P309 Withdrawal of thiopurines in Inflammatory Bowel Disease patients in stable remission: a prospective, multicentre cohort study
Authors: Savelkoul E , Mahmoud R , De Jong D , Van Dop W , Römkens T , Nissen L , Mahmmod N , Van Boeckel P , Lutgens M , Mares W , Epping L , Minderhoud I , Jansen J , Gisbertz I , Boekema P , De Koning D , Horjus C , Jharap B , Oldenburg B , Hoentjen F 
Published: January 2022

Abstract

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) &gt;, 4 for Crohn’s disease (CD) or endoscopic Mayo &gt;, 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.