A Study to Evaluate the Safety and Efficacy of Upadacitinib (ABT-494) for Induction and Maintenance Therapy in Participants With Moderately to Severely Active Ulcerative Colitis (UC)
Summary
This study was comprised of three substudies. The objective of Substudy 1 was to characterize the dose-response, efficacy, and safety of upadacitinib compared to placebo in inducing clinical remission to identify the induction dose of upadacitinib for further evaluation in Substudy 2. The objective of Substudy 2 was to evaluate the efficacy and safety of upadacitinib compared to placebo in inducing clinical remission in participants. The objective of Substudy 3 was to evaluate the efficacy and safety of upadacitinib compared to placebo in achieving clinical remission in participants who had a response following induction with upadacitinib.
Timeline
- Start
- 2016-09-26
- Primary completion
- 2021-12-13
- Completion
- 2021-12-13
Outcome
Met primary endpoint
registry analysis (superiority test); SS1: Placebo vs SS1: Upadacitinib 15 mg; p = 0.010; Adjusted risk difference (%) 13.5 (95% CI 3.3 to 23.8); NCT02819635 ↗
registry analysis (superiority test); SS2: Placebo vs SS2: Upadacitinib 45 mg; p <0.001; Adjusted risk difference (%) 21.6 (95% CI 15.8 to 27.4); NCT02819635 ↗
registry analysis (superiority test); SS3: Placebo vs SS3: UPA 15 mg; p <0.001; Adjusted risk difference (%) 30.7 (95% CI 21.7 to 39.8); NCT02819635 ↗
release “Results from the U-ACHIEVE study demonstrated that after 8 weeks, upadacitinib (15/30/45 mg, once daily) met the primary endpoint of clinical remission” abbvie.com ↗
release “positive results from the Phase 3 induction study, U-ACHIEVE, which showed upadacitinib (45 mg, once daily) met the primary endpoint” abbvie.com ↗
release “U-ACHIEVE, which showed Rinvoq (45 mg, once daily) met the primary endpoint of clinical remission (per Adapted Mayo Score) at week 8” abbvie.com ↗
Publications
- Burmester GR, Deodhar A, Irvine AD, Panaccione R, Winthrop KL, Vleugels RA, Levy G, Suravaram S, Palac H, Wegrzyn L, Ford S, Meerwein S, Guttman-Yassky E. Safety Profile of Upadacitinib: Descriptive Analysis in Over 27,000 Patient-Years Across Rheumatoid Arthritis, Psoriatic Arthritis, Axial Spondyloarthritis, Atopic Dermatitis, and Inflammatory Bowel Disease. Adv Ther. 2025 Oct;42(10):5215-5237. doi: 10.1007/s12325-025-03328-y. Epub 2025 Aug 28.
- Panes J, Dubinsky MC, Ishiguro Y, Shukla N, Dubcenco E, Remple V, Sharma D, Panaccione R. Achievement of long-term treatment goals in upadacitinib-treated patients with moderately to severely active ulcerative colitis: a post hoc analysis of phase 3 trial data. J Crohns Colitis. 2025 Jul 3;19(7):jjaf095. doi: 10.1093/ecco-jcc/jjaf095.
- Panaccione R, Danese S, Zhou W, Klaff J, Ilo D, Yao X, Levy G, Higgins PDR, Loftus EV Jr, Chen S, Gonzalez YS, Leonard C, Hebuterne X, Lindsay JO, Cao Q, Nakase H, Colombel JF, Vermeire S. Efficacy and safety of upadacitinib for 16-week extended induction and 52-week maintenance therapy in patients with moderately to severely active ulcerative colitis. Aliment Pharmacol Ther. 2024 Feb;59(3):393-408. doi: 10.1111/apt.17816. Epub 2023 Nov 27.
- Raine T, Ishiguro Y, Rubin DT, Finney-Hayward T, Vladea R, Liu J, Phillips C, Cheng E, Targownik L, Loftus EV Jr. Impact of Baseline Corticosteroid Use on the Efficacy and Safety of Upadacitinib in Patients with Ulcerative Colitis: A Post Hoc Analysis of the Phase 3 Clinical Trial Programme. J Crohns Colitis. 2024 May 31;18(5):695-707. doi: 10.1093/ecco-jcc/jjad190.
- Vermeire S, Danese S, Zhou W, Ilo D, Klaff J, Levy G, Yao X, Chen S, Sanchez Gonzalez Y, Hebuterne X, Lindsay JO, Higgins PDR, Cao Q, Nakase H, Colombel JF, Loftus EV Jr, Panaccione R. Efficacy and safety of upadacitinib maintenance therapy for moderately to severely active ulcerative colitis in patients responding to 8 week induction therapy (U-ACHIEVE Maintenance): overall results from the randomised, placebo-controlled, double-blind, phase 3 maintenance study. Lancet Gastroenterol Hepatol. 2023 Nov;8(11):976-989. doi: 10.1016/S2468-1253(23)00208-X. Epub 2023 Sep 9.
