OP37 Is the withdrawal of anti-tumour necrosis factor in inflammatory bowel disease patients in remission feasible without increasing the risk of relapse? Results from the randomised clinical trial of GETECCU (EXIT)

Abstract

Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for > 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC >250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

Biological therapy for inflammatory bowel disease: cyclical rather than lifelong treatment?

“…Small numerical difference in relapse (13% vs 6%) and endoscopic lesions (19% vs 8%) were not significant. There was, however, a significant difference in the proportion of patients with a faecal calprotectin >250 µg/g (33% vs 14%) 16. As this study stands in contrast to the other RCT results, we should acknowledge that the numerical differences at 12 months may have led to significant differences at a later time point especially as the faecal calprotectin rose more often in the withdrawal group 16…”

“…There was, however, a significant difference in the proportion of patients with a faecal calprotectin >250 µg/g (33% vs 14%). 16 As this study stands in contrast to the other RCT results, we should acknowledge that the numerical differences at 12 months may have led to significant differences at a later time point especially as the faecal calprotectin rose more often in the withdrawal group. 16 Observational data on the risk of anti-TNF discontinuation in patients with CD have been examined by several meta-analyses.…”

“…15 In contrast, the Spanish EXIT study found no increased risk of relapse in a placebo controlled randomised controlled trial of anti-TNF withdrawal in 140 patients with IBD in clinical and endoscopic remission who were all on immunomodulators. 16 At 12 months, sustained clinical remission occurred in 76% of the withdrawal and 84% of the maintenance arm (p=NS). Small numerical difference in relapse (13% vs 6%) and endoscopic lesions (19% vs 8%) were not significant.…”

“…Patients were randomised to continue infliximab or to receive a similar placebo (only study with full blinding) with relapse rates of 0% and 49% after 1 year 15. In contrast, the Spanish EXIT study found no increased risk of relapse in a placebo controlled randomised controlled trial of anti-TNF withdrawal in 140 patients with IBD in clinical and endoscopic remission who were all on immunomodulators 16. At 12 months, sustained clinical remission occurred in 76% of the withdrawal and 84% of the maintenance arm (p=NS).…”

Morbus Crohn Update

“…Nach Absetzten von Infliximab oder Adalimumab (Patienten in Remission mit fäkalem Calprotectin < 250 mg/g für > 6 Monate, SES-CD < 5, max. 1 oberflächlichem Ulkus von < 10 % Oberflächenbeteiligung in einem Segment, MRT ohne Darmwandödem und fehlender perianaler Beteiligung) blieben nach 1 Jahr 76 % in klinischer Remission; im Vergleich zu 84 % der Patienten unter fortgeführter Therapie [75].…”