1. Early Administration of Azathioprine Versus Conventional Management of Crohn’s Disease : A Randomized Controlled Trial F1. Ja Won Koo JACQUES COSNES, ANNE BOURRIER, DAVID LAHARIE, STÉPHANE NAHON, YORAM BOUHNIK, FRANCK CARBONNEL, MATTHIEU ALLEZ, JEAN–LOUIS DUPAS, JEAN–MARIE REIMUND, GUILLAUME SAVOYE, PAULINE JOUET, JACQUES MOREAU, JEAN–YVES MARY, and JEAN–FRÉDÉRIC COLOMBEL, for the Groupe d’Etude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) Gastroenterology Available online 30 April 2013

2. Background Crohn’s disease : chronic, progressive, disabling, destructive inflammatory disorder The conventional “step-care” incremental approach : corticosteroids and immunomodulators (thiopurines or methotreate)  No clear effect Cosnes et al. Gut 2005;54:237–241. Irreversible damage?

3. Lakatos et al. Am J Gastroenterol 2012;107:579–588

4. Ramadas et al. Gut 2010;59:1200–1206

6. In adult  Often less severe, toxicity of thiopurines Clinical features associated with high risk of progression to disabling disease Beaugerie et al. Gastroenterology 2006;130:650–656 The Aim Benefits on the 3-year course of CD in high risk of disabling disease Conventional step-care vs early azathioprine

7. Method Randomized, parallel, open-label, 24 centers in France July 12, 2005 ~ November 30, 2010, Age ≥ 18years, diagnosed within 6months High risk for disabling disease Younger than 40 Active perianal lesion Corticosteroid use (<3months) Exclusion criteria Immunomodulators or anti-TNF Immediate need for surgery or anti-TNF therapy Severe comorbidity Infection Renal or liver failure Contraindication to thiopurines Malignancy Histroy of drug abuse Predictable poor complication Pregnant women

8. Azathioprine Group : 2.5 mg ∙ kg -1 ∙ day -1 Conventional management : Change to Azathioprine : corticosteroid dependency chronic active disease (frequent flares, poor response to treatment with corticosteroids, or development of severe perianal disease) Early intolerance to azathioprine - Mercaptopurine Pancreatitis or failure of thiopurines – subcutaneous Methotrexate Flare – Prednisone Fail to response – Anti-TNF (infliximab or adalimumab)

9. Follow up (6, 12 weeks and every 3months) Physical exam, lab tests, CDAI (disease activity), The Inflammatory Bowel Disease Questionnaire (IBDQ) The primary outcome : proportion of trimesters in remission Secondary outcome : proportion of trimester with flare, hospitalization, active perianal disease, perianal surgery, intestinal surgery, corticosteroid use, anti-TNF use

12. 67% 56% P=0.69

16. Conclusion Administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission