P309 Withdrawal of thiopurines in Inflammatory Bowel Disease patients in stable remission: a prospective, multicentre cohort study
Savelkoul, E.(1);Mahmoud, R.(2);De Jong, D.(1);Van Dop, W.(1);Römkens, T.(3);Nissen, L.(3);Mahmmod, N.(4);Van Boeckel, P.(4);Lutgens, M.(5);Mares, W.(6);Epping, L.(7);Minderhoud, I.(8);Jansen, J.(9);Gisbertz, I.(10);Boekema, P.(11);De Koning, D.(12);Horjus, C.(13);Jharap, B.(14);Oldenburg, B.(2);Hoentjen, F.(15);
(1)Radboud University Medical Centre, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands;(2)University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, The Netherlands;(3)Jeroen Bosch Hospital, Department of Gastroenterology and Hepatology, 's-Hertogenbosch, The Netherlands;(4)St. Antonius Hospital, Department of Gastroenterology and Hepatology, Nieuwegein, The Netherlands;(5)Elisabeth-TweeSteden Hospital, Department of Gastroenterology and Hepatology, Tilburg, The Netherlands;(6)Gelderse Vallei Hospital, Department of Gastroenterology and Hepatology, Ede, The Netherlands;(7)Pantein Hospital, Department of Gastroenterology and Hepatology, Boxmeer, The Netherlands;(8)Tergooi Medical Centre, Department of Gastroenterology and Hepatology, Hilversum, The Netherlands;(9)Onze Lieve Vrouwe Gasthuis OLVG, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(10)Bernhoven Hospital, Department of Gastroenterology and Hepatology, Uden, The Netherlands;(11)Máxima Medical Centre, Department of Gastroenterology and Hepatology, Veldhoven, The Netherlands;(12)Gelre Hospital, Department of Gastroenterology and Hepatology, Apeldoorn, The Netherlands;(13)Rijnstate Hospital, Department of Gastroenterology and Hepatology, Arnhem, The Netherlands;(14)Meander Medical Centre, Department of Gastroenterology and Hepatology, Amersfoort, The Netherlands;(15)University of Alberta, Division of Gastroenterology- Department of Medicine, Edmonton, Canada; The AWARE study group and the Dutch Initiative on Crohn’s and Colitis
Background
Thiopurines including azathioprine [AZA], mercaptopurine [MP] and tioguanine [TG] are cornerstone therapies in the maintenance treatment of inflammatory bowel diseases (IBD). Withdrawal in patients in stable remission may reduce the risk of infections and malignancies, but little is known about the subsequent risk of relapse. This study aimed to assess the relapse rate after discontinuation of thiopurines in IBD patients in stable remission.
Methods
Patients with IBD discontinuing thiopurine therapy were prospectively included in 14 Dutch hospitals if they used a thiopurine for at least one year, and were in steroid-free clinical remission for one year or longer. Clinical, biochemical, endoscopic and radiological data were collected at baseline (thiopurine cessation), and at 3, 6, 12 and 24 months thereafter. The primary endpoint was disease relapse, defined as: induction or escalation of therapy, or, if available, endoscopic activity, indicated by simple endoscopic score (SES-CD) > 4 for Crohn’s disease (CD) or endoscopic Mayo > 1 for ulcerative colitis and IBD unclassified (UC/IBDU). Cox regression analysis was used to determine predictors of relapse.
Results
We enrolled 134 patients (94 CD [70%]; AZA 56%, MP 20%, TG 25%) with a median age of 44.0 years (IQR 30.8-59.0). Fifty-three (40%) patients received concomitant anti-tumour necrosis factor alpha (anti-TNF) at baseline. The median therapy duration before cessation was 61.5 months (IQR 40.0-111.0), median time of clinical remission before cessation was 43.5 months (IQR 27.8-65.5). During the median follow-up time of 14.0 (IQR 11.9-19.7) months after cessation, 37 (28%) patients relapsed (Figure 1). Relapse rates at 12 and 24 months were 28% and 40%, respectively. Median time to relapse was 10.9 (IQR 5.5-16.5) months. UC/IBDU patients had a higher risk of relapse (HR 2.603 [95% CI 1.364 -4.965], p=0.004). Relapse free survival probability in patients with and without concomitant anti-TNF was not significantly different (anti-TNF 82%, no anti-TNF 87%, log rank=0.494, Figure 2). Type of thiopurine, concomitant 5-ASA, remission duration, therapy duration before cessation, baseline mucosal healing, and baseline faecal calprotectin were not predictive of relapse. After relapse, 27 patients received steroids (18 budesonide, 9 prednisone), 15 (re)started thiopurines, 8 initiated anti-TNF, and 8 intensified concomitant anti-TNF.
Figure 1
Figure 2
Conclusion
This prospective study showed relapse rates of 28% and 40% at 12 and 24 months, respectively, after cessation of thiopurines for stable remission. UC/IBDU patients had a higher risk of relapse. Type of thiopurine, remission duration, concomitant 5-ASA or anti-TNF were not predictive of continuing remission.