Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel—EPACT II
Received 14 March 2009; accepted 28 March 2009. published online 18 May 2009.
Abstract
Introduction
High-grade evidence is lacking for most therapeutic decisions in Crohn's disease. Appropriateness criteria were developed for upper gastro-intestinal, extra-intestinal manifestations and drug safety during conception, pregnancy and breastfeeding in patients with Crohn's disease, to assist the physician in clinical decision making.
Methods
The European Panel on the Appropriateness of Crohn's Disease Therapy (EPACT II), a multidisciplinary international European expert panel, rated clinical scenarios based on evidence from the published literature and panelists' own clinical expertise. Median ratings (on a 9-point scale) were stratified into three categories: appropriate (7–9), uncertain (4–6 with or without disagreement) and inappropriate (1–3). Experts were also asked to rank appropriate medications by priority.
Results
Proton pump inhibitors, steroids, azathioprine/6-mercaptopurine and infliximab are appropriate for upper gastro-duodenal Crohn's disease; for stenosis, endoscopic balloon dilation is the first-line therapy, although surgery is also appropriate. Ursodeoxycholic acid is the only appropriate treatment for primary sclerosing cholangitis. Infliximab is appropriate for Pyoderma gangrenosum, ankylosing spondylitis and uveitis, steroids for Pyoderma gangrenosum and ankylosing spondylitis, adalimumab for Pyoderma gangrenosum and ankylosing spondylitis, cyclosporine-A/tacrolimus for Pyoderma gangrenosum. Mesalamine, sulfasalazine, prednisone, azathioprine/6-mercaptopurine, ciprofloxacin, and probiotics, may be administered safely during pregnancy or for patients wishing to conceive, with the exception that male patients considering conception should avoid sulfasalazine. Metronidazol is considered safe in the 2nd and 3rd trimesters whereas infliximab is rated safe in the 1st trimester but uncertain in the 2nd and 3rd trimesters. Methotrexate is always contraindicated at conception, during pregnancy or during breastfeeding, due to its known teratogenicity. Mesalamine, prednisone, probiotics and infliximab are considered safe during breastfeeding.
Conclusion
EPACT II recommendations are freely available online (www.epact.ch). The validity of these criteria should now be tested by prospective evaluation.
aDepartment of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
bHealthcare Evaluation Unit, Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland
cDepartment of Gastroenterology, University of Basle, Basle, Switzerland
dDepartment of Internal Medicine and Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands
eDipartimento di Scienze Cliniche, Università di Roma “La Sapienza”, Rome, Italy
fDepartment of Gastroenterology, Inselspital, Bern, Switzerland
Corresponding author. Department of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois Rue du Bugnon 46, CH-1011 Lausanne, Switzerland. Tel.: +41 21 314 0690; fax: +41 21 314 0707.
1 The EPACT II Study Group (in alphabetical order): Erika Angelucci (Italy), Willem Bemelman (The Netherlands), Miquel Gassull (Spain), Franz Josef Heil (Germany), Marc Lémann (France), Tom Öresland (Norway), Colm O'Morain (Ireland), Yves Panis (France), Frank Seibold (Switzerland), Eduard Stange (Germany), Reinhold Stockbrügger (The Netherlands) and Boris Vucelic (Croatia).
ABSTRACT