Patients treated with upadacitinib for ulcerative colitis experienced better endoscopic and histologic outcomes as well as better mucosal healing compared with patients who received placebo, according to data presented the Congress of the European Crohn’s and Colitis Organisation.
William J. Sandborn, MD, director of the inflammatory bowel disease center at University of California, San Diego Health, said researchers previously studied the efficacy and safety of the drug in the U-ACHIEVE study.
“At the top level, all the primary and secondary endpoints met statistical significance with doses that were equal to or exceeding 30 mg administered once daily,” he said during his presentation. “The rates of adverse events were about what you would expect in a Janus kinase therapy setting.”
Researchers tested histological and endoscopic outcomes of upadacitinib (ABT-494, AbbVie) — an oral, selective Janus kinase-1 inhibitor — in a phase 2 induction study of patients with moderately to severely active UC (adapted Mayo score, 5-9 points; endoscopy subscore, 2-3) who had inadequate response, loss of response or intolerance to corticosteroids, immunosuppressors or biologic therapies.
Investigators randomly assigned patients to 7.5 mg, 15 mg, 30 mg, 45 mg of upadacitinib once daily or placebo for 8 weeks. They stratified patient randomization by previous biologic use, baseline corticosteroid use and baseline adapted Mayo score. They made pairwise comparisons between the upadacitinib doses and placebo for endoscopic improvement, endoscopic remission, histological improvement, histological remission and mucosal healing.
At week 8, Sandborn and colleagues observed a dose-dependent relationship for all efficacy endpoints. The proportions of patients who met the efficacy endpoints were higher in the 30-mg and 45-mg upadacitinib groups compared with the placebo group (P < .05).
“Induction treatment with upadacitinib at the 30 and 45 mg, once-daily doses consistently demonstrated a significant statistical improvement in endoscopic and histologic outcomes compared to placebo,” Sandborn said. – by Alex Young
Sandborn WJ, et al. Abstract OP14. Presented at: Congress of the European Crohn’s and Colitis Organisation; March 7-9, 2019; Copenhagen, Denmark.
Disclosure s : Sandborn reports he receives consultant fees from AbbVie, Akros, Allergan, Ambrx, Amge, Ardelyx, Arena, Atlantic, Avaxia, Boehringer Ingelheim, Bristol-Meyers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBS, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron Ritter Pharmaceuticals, University of Western Ontario, Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB, Pharma, Vascular Biogenics and Vivelix. He reports receiving research grants from AbbVie, Atlantic Healthcare Ltd., Amgen, Celgene/Receptos, Genentech, Gilead Sciences, Janssen, Lilly and Takeda. He also reports receiving payments for lectures/speakers bureau from AbbVie, Janssen and Takeda. He also holds stock/stock options in Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity and Ritter Pharmaceuticals. Please see the ECCO disclosure database for all other authors’ relevant financial disclosures.