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OC-072 The Toppic Trial: A Randomised, Double-Blind Parallel Group Trial of Mercaptopurine VS Placebo to Prevent Recurrence of Crohn’s Disease Following Surgical Resection in 240 Patients
  1. I Arnott1,
  2. C Mowat2,
  3. H Ennis3,
  4. C Keerie3,
  5. S Lewis3,
  6. A Cahill4,
  7. J Morris4,
  8. M Dunlop5,
  9. S Bloom6,
  10. J Lindsay7,
  11. S Subramanian8,
  12. J Satsangi1,
  13. on behalf of TOPPIC Trial Study Group
  1. 1Gastroenterology, NHS Lothian, Edinburgh
  2. 2Gastroenterology, NHS Tayside, Dundee
  3. 3Edinburgh Clinical Trials Unit, University of Edinburgh, Edinburgh
  4. 4Gastroenterology, NHS Greater Glasgow and Clyde, Glasgow
  5. 5Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh
  6. 6Gastroenterology, University College London Hospital
  7. 7Gastroenterology, Royal London Hospital, London
  8. 8Gastroenterology, Royal Liverpool Hospital, Liverpool, UK

Abstract

Introduction Up to 65% of patients with Crohn’s disease (CD) require an operation to control the disease within the first ten years of the condition. This study assessed whether the use of mercaptopurine (MP) can prevent or delay post-operative recurrence in CD.

Methods In this randomised, placebo-controlled, double-blind, parallel group trial patients with a confirmed diagnosis of CD undergoing intestinal resection were recruited from 29 UK hospitals. Following informed consent, each patient was randomised to receive a daily oral dose of MP or placebo. Dose was adjusted by weight and thiopurine methyltransferase (TPMT) status and safety monitoring was blinded. Treatment was for a maximum of 36 months. The primary endpoint was defined by clinical recurrence of CD (CDAI > 150 plus 100 point rise) and the need for anti-inflammatory rescue therapy or primary surgical intervention. Secondary endpoints included endoscopic recurrence.

Results 240 patients (median age 38 years, 60.8% female, 22.9% smokers were enrolled and received at least one dose of study drug. 128 (53%) were randomised to receive MP and 112 (47%) to placebo. No randomised patients were excluded from the analysis. More patients reached primary endpoint within the placebo (n = 26,23.2%) vs MP groups (n = 16,12.5%) with an adjusted p-value of 0.073 (Hazard Ratio (HR) 0.535, 95% CI 0.27–1.06) and an unadjusted p value of 0.046 (HR 0.527, 95% CI 0.28–0.99) Smokers were more likely to reach primary endpoint than non-smokers (p = 0.018 (HR 0.127,95% CI 0.04–0.46 NNT = 3 amongst smokers, HR 0.898, 95% CI 0.42–1.94 NNT = 31 amongst non-smokers). Smoking habit (HR 2.06, 1.09–3.90) but not age at diagnosis, duration of disease, sex, previous surgery or previous thiopurine or anti-TNF exposure predicted primary outcome. A higher proportion of patients on MP compared with placebo maintained complete endoscopic remission (Rutgeerts i0) at weeks 49 (29.7 v 14.4%, p = 0.006), and 157 (22.5% v 12.5%, p = 0.041) on post-hoc analysis.

Conclusion TOPPIC is the largest, double-blind trial of thiopurines to prevent post-operative recurrence in CD. MP modestly reduces the frequency of clinical post-operative recurrence of CD. This was significant amongst smokers, but not in non-smokers. Adverse events did not differ between groups.

Disclosure of Interest None Declared

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