- Parkes G, Ungaro RC, Danese S, Abreu MT, Arenson E, Zhou W, Ilo D, Laroux FS, Deng H, Sanchez Gonzalez Y, Peyrin-Biroulet L. Correlation of mucosal healing endpoints with long-term clinical and patient-reported outcomes in ulcerative colitis. J Gastroenterol. 2023 Oct;58(10):990-1002. doi: 10.1007/s00535-023-02013-7. Epub 2023 Jul 25.
- Loftus EV Jr, Ananthakrishnan AN, Lee WJ, Gonzalez YS, Fitzgerald KA, Wallace K, Zhou W, Litcher-Kelly L, Ollis SB, Su S, Danese S. Content Validity and Psychometric Evaluation of the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) in Patients with Crohn's Disease and Ulcerative Colitis. Pharmacoecon Open. 2023 Sep;7(5):823-840. doi: 10.1007/s41669-023-00419-w. Epub 2023 Jun 9.
- Danese S, Tran J, D'Haens G, Rubin DT, Aoyama N, Zhou W, Ilo D, Yao X, Sanchez Gonzalez Y, Panaccione R. Upadacitinib Induction and Maintenance Therapy Improves Abdominal Pain, Bowel Urgency, and Fatigue in Patients With Ulcerative Colitis: A Post Hoc Analysis of Phase 3 Data. Inflamm Bowel Dis. 2023 Nov 2;29(11):1723-1729. doi: 10.1093/ibd/izad016.
- Panes J, Loftus EV, Higgins PDR, Lindsay JO, Zhou W, Yao X, Ilo D, Phillips C, Tran J, Sanchez Gonzalez Y, Vermeire S. Induction and Maintenance Treatment With Upadacitinib Improves Health-Related Quality of Life in Patients With Moderately to Severely Active Ulcerative Colitis: Phase 3 Study Results. Inflamm Bowel Dis. 2023 Sep 1;29(9):1421-1430. doi: 10.1093/ibd/izac260.
- Ponce-Bobadilla AV, Stodtmann S, Eckert D, Zhou W, Liu W, Mohamed MF. Upadacitinib Population Pharmacokinetics and Exposure-Response Relationships in Ulcerative Colitis Patients. Clin Pharmacokinet. 2023 Jan;62(1):101-112. doi: 10.1007/s40262-022-01191-6. Epub 2022 Dec 26.
- Loftus EV Jr, Colombel JF, Takeuchi K, Gao X, Panaccione R, Danese S, Dubinsky M, Schreiber S, Ilo D, Finney-Hayward T, Zhou W, Phillips C, Gonzalez YS, Shu L, Yao X, Zhou Q, Vermeire S. Upadacitinib Therapy Reduces Ulcerative Colitis Symptoms as Early as Day 1 of Induction Treatment. Clin Gastroenterol Hepatol. 2023 Aug;21(9):2347-2358.e6. doi: 10.1016/j.cgh.2022.11.029. Epub 2022 Dec 1.
- Danese S, Vermeire S, Zhou W, Pangan AL, Siffledeen J, Greenbloom S, Hebuterne X, D'Haens G, Nakase H, Panes J, Higgins PDR, Juillerat P, Lindsay JO, Loftus EV Jr, Sandborn WJ, Reinisch W, Chen MH, Sanchez Gonzalez Y, Huang B, Xie W, Liu J, Weinreich MA, Panaccione R. 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 Jun 4;399(10341):2113-2128. doi: 10.1016/S0140-6736(22)00581-5. Epub 2022 May 26.
- Sandborn WJ, Ghosh S, Panes J, Schreiber S, D'Haens G, Tanida S, Siffledeen J, Enejosa J, Zhou W, Othman AA, Huang B, Higgins PDR. Efficacy of Upadacitinib in a Randomized Trial of Patients With Active Ulcerative Colitis. Gastroenterology. 2020 Jun;158(8):2139-2149.e14. doi: 10.1053/j.gastro.2020.02.030. Epub 2020 Feb 22.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Upadacitinib | Small molecule | 7.5 mg | Oral |
| Subject | Upadacitinib | Small molecule | 15 mg | Oral |
| Subject | Upadacitinib | Small molecule | 30 mg | Oral |
| Subject | Upadacitinib | Small molecule | 45 mg | Oral |