– Significantly more upadacitinib-treated (15 mg or 30 mg, once daily) patients achieved the primary endpoint of clinical remission (per Adapted Mayo Score) compared to patients on placebo at one-year (week 52) (p<0.001)[1]
– All secondary endpoints were met, including the achievement of endoscopic improvement, HEMI and corticosteroid-free clinical remission at one-year (p<0.001)[1]
– Safety results were consistent with the previous Phase 3 induction studies and the known safety profile of upadacitinib, with no new safety risks observed[1-6]
– Upadacitinib, a selective and reversible JAK inhibitor discovered and developed by AbbVie, is being studied as an oral therapy for moderate to severe ulcerative colitis and several other immune-mediated inflammatory diseases[1,7-14]
NORTH CHICAGO, Ill., June 29, 2021 /PRNewswire/ — AbbVie (NYSE: ABBV) today announced that upadacitinib (15 mg or 30 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) and all secondary endpoints at one-year (week 52) in the Phase 3 ulcerative colitis maintenance study.1 Significantly more upadacitinib-treated patients achieved clinical remission at week 52 compared to placebo (15 mg: 42 percent and 30 mg: 52 percent versus placebo: 12 percent; p<0.001).1
“Ulcerative colitis is a disease with unpredictable symptoms and frequent flares, which can make daily life challenging,” said Michael Severino, M.D., vice chairman and president, AbbVie. “We are encouraged by these results that demonstrate upadacitinib’s potential as a treatment option for patients with moderate to severe ulcerative colitis.”
In this study, adults with moderate to severe ulcerative colitis who achieved a clinical response (per Adapted Mayo Score) following an 8-week study period of once-daily upadacitinib (45 mg) induction treatment were re-randomized to receive upadacitinib 15 mg, upadacitinib 30 mg or placebo for an additional 52 weeks.1
All secondary endpoints were met, including the achievement of endoscopic improvement, histologic-endoscopic mucosal improvement (HEMI) and corticosteroid-free clinical remission at week 52.1 49 percent of patients treated with upadacitinib 15 mg and 62 percent of patients treated with upadacitinib 30 mg achieved endoscopic improvement at 52 weeks versus 14 percent of patients in the placebo group (p<0.001).1 In addition, 35 percent of patients on upadacitinib 15 mg and 49 percent of patients on upadacitinib 30 mg achieved HEMI compared to 12 percent of patients in the placebo group (p<0.001).1 Of patients who were in remission at the completion of the 8-week induction studies, corticosteroid-free remission was achieved in 57 percent of patients in the upadacitinib 15 mg group and 68 percent of patients in the upadacitinib 30 mg group compared to 22 percent of patients in the placebo group (p<0.001).1
| Phase 3 Maintenance Efficacy Results at Week 52*,1 | |||
| Upadacitinib 15 mg, once daily (n=148) | Upadacitinib 30 mg, once daily (n=154) | Placebo (n=149) | |
| Clinical remissiona | 42% | 52% | 12% |
| Endoscopic improvementb | 49% | 62% | 14% |
| HEMIc | 35% | 49% | 12% |
| Corticosteroid-free clinical remissiond | 57% | 68% | 22% |
| *Primary endpoint was clinical remission (per Adapted Mayo Score) at week 52. Not all secondary endpoints are shown. All primary and secondary endpoints achieved p-values of <0.001 versus the placebo group. a Clinical remission (per Adapted Mayo Score) is defined as stool frequency subscore (SFS) ≤1 and not greater than baseline, rectal bleeding subscore (RBS) of 0 and endoscopic subscore ≤1. b Endoscopic improvement is defined as endoscopic subscore ≤1. c HEMI is defined as an endoscopic subscore of ≤1 and Geboes score ≤3.1. d Corticosteroid-free remission is defined as clinical remission at week 52 and corticosteroid free for ≥90 days prior to week 52among patients with clinical remission after 8 weeks of induction treatment. N=47, 58 and 54 for the upadacitinib 15 mg,upadacitinib 30 mg and placebo groups, respectively. |
“Ulcerative colitis is a challenging disease to manage, and many patients do not find relief from their most burdensome symptoms,” said Remo Panaccione, M.D., professor of medicine and director of the IBD unit, University of Calgary. “These positive results demonstrate upadacitinib’s potential to achieve improvements in clinical, endoscopic and histological outcomes at 52 weeks. This is promising news for the IBD community.”
A total of 746 patients who completed the 8-week upadacitinib induction treatment with clinical response and received at least one dose of the study drug in the maintenance period were included in the safety analysis.1 The safety results of upadacitinib (15 mg or 30 mg) were consistent with the safety profile observed in the Phase 3 induction studies in ulcerative colitis, as well as in previous studies across indications.1-6 No new safety risks were identified.1-6 The most common adverse events observed in the upadacitinib groups during the 52-week study period were nasopharyngitis, exacerbation of ulcerative colitis and blood creatine phosphokinase increase.1 The exposure-adjusted event rates of serious adverse events per 100 patient years were 12.6 events in the upadacitinib 15 mg group, 10.6 events in the upadacitinib 30 mg group and 21.9 events in the placebo group.1 The rates of serious infections were 4.9, 3.0 and 6.2 events per 100 patient years in the upadacitinib 15 mg, upadacitinib 30 mg and placebo groups, respectively.1 The rates of adverse events leading to treatment discontinuation per 100 patient years were 6.0 events and 6.0 events in patients receiving upadacitinib 15 mg and upadacitinib 30 mg, respectively, compared with 20.3 events in the placebo group.1
Malignancies (excluding non-melanoma skin cancer) reported in the study included one event in the upadacitinib 15 mg group, two events in the upadacitinib 30 mg group and one event in the placebo group.1 Adjudicated thrombotic events were reported in the upadacitinib 15 mg group (two events of pulmonary embolism), 30 mg group (two events of deep vein thrombosis) and the placebo group (one event of ovarian vein thrombosis).1 One adjudicated major adverse cardiovascular event (MACE) was reported in the upadacitinib 30 mg group and one was reported in the placebo group.1 One patient in the placebo group experienced events of adjudicated gastrointestinal perforation.1 No deaths were reported.1
Full results from the Phase 3 maintenance study will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal. Top-line results from the Phase 3 induction studies, U-ACHIEVE and U-ACCOMPLISH, were announced in December 2020 and February 2021, respectively. Use of upadacitinib in ulcerative colitis is not approved and its safety and efficacy have not been evaluated by regulatory authorities.
