Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease

Remi Mahmoud; Edo H J Savelkoul; Wout Mares; Rogier Goetgebuer; Ben J M Witteman; Daan B de Koning; Sebastiaan A C van Tuyl; Itta Minderhoud; Maurice W M D Lutgens; Dilek Akol-Simsek; Fiona D M van Schaik; Herma H Fidder; Jeroen M Jansen; Petra G A van Boeckel; Nofel Mahmmod; Carmen S Horjus-Talabur Horje; Tessa E H Römkens; Jean-Frédéric Colombel; Frank Hoentjen; Bindia Jharap; Bas Oldenburg; Dutch Initiative on Crohn’s and Colitis (ICC) and the AWARE study group

doi:10.1016/j.cgh.2022.08.024

Complete Endoscopic Healing Is Associated With Lower Relapse Risk After Anti-TNF Withdrawal in Inflammatory Bowel Disease

Clin Gastroenterol Hepatol. 2023 Mar;21(3):750-760.e4. doi: 10.1016/j.cgh.2022.08.024. Epub 2022 Aug 31.

Authors

Remi Mahmoud¹, Edo H J Savelkoul², Wout Mares³, Rogier Goetgebuer⁴, Ben J M Witteman³, Daan B de Koning⁵, Sebastiaan A C van Tuyl⁶, Itta Minderhoud⁷, Maurice W M D Lutgens⁸, Dilek Akol-Simsek⁹, Fiona D M van Schaik¹, Herma H Fidder¹, Jeroen M Jansen¹⁰, Petra G A van Boeckel¹¹, Nofel Mahmmod¹¹, Carmen S Horjus-Talabur Horje¹², Tessa E H Römkens¹³, Jean-Frédéric Colombel¹⁴, Frank Hoentjen¹⁵, Bindia Jharap¹⁶, Bas Oldenburg¹⁷; Dutch Initiative on Crohn’s and Colitis (ICC) and the AWARE study group

Affiliations

¹ Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands.
² Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
³ Department of Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede, The Netherlands.
⁴ Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands.
⁵ Department of Gastroenterology and Hepatology, Gelre Hospital, Apeldoorn, The Netherlands.
⁶ Department of Gastroenterology and Hepatology, