¹Humanitas University Clinical and Research Hospital, Rozzano, Milan, Italy, ²University Hospitals Leuven, Leuven, Belgium, ³Nature Coast Clinical Research, Inverness, Florida, United States, ⁴University of Calgary, Calgary, Canada, ⁵University of Zürich, Zürich, Switzerland, ⁶Rabin Medical Centre and University of Tel-Aviv, Petah Tikva, Israel, ⁷AO San Camillo Forlanini, Rome, Italy, ⁸University of Lille, Inserm U995, Lille, France, ⁹Concord Hospital, Sydney, New South Wales, Australia, ¹⁰Pfizer Inc, Cambridge, Massachusetts, United States, ¹¹Pfizer Inc, Collegeville, Pennsylvania, United States, ¹²Christian-Albrechts University, Kiel, Germany

¹Shaare Zedek Medical Centre, Paediatrics, Jerusalem, Israel, ²The Hebrew University, Jerusalem, Israel, ³Sapienza University of Rome, Rome, Italy, ⁴Yorkhill Children’s Hospital, Glasgow, United Kingdom, ⁵Medical University of Warsaw, Warsaw, Poland, ⁶University Hospital Southampton, Hampshire, United Kingdom, ⁷University of Dundee, Scotland, United Kingdom, ⁸Zagreb University Medical School, Zagreb, Croatia, ⁹University of Messina, Messina, Italy, ¹⁰St Marien Hospital, Bonn, Germany, ¹¹Hvidovre University Hospital, Copenhagen, Denmark, ¹²Erasmus Medical Centre, Holland, Netherlands, ¹³Shaare Zedek Medical Centre, Jerusalem, Israel

¹University of New South Wales, St Vincent’s Clinical School, Sydney, Australia, ²St Vincent’s Hospital, Melbourne, Australia, ³Imperial College London, London, United Kingdom, ⁴St Vincent’s Hospital, Sydney, Australia, ⁵Nambour General Hospital, Nambour, Australia, ⁶Bankstown-Lidcombe Hospital, Sydney, Australia, ⁷Liverpool Hopsital, Sydney, Australia, ⁸University of New South Wales, School of Biotechnology & Biomolecular Sciences, Sydney, Australia, ⁹Ingham Institute, Sydney, Australia, ¹⁰Centre for Digestive Diseases, Sydney, Australia

¹Human Nutrition, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow Royal Infirmary, Glasgow, United Kingdom, ²Department of Paediatric Gastroenterology, Hepatology and Nutrition, Royal Hospital for Children, Glasgow, United Kingdom, ³School of Engineering, University of Glasgow, Glasgow, United Kingdom, ⁴Warwick Medical School, University of Warwick, Warwick, United Kingdom, ⁵Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, United Kingdom

¹Division of Gastroenterology, University of California, San Diego, California, United States, ²Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, United States, ³Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands, ⁴Dept of Gastroenterology, University Hospitals Leuven, Leuven, Belgium, ⁵Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany, ⁶IBD Centre, Department of Gastroenterology, Humanitas Research Hospital, Milan, Italy, ⁷Hospital Clinicas de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, ⁸Robarts Research Institute, London, Ontario, Canada, ⁹McMaster University, Hamilton, Canada, ¹⁰Pfizer Inc, Collegeville, Pennsylvania, United States, ¹¹Pfizer Inc, Groton, Connecticut, United States

¹UZ Leuven, Campus Gasthuisberg, Leuven, Belgium, ²University Medical Centre Schleswig-Holstein Kiel, Department of Internal Medicine I, Kiel, Germany, ³Vivamed, Warsaw, Poland, ⁴Asklepios Hospital West Hamburg, Department of Internal Medicine, Gastroenterology, Hamburg, Germany, ⁵Archet 2 Hospital, Department of Gastroenterology, Nice, France, ⁶Saint Etienne Hospital, Department of Gastroenterology, Saint Priest en Jarez, France, ⁷University Hospital Nr. 2 im. Biziela, Department of Gastroenterology, Bydgoszcz, Poland, ⁸Policlinica Algomed, Department of Gastroenterology, Timisoara, Romania, ⁹Saint Family Hospital Medical Centre, Department of Gastroenterology and Endoscopy, Lodz, Poland, ¹⁰City Clinical Hospital #31, St Petersburg, Russian Federation, ¹¹Szent Margit Hospital, Department of Internal Medicine and Gastroenterology III, Budapest, Hungary, ¹²Galapagos NV, Department of Development, Mechelen, Belgium

Filgotinib is an oral, selective Janus kinase 1 (JAK1) inhibitor, which has demonstrated high efficacy in patients with rheumatoid arthritis. This 20-week Phase 2 study was designed to evaluate the efficacy and safety of filgotinib in patients with active Crohn’s disease.

¹Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands, ²University of Calgary, Calgary, Canada, ³University of Michigan, Ann Arbor, Michigan, United States, ⁴Robarts Research Institute, London, Ontario, Canada, ⁵Pfizer Inc, Collegeville, Pennsylvania, United States, ⁶Pfizer Inc, Groton, Connecticut, United States

¹Hospital Clinicas de Barcelona, IDIBAPS, CIBERehd, Barcelona, Spain, ²Division of Gastroenterology, University of California, San Diego, United States, ³Klinik für Innere Medizin I, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Germany, ⁴Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, United States, ⁵Dept of Gastroenterology, University Hospitals Leuven, Leuven, Belgium, ⁶Pfizer Inc, Collegeville, United States, ⁷Pfizer Inc, Groton, United States

¹Osaka City General Hospital, Gastroenterology, Osaka, Japan, ²Nishishita Gastrointestinal Hospital, Osaka, Japan, ³Faculty of Human Culture and Science Prefectural University of Hiroshima, Hiroshima, Japan, ⁴Osakafu Saiseikai Nakatsu Hospital, Gastroenterology and Hepatology, Osaka, Japan, ⁵Graduate School of Medical Sciences, Kyushu University, Department of Medicine and Clinical Science, Fukuoka, Japan, ⁶Hiroshima University Hospital, Department of Endoscopy, Hiroshima, Japan, ⁷Kyoto Katsura Hospital, Digestive Disease Centre, Department of Gastroenterology, Kyoto, Japan, ⁸Fukuoka University Chikushi Hospital, Department of Gastroenterology, Fukuoka, Japan, ⁹Osaka Medical College, Second Department of Internal Medicine, Osaka, Japan, ¹⁰Hyogo College of Medicine, Department of Inflammatory Bowel Disease, Hyogo, Japan, ¹¹Takano Hospital, Division of Gastroenterology, Coloproctology Centre, Kumamoto, Japan, ¹²Kinki University, Department of Gastroenterology, Osaka, Japan, ¹³Toho University Sakura Medical Centre, Department of Internal Medicin, Chiba, Japan, ¹⁴The Jikei University School of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tokyo, Japan, ¹⁵The Jikei University School of Medicine, Department of Endoscopy, Tokyo, Japan, ¹⁶National Cancer Centre Hospital, Endoscopy Division, Tokyo, Japan, ¹⁷School of Medicine, Fujita Health University, Department of Gastroenterology, Aichi, Japan, ¹⁸Toho University Sakura Medical Centre, Department of Internal Medicine, Chiba, Japan, ¹⁹Graduate School of Medical and Dental Sciences, Niigata University, Division of Molecular and Diagnostic Pathology, Niigata, Japan, ²⁰The Jikei University School of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Department of Endoscopy, Tokyo, Japan

¹UZ Leuven, Gastroenterology, Leuven, Belgium, ²UZ Leuven, Campus Gasthuisberg, Pathology, Leuven, Belgium

¹St Mark’s Hospital, IBD, London, United Kingdom, ²Imperial College London, Department of Surgery and Cancer, London, United Kingdom, ³St Mark’s Hospital, Wolfson Unit For Endoscopy, Department of Gastroenterology, Harrow, United Kingdom

¹NHS Lothian, Gastroenterology, Edinburgh, United Kingdom, ²NHS Tayside, Gastroenterology, Dundee, United Kingdom, ³University of Edinburgh, Edinburgh Clinical Trials Unit, Edinburgh, United Kingdom, ⁴University of Edinburgh, Gastroenterology, Edinburgh, United Kingdom, ⁵NHS Greater Glasgow and Clyde, Gastroenterology, Glasgow, United Kingdom, ⁶University of Edinburgh, Institute of Genetics and Molecular Medicine, Edinburgh, United Kingdom, ⁷University College Hospital, Department of Gastroenterology, London, United Kingdom, ⁸Bart’s Health NHS Trust, Newham University Hospital, Department of Gastroenterology, London, United Kingdom, ⁹Royal Liverpool University Hospital, Gastroenterology, Liverpool, United Kingdom, ¹⁰Toppic Trial Study Group, UK, United Kingdom

¹Bicêtre Hospital - Université Paris Sud, Oncologic and Digestive Surgery, Le Kremlin-Bicêtre, France, ²Beajon Hospital, Colorectal Surgery, Clichy, France, ³CHU Lille, Digestive Surgery, Lille, France, ⁴Saint Antoine Hospital, Digestive Surgery, Paris, France, ⁵CHU Bordeaux, Digestive Surgery, Bordeaux, France, ⁶CHU Nancy, Digestive Surgery, Nancy, France, ⁷CHU Lyon-Sud, Digestive Surgery, Lyon, France, ⁸CHU Marseille, Digestive Surgery, Marseille, France, ⁹Saint Louis Hospital, Digestive Surgery, Paris, France, ¹⁰CHU Rennes, Digestive Surgery, Rennes, France, ¹¹CHU Nice, Digestive Surgery, Nice, France, ¹²CHU Toulouse, Digestive Surgery, Toulouse, France, ¹³Lariboisière Hospital, Digestive Surgery, Paris, France, ¹⁴Montsouris insitute, Digestive Surgery, Paris, France, ¹⁵CHU Rouen, Digestive Surgery, Rouen, France, ¹⁶CHU Nantes, Digestive Surgery, Nantes, France, ¹⁷CHU Grenoble, Digestive Surgery, Grenoble, France, ¹⁸Saint-Joseph Hospital, Digestive Surgery, Paris, France, ¹⁹CHU Montpellier, Digestive Surgery, Montpellier, France, ²⁰Fernand Widal Hospital, Clinical research, Paris, France

¹Janssen R & D, LLC, Spring House, Pennsylvania, United States, ²Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States, ³Robarts Clinical Trials Inc., Robarts Research Institute, University of Western Ontario, London, Ontario, Canada, ⁴UCSD, Medicine, La Jolla, California, United States

¹Academic Medical Centre, Gastroenterology, Amsterdam, Netherlands, ²University Hospitals Gasthuisberg, Gastroenterology, Leuven, Belgium, ³AZ Damiaan, Oostende, Belgium, ⁴AZ Delta, Roeselare, Belgium, ⁵Imelda GI Clinical Research Centre, Bonheiden, Belgium, ⁶Hopital Claude Hurriez, Lille, France, ⁷Hopital Estaing, Clermont-Ferrand, France, ⁸Hopital Beaujon, Clichy, France, ⁹Hospital Archet, Nice, France, ¹⁰Erasmus Medical Centre, Rotterdam, Netherlands, ¹¹St Lukas Hospital, Bruges, Belgium, ¹²Hopital Rangueil, Toulouse, France, ¹³Hopital Sart Tilman, Liège, Belgium, ¹⁴Hopital Erasme, Brussels, Belgium, ¹⁵University of Ghent, Ghent, Belgium, ¹⁶Free University of Brussels, Brussels, Belgium, ¹⁷Hopital Brabois, Nancy, France, ¹⁸Hopital Robert Debre, Reims, France, ¹⁹Hopital St Louis, Paris, France, ²⁰Ziekenhuis Oost Limburg, Genk, Belgium, ²¹Hopital Trousseau, Tours, France, ²²University of Utrecht, Utrecht, Netherlands, ²³University Hospital Maastricht, Maastricht, Netherlands, ²⁴University of Leuven, Leuven, Belgium, ²⁵Dept Biostatistique St Louis, Paris, France, ²⁶Haut-Leveque, Pessac, France

The most potent available treatment for active Crohn’s disease (CD) is a combination of infliximab (IFX) and azathioprine, leading to disappearance of ulcerations in up to 50% of patients. Because superior outcomes have been associated with serum drug concentrations within what is considered a ‘therapeutic window’, we hypothesised that prospective therapeutic drug monitoring (TDM) would lead to higher remission rates as compared with pure symptom-based dose adaptations.

This was a prospective randomised, double-blinded, multicentre controlled trial in which biologic naïve adult patients with active CD (CDAI > 220, serum CRP > 5 mg/L, and/or faecal calprotectin > 250 µg/g and endoscopic ulcerations) received induction treatment with 3 infusions of IFX 5 mg/kg in combination with azathioprine 2–2.,5 mg/kg/day or MTX in case of intolerance. At week 14, patients were randomised to 1 of 3 different maintenance strategies: 1) dose intensification of IFX in (maximally 2) steps of 2,5 mg/kg based on clinical symptoms, biomarker analysis and serum IFX concentrations drawn before the previous infusion (group 1); 2) dose intensification of IFX from 5 to 10 mg/kg based on the same criteria (group 2), and 3) IFX dose increase to 10 mg/kg based on clinical symptoms alone (group 3). The primary endpoint of the trial was sustained steroid-free clinical remission from week 22 to -54 and absence of ulceration at 1 year based on centrally read endoscopies. Target for IFX dosing was a trough concentration > 3 ug/ml. (EUDRACT NUMBER: 2011-003038-14)

At 27 sites in Belgium, France, and the Netherlands,167 patients were screened, and 122 were randomised (71 F, median age 29.8 years). The 3 groups had comparable patient characteristics. The primary endpoint based on local endoscopy reads was attained in 21/45 (47%) in group 1, 14/37 (38%) in group 2, and 16/40 (40%) in group 3 (p = NS). The proportions of patients without ulcerations at week 54 were 36%, 43%, and 48% (p = NS) and with endoscopic remission (CDEIS < 3) 49%, 51%, and 45% (p = NS). Dose intensification was done in 51%, 65%, and 40% of the patients.

In this prospective randomised exploratory trial in patients with active CD, proactive trough-level–based dose intensification was not superior to dose intensification based on symptoms alone. Results with centrally read endoscopy are being awaited, as well as detailed pharmacokinetic, immunogenicity, and biomarker analysis. More benefit from TDM may be obtained during induction and in dose reduction efforts, which was not studied in this trial.

¹Kitasato University Kitasato Institute Hospital, Centre for Advanced IBD Research and Treatment, Tokyo, Japan, ²Toho University Sakura Medical Centre, Department of Internal Medicine, Sakura, Japan, ³Sapporo-kosei General Hospital, Inflammatory Bowel Diseases Centre, Sapporo, Japan, ⁴Fukuoka University Chikushi Hospital, Department of Gastroenterology, Chikushino, Japan, ⁵Keio University School of Medicine, Centre for Diagnostic and Therapeutic Endoscopy, Tokyo, Japan, ⁶Kitano Hospital The Tazuke Kofukai Medical Research Institute, Digestive Disease Centre, Osaka, Japan, ⁷Mitsubishi Tanabe Pharma Corporation, Osaka, Japan, ⁸Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Tokyo, Japan

University of Erlangen-Nuremberg, Department of Medicine I, Erlangen, Germany

University of Parma, Department of Pharmacy, Parma, Italy

¹University of Campinas, Coloproctology Unit, Surgery Department, Campinas, Brazil, ²University of Campinas, Campinas, Brazil, ³University of Campinas, Laboratory of Cell Signalling, Internal Medicine Department, Campinas, Brazil

¹KU Leuven, Department of Human Genetics, Leuven, Belgium, ²KU Leuven, Department of Clinical and Experimental Medicine, Translational Research Centre for Gastrointestinal Disorders, Leuven, Belgium, ³KU Leuven, Department of Cellular and Molecular Medicine, Gene Expression Unit, Leuven, Belgium