PMID- 25281416 OWN - NLM STAT- MEDLINE DCOM- 20150923 LR - 20211021 IS - 1468-3288 (Electronic) IS - 0017-5749 (Print) IS - 0017-5749 (Linking) VI - 64 IP - 8 DP - 2015 Aug TI - A phase II study of laquinimod in Crohn's disease. PG - 1227-35 LID - 10.1136/gutjnl-2014-307118 [doi] AB - 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. CI - Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. FAU - D'Haens, Geert AU - D'Haens G AD - Academic Medical Center, Amsterdam, The Netherlands. FAU - Sandborn, William J AU - Sandborn WJ AD - Academic Medical Center, Amsterdam, The Netherlands University of California San Diego, La Jolla, USA Icahn School of Medicine at Mount Sinai, New York, New York, UK Catholic University of Leuven, Belgium Teva Pharmaceuticals, Frazer, Pennsylvania, USA Teva Pharmaceuticals, Netanya, Israel Formerly Teva Pharmaceuticals, Netanya, Israel Chiasma Pharma, Jerusalem, Israel Robarts Research Institute University of Western Ontario, London, Ontario, Canada. FAU - Colombel, Jean Frederic AU - Colombel JF AD - University of California San Diego, La Jolla, USA Icahn School of Medicine at Mount Sinai, New York, New York, UK. FAU - Rutgeerts, Paul AU - Rutgeerts P AD - Catholic University of Leuven, Belgium. FAU - Brown, Kurt AU - Brown K AD - Teva Pharmaceuticals, Frazer, Pennsylvania, USA. FAU - Barkay, Hadas AU - Barkay H AD - Teva Pharmaceuticals, Netanya, Israel. FAU - Sakov, Anat AU - Sakov A AD - Teva Pharmaceuticals, Netanya, Israel. FAU - Haviv, Asi AU - Haviv A AD - Formerly Teva Pharmaceuticals, Netanya, Israel Chiasma Pharma, Jerusalem, Israel. FAU - Feagan, Brian G AU - Feagan BG AD - Robarts Research Institute University of Western Ontario, London, Ontario, Canada. CN - Laquinimod for Crohn's Disease Investigators LA - eng SI - ClinicalTrials.gov/NCT00737932 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20141003 PL - England TA - Gut JT - Gut JID - 2985108R RN - 0 (Anti-Inflammatory Agents) RN - 0 (Quinolones) RN - 908SY76S4G (laquinimod) SB - IM MH - Administration, Oral MH - Adolescent MH - Adult MH - Aged MH - Anti-Inflammatory Agents/administration & dosage MH - Crohn Disease/*drug therapy MH - Dose-Response Relationship, Drug MH - Double-Blind Method MH - Female MH - Follow-Up Studies MH - Humans MH - Induction Chemotherapy/*methods MH - Male MH - Middle Aged MH - Quinolones/*administration & dosage MH - Treatment Outcome MH - Young Adult PMC - PMC4515993 OTO - NOTNLM OT - CLINICAL DECISION MAKING OT - CLINICAL TRIALS OT - CROHN'S DISEASE OT - IBD CLINICAL OT - PHARMACOTHERAPY FIR - D'Haens, Geert IR - D'Haens G FIR - Vermeire, Severine IR - Vermeire S FIR - Baert, Filip IR - Baert F FIR - Colombel, Jean Frederic IR - Colombel JF FIR - Dupas, Jean-Louis IR - Dupas JL FIR - Bouhnik, Yoram IR - Bouhnik Y FIR - Bonaz, Bruno IR - Bonaz B FIR - Hebuterne, Xavier IR - Hebuterne X FIR - Allez, Matthieu IR - Allez M FIR - Israeli, Eran IR - Israeli E FIR - Fraser, Gerald IR - Fraser G FIR - Segol, Ori IR - Segol O FIR - Fishman, Sigal IR - Fishman S FIR - Lahat, Adi IR - Lahat A FIR - Melzer, Ehud IR - Melzer E FIR - Pallone, Francesco IR - Pallone F FIR - Campieri, Massimo IR - Campieri M FIR - Gasbarrini, Antonio IR - Gasbarrini A FIR - Kohn, Anna IR - Kohn A FIR - Vecchi, Maurizo IR - Vecchi M FIR - Ponsioen, Cyriel IR - Ponsioen C FIR - Van der Woude, Janneke IR - Van der Woude J FIR - Rydzewska, Grazyna IR - Rydzewska G FIR - Mach, Tomasz IR - Mach T FIR - Paradowski, Leszek IR - Paradowski L FIR - Wright, John Philip IR - Wright JP FIR - Watermeyer, Gillian Ann IR - Watermeyer GA FIR - Pettengell, Keith Edward IR - Pettengell KE FIR - Mahomed, Adam Dawood IR - Mahomed AD FIR - Prins, Maarten Jeroen IR - Prins MJ FIR - Aboo, Nazimuddin IR - Aboo N FIR - Diaz, Julian Panes IR - Diaz JP FIR - Taxonera, Carlos IR - Taxonera C FIR - Gisbert, Javier IR - Gisbert J FIR - Hinojosa, Joaquin IR - Hinojosa J FIR - Garcia, Fernand Gomollon IR - Garcia FG FIR - Sanchez, Valle Garcia IR - Sanchez VG FIR - Parkes, Miles IR - Parkes M FIR - Probert, Chris IR - Probert C FIR - Leiper, Keith IR - Leiper K FIR - Nwokolo, Chuka IR - Nwokolo C FIR - Mayberry, John IR - Mayberry J FIR - Bloom, Stuart IR - Bloom S EDAT- 2014/10/05 06:00 MHDA- 2015/09/24 06:00 PMCR- 2015/07/27 CRDT- 2014/10/05 06:00 PHST- 2014/02/25 00:00 [received] PHST- 2014/07/31 00:00 [accepted] PHST- 2014/10/05 06:00 [entrez] PHST- 2014/10/05 06:00 [pubmed] PHST- 2015/09/24 06:00 [medline] PHST- 2015/07/27 00:00 [pmc-release] AID - gutjnl-2014-307118 [pii] AID - 10.1136/gutjnl-2014-307118 [doi] PST - ppublish SO - Gut. 2015 Aug;64(8):1227-35. doi: 10.1136/gutjnl-2014-307118. Epub 2014 Oct 3.