[en] BACKGROUND & AIMS: The long-term efficacy and safety of upadacitinib was evaluated in an open-label extension (OLE) of a phase II, double-blind, randomized trial of patients with Crohn's disease. METHODS: Patients who completed the 52-week study (CELEST) received upadacitinib in the CELEST OLE as follows: those who had received immediate-release upadacitinib 3, 6, or 12 mg twice daily or 24 mg once daily (QD) received extended-release upadacitinib 15 mg QD and those who had received immediate-release upadacitinib 12 or 24 mg twice daily as rescue therapy received extended-release upadacitinib 30 mg QD. If any patient initiating upadacitinib 15 mg QD in CELEST OLE lost response at or after week 4, the dose was escalated to upadacitinib 30 mg QD (dose-escalated group). Clinical, endoscopic, inflammatory and quality-of-life measures were assessed. RESULTS: A total of 107 CELEST study completers entered CELEST OLE. The proportion of patients with clinical remission 2.8/1.0 was maintained between week 0 and month 30 in all groups (month 30: 15 mg, 61%; 30 mg, 54%; dose-escalation, 55%). Endoscopic response was maintained in all groups (month 24: 68%, 67%, and 40%, respectively). The rates of adverse events (AEs), serious AEs, AEs leading to discontinuation, infections, serious infections, herpes zoster, and creatine phosphokinase elevation were higher with upadacitinib 30 mg vs 15 mg. CONCLUSION: Sustained long-term benefit at 30 months and further endoscopic improvements to month 24 were observed in patients with Crohn's disease receiving upadacitinib. Safety over 30 months was consistent with the known safety profile of upadacitinib. CLINICALTRIALS: gov ID no: NCT02782663.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
D'Haens, Geert; Department of Gastroenterology and Hepatology, Amsterdam University Medical
Gomollon, F., Dignass, A., Annese, V., et al. ECCO. 3rd European evidence-based consensus on the diagnosis and management of Crohn's disease 2016. Part 1: diagnosis and medical management. J Crohns Colitis 11 (2017), 3–25.
Lichtenstein, G.R., Loftus, E.V., Isaacs, K.L., et al. ACG clinical guideline: management of Crohn's disease in adults. Am J Gastroenterol 113 (2018), 481–517.
Shah, S.C., Colombel, J.F., Sands, B.E., et al. Systematic review with meta-analysis: mucosal healing is associated with improved long-term outcomes in Crohn's disease. Aliment Pharmacol Ther 43 (2016), 317–333.
Rogler, G., Efficacy of JAK inhibitors in Crohn's disease. J Crohns Colitis 14 (2020), S746–S754.
Parmentier, J.M., Voss, J., Graff, C., et al. In vitro and in vivo characterization of the JAK1 selectivity of upadacitinib (ABT-494). BMC Rheumatol, 2, 2018, 23.
De Vries, L.C.S., Wildenberg, M.E., De Jonge, W.J., et al. The future of Janus kinase inhibitors in inflammatory bowel disease. J Crohns Colitis 11 (2017), 885–893.
Sandborn, W.J., Feagan, B.G., Loftus, E.V. Jr., et al. Efficacy and safety of upadacitinib in a randomized trial of patients with Crohn's disease. Gastroenterology 158 (2020), 2123–2138.
Mease, P.J., Lertratanakul, A., Anderson, J.K., et al. Upadacitinib for psoriatic arthritis refractory to biologics: SELECT-PsA 2. Ann Rheum Dis 80 (2020), 312–320.
Cohen, S.B., van Vollenhoven, R.F., Winthrop, K.L., et al. Safety profile of upadacitinib in rheumatoid arthritis: integrated analysis from the SELECT phase III clinical programme. Ann Rheum Dis 80 (2020), 304–311.
Vermeire, S., Schreiber, S., Petryka, R., et al. Clinical remission in patients with moderate-to-severe Crohn's disease treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-controlled trial. Lancet 389 (2017), 266–275.
Panes, J., D'Haens, G.R., Higgins, P.D.R., et al. Long-term safety and tolerability of oral tofacitinib in patients with Crohn's disease: results from a phase 2, open-label, 48-week extension study. Aliment Pharmacol Ther 49 (2019), 265–276.
Panes, J., Sandborn, W.J., Schreiber, S., et al. Tofacitinib for induction and maintenance therapy of Crohn's disease: results of two phase IIb randomised placebo-controlled trials. Gut 66 (2017), 1049–1059.
Winthrop, K.L., Yamanaka, H., Valdez, H., et al. Herpes zoster and tofacitinib therapy in patients with rheumatoid arthritis. Arthritis Rheumatol 66 (2014), 2675–2684.
Genovese, M.C., Fleischmann, R., Combe, B., et al. Safety and efficacy of upadacitinib in patients with active rheumatoid arthritis refractory to biologic disease-modifying anti-rheumatic drugs (SELECT-BEYOND): a double-blind, randomised controlled phase 3 trial. Lancet 391 (2018), 2513–2524.
Smolen, J.S., Pangan, A.L., Emery, P., et al. Upadacitinib as monotherapy in patients with active rheumatoid arthritis and inadequate response to methotrexate (SELECT-MONOTHERAPY): a randomised, placebo-controlled, double-blind phase 3 study. Lancet 393 (2019), 2303–2311.
Grainge, M.J., West, J., Card, T.R., Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study. Lancet 375 (2010), 657–663.
Filimon, A.M., Negreanu, L., Doca, M., et al. Cardiovascular involvement in inflammatory bowel disease: dangerous liaisons. World J Gastroenterol 21 (2015), 9688–9692.
Aniwan, S., Pardi, D.S., Tremaine, W.J., et al. Increased risk of acute myocardial infarction and heart failure in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 16 (2018), 1607–1615.e1.
