nature publishing group CLINICAL AND SYSTEMATIC REVIEWS REVIEW 199 © 2011 by the American College of Gastroenterology The American Journal of GASTROENTEROLOGY The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn’ s and Colitis Organization: When to Start, When to Stop, Which Drug to Choose, and How to Predict Response? Geert R. D’Haens, MD, PhD 1 , Remo Panaccione, MD 2 , Peter D.R. Higgins, MD 3 , Severine Vermeire, MD, PhD 4 , Miquel Gassull, MD, PhD 5 , Yehuda Chowers, MD 6 , Stephen B. Hanauer, MD 7 , Hans Herfarth, MD 8 , Daan W. Hommes, MD, PhD 9 , Michael Kamm, MD 10,11 , Robert Löfberg, MD 12 , A. Quary 13 , Bruce Sands, MD 14 , A. Sood, MD 15 , G. Watermayer 16 , Bret Lashner, MD 17 , Marc Lémann, MD 18 , Scott Plevy 19 , Walter Reinisch, MD 20 , Stefan Schreiber, MD, PhD 21 , Corey Siegel, MD 22 , Stephen Targan, MD 23 , M. Watanabe, MD 24 , Brian Feagan, MD 25 , William J. Sandborn, MD 26 , Jean Frédéric Colombel, MD, PhD 27 and Simon Travis, MD 28 The advent of biological therapy has revolutionized inflammatory bowel disease (IBD) care. Nonetheless, not all patients require biological therapy. Selection of patients depends on clinical characteristics, previous response to other medical therapy, and comorbid conditions. Availability, reimbursement guidelines, and patient preferences guide the choice of first-line biological therapy for luminal Crohn’s disease (CD). Infliximab (IFX) has the most extensive clinical trial data, but other biological agents (adalimumab (ADA), certolizumab pegol (CZP), and natalizumab (NAT)) appear to have similar benefits in CD. Steroid-refractory, steroid-dependent, or complex fistulizing CD are indications for starting biological therapy, after surgical drainage of any sepsis. For fistulizing CD, the efficacy of IFX for inducing fistula closure is best documented. Unique risks of NAT account for its labeling as a second-line biological agent in some countries. Patients who respond to induction therapy benefit from systematic re-treatment. The combination of IFX with azathioprine is better than monotherapy for induction of remission and mucosal healing up to 1 year in patients who are naïve to both agents. Whether this applies to other agents remains unknown. IFX is also effective for treatment-refractory, moderate, or severely active ulcerative colitis. Patients who have a diminished or loss of response to anti-tumor necrosis factor (TNF) therapy may respond to dose adjustment of the same agent or switching to another agent. Careful consideration should be given to the reasons for loss of response. There are insufficient data to make recommendations on when to stop anti-TNF therapy. Preliminary evidence suggests that a substantial proportion of patients in clinical remission for > 1 year, without signs of active inflammation can remain in remission after stopping treatment. Am J Gastroenterol 2011; 106:199–212; doi:10.1038/ajg.2010.392; published online 2 November 2010 1 Department of Gastroenterology, Academic Medical Centre, Amsterdam, The Netherlands; 2 Inflammatory Bowel Disease Clinic, University of Calgary , Calgary , Alberta, Canada; 3 Department of Internal Medicine, University of Michigan, Ann Arbor , Michigan, USA; 4 Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 5 Health Sciences Research Institute, Germans Trias i Pujol Foundation, Badalona, Spain; 6 Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel; 7 Section of Gastroenterogy, Hepatology & Nutrition, The University of Chicago Medical Center , Chicago, Illinois, USA; 8 Division of Gastroenterology & Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA; 9 Department of Gastroenterology, Leiden University Medical Centre—LUMC, Leiden, The Netherlands; 10 Department of Medicine, St. Vincent’s Hospital, Melbourne, Victoria, Australia; 11 Imperial College, London, UK; 12 IBD Unit, Sophiahemmet, Stockholm, Sweden; 13 King Abdulaziz University Hospital, Jeddah, Saudi Arabia; 14 MGH Crohn’s and Colitis Center, Massachusetts General Hospital, Boston, Massachusetts, USA; 15 Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India; 16 Division of Gastroenterology and Department of Medicine, Groote Schuur Hospital, Cape Town, South Africa; 17 Department of Gastroenterology, Cleveland Clinic, Cleveland, Ohio, USA; 18 Department of Gastroenterology, Hospital St Louis, Paris, France; 19 UNC School of Medicine, Chapel Hill, North Carolina, USA; 20 Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria; 21 Department of General Internal Medicine, University Hospital Schleswig-Holstein UKSH, Kiel, Germany; 22 Section of Gastroenterology and Hepatology, Dartmouth-Hitchcock Medical Center , Lebanon, New Hampshire, USA; 23 Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, California, USA; 24 Department of Gastroenterology and Hepatology,Tokyo Medical and Dental University , Tokyo, Japan; 25 The University of Western Ontario, London, Ontario, Canada; 26 Mayo Clinic, Rochester , Minnesota, USA; 27 Department of Hepato-Gastroenterology, Hospital Huriez, Lille, France; 28 Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK. Correspondence: Geert R. D’Haens, MD, PhD, Academic Medical Center, Department of Gastroenterology , Amsterdam, The Netherlands. E-mail: g.dhaens@amc.uva.nl Received 1 March 2010; accepted 6 September 2010 see related editorial on page 225