Positive topline results were announced from a phase 3 maintenance study evaluating upadacitinib in adults with moderate to severe Crohn disease who had an inadequate response or were intolerant to a conventional or biologic therapy.
The randomized, double-blind, placebo-controlled U-ENDURE maintenance study (ClinicalTrials.gov Identifier: NCT03345823) included adults with moderate to severe Crohn disease who responded to upadacitinib induction treatment in the U-EXCEED (ClinicalTrials.gov Identifier: NCT03345836) and U-EXCEL (ClinicalTrials.gov Identifier: NCT03345849) studies.
In U-ENDURE, patients were randomly assigned to receive upadacitinib 15mg, 30mg, or placebo once daily for 52 weeks. The primary endpoints were the proportion of patients with clinical remission per Crohn Disease Activity Index (defined as CDAI <150) or by stool frequency and abdominal pain score (SF/AP), and endoscopic response (defined as a decrease in Simple Endoscopic Score for Crohn Disease), at week 52.
Findings showed that a significantly higher proportion of patients treated with upadacitinib 15mg and 30mg met the following primary and secondary endpoints at week 52 compared with those treated with placebo, respectively:
- Clinical remission per CDAI: 37% and 48% vs 15% (P <.0001).
- Clinical remission per SF/AP: 36% and 46% vs 14% (P <.0001).
- Endoscopic response: 28% and 40% vs 7% (P <.0001).
- Endoscopic remission: 19% and 29% vs 5% (P <.0001).
Among patients taking corticosteroids at baseline, a significantly higher proportion of patients treated with upadacitinib 15mg and 30mg achieved corticosteroid-free clinical remission per CDAI and per SF/AP at week 52 compared with placebo.
“Symptomatic relief as well as healing of the intestinal mucosa in Crohn disease are important long-term treatment targets which may be associated with slowing disease progression and better quality of life for patients,” said Julian Panes, Emeritus Professor of Medicine and the Chief of the IBD Unit at Hospital Clínic de Barcelona and lead study investigator. “These results are encouraging and would be particularly important for patients who have not found relief with other conventional or biologic treatment options.”
The most common adverse events reported with upadacitinib were exacerbation of Crohn disease, arthralgia and pyrexia. The rates of serious adverse events and serious infection events per 100 patient years for the placebo, upadacitinib 15mg, and upadacitinib 30mg arms were 37.4/8.4, 25/6.1, and 21.0/7.8, respectively. There were no reported adjudicated thrombotic events or major adverse cardiovascular events reported in any treatment arm. As for malignancies (excluding nonmelanoma skin cancer), there was 1 event in the upadacitinib 15mg arm, 2 events in the upadacitinib 30mg arm, and no events in the placebo arm.
Upadacitinib, a selective and reversible JAK inhibitor, is currently marketed under the brand name Rinvoq and is approved for the treatment of active psoriatic arthritis, active ankylosing spondylitis, moderately to severely active rheumatoid arthritis, moderate to severe atopic dermatitis, and moderately to severely active ulcerative colitis.
Upadacitinib (Rinvoq®) achieved clinical remission and endoscopic response at one year in phase 3 maintenance study in patients with Crohn’s disease. News release. AbbVie. Accessed May 11, 2022. https://www.prnewswire.com/news-releases/upadacitinib-rinvoq-achieved-clinical-remission-and-endoscopic-response-at-one-year-in-phase-3-maintenance-study-in-patients-with-crohns-disease-301544975.html