A phase II study of laquinimod in Crohn's disease. Issue 8 (3rd October 2014)

• Record Type: Journal Article
• Authors: D'Haens, Geert; Sandborn, William J; Colombel, Jean Frederic; Rutgeerts, Paul; Brown, Kurt; Barkay, Hadas; Sakov, Anat; Haviv, Asi; Feagan, Brian G
• Other Names: author non-byline.; Baert Filip author non-byline.; Dupas Jean-Louis author non-byline.; Bouhnik Yoram author non-byline.; Bonaz Bruno author non-byline.; Hebuterne Xavier author non-byline.; Allez Matthieu author non-byline.; Israeli Eran author non-byline.; Fraser Gerald author non-byline.; Segol Ori author non-byline.; Fishman Sigal author non-byline.; Lahat Adi author non-byline.; Melzer Ehud author non-byline.; Pallone Francesco author non-byline.; Campieri Massimo author non-byline.; Gasbarrini Antonio author non-byline.; Kohn Anna author non-byline.; Vecchi Maurizo author non-byline.; Ponsioen Cyriel author non-byline.; Van der Woude Janneke author non-byline.; Rydzewska Grazyna author non-byline.; Mach Tomasz author non-byline.; Paradowski Leszek author non-byline.; Wright John Philip author non-byline.; Watermeyer Gillian Ann author non-byline.; Pettengell Keith Edward author non-byline.; Mahomed Adam Dawood author non-byline.; Prins Maarten Jeroen author non-byline.; Aboo Nazimuddin author non-byline.; Diaz Julian Panes author non-byline.; Taxonera Carlos author non-byline.; Gisbert Javier author non-byline.; Hinojosa Joaquin author non-byline.; Garcia Fernand Gomollon author non-byline.; Sanchez Valle Garcia author non-byline.; Parkes Miles author non-byline.; Probert Chris author non-byline.; Leiper Keith author non-byline.; Nwokolo Chuka author non-byline.; Mayberry John author non-byline.; Bloom Stuart author non-byline.;
• Is Part Of: Gut. Volume 64:Issue 8(2015)
• Page Start: 1227
• Page End: 1235
• Publication Date: 2014-10-03
• Subjects: CROHN'S DISEASE -- PHARMACOTHERAPY -- IBD CLINICAL -- CLINICAL TRIALS -- CLINICAL DECISION MAKING; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2014-307118
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Objective: Laquinimod is an oral therapeutic agent under investigation for the treatment of Crohn's disease (CD), Huntington's disease, lupus nephritis and multiple sclerosis. This dose escalation study evaluated the safety and efficacy of laquinimod as induction therapy in patients with active moderate–severe CD. Design: Multicentre, double-blind, sequential-cohort, randomised controlled trial with laquinimod doses of 0.5, 1, 1.5 or 2 mg/day or placebo (n=45 per cohort randomised in a 2:1 ratio) for 8 weeks with 4-week follow-up. Stable concomittant therapies and prior use of anti-tumour necrosis factor agents were permitted. Comprehensive safety assessments were performed and efficacy analyses included the proportions of patients in clinical remission (CD Activity Index (CDAI) <150 and no treatment failure (TF)), and with a clinical response (70 or 100 point CDAI reduction from baseline or remission and no TF). Results: 117 patients received laquinimod and 63 patients received placebo. The overall incidence of adverse events (AEs) in the laquinimod group was similar to the pooled placebo group (86.2%–96.7% vs 82.5%) and most AEs were mild to moderate in severity. Treatment with laquinimod 0.5 mg showed consistent effects on remission (48.3% (CI 31% to 66%) vs 15.9% (CI 9% to 27%)), response 100 (55.2% (CI 37% to 71%) vs 31.7% (CI 22% to 44%)) and response 70 (62.1% (CI 44% to 77%) vs 34.9% (CI 24% to 47%)) versus placebo. Laquinimod 1.0 mg showed less benefit (26.7% remission (CI 14% to 44%) and 53.3% response 70 (CI 36% to 70%)), and no effect was noted on remission/response at higher doses. Conclusions: Laquinimod was safe and well tolerated, and the effects on remission and response of the 0.5 mg dose suggest a treatment benefit in patients with CD. Trial registration number: NCT00737932.