadacitinib 45mg once daily, 746 patients who achieved clinical response were randomly assigned to receive upadacitinib 15mg (n=148), 30mg (n=154), or placebo (n=149) for an additional 52 weeks.
The primary endpoint was clinical remission (per Adapted Mayo Score) at week 52. Secondary endpoints included achievement of endoscopic improvement (defined as endoscopic subscore of of 1 or less), histologic-endoscopic mucosal improvement (HEMI; defined as an endoscopic subscore of 1 or less and Geboes score of 3.1 or less), and corticosteroid-free clinical remission (defined as clinical remission and corticosteroid free for 90 or more days prior to week 52).
Findings demonstrated that a significantly greater proportion of patients treated with upadacitinib 15mg and 30mg achieved clinical remission at week 52 compared with those receiving placebo (42% and 52% vs 12%, respectively; P <.001). Moreover, the study met all secondary endpoints with a greater proportion of patients treated with upadacitinib 15mg and 30mg achieving the following results at week 52 compared with placebo, respectively:
- Endoscopic improvement: 49% and 62% vs 14% (P <.001);
- HEMI: 35% and 49% vs 12% (P <.001);
- Corticosteroid-free clinical remission: 57% and 68% vs 22% (P <.001).
The safety profile of upadacitinib was consistent with that observed in previous studies across indications, including previously reported phase 3 induction studies for ulcerative colitis. There were no new safety risks identified. The most common treatment-emergent adverse reactions observed during the maintenance period were nasopharyngitis, exacerbation of ulcerative colitis, and increased blood creatinine phosphokinase.
Upadacitinib, a selective and reversible Janus kinase (JAK) inhibitor, is marketed under the trade name Rinvoq and is currently approved for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to methotrexate.
Upadacitinib (Rinvoq®) met the primary and all secondary endpoints in the 52-week phase 3 maintenance study in ulcerative colitis patients. [press release]. North Chicago, IL: AbbVie; June 29, 2021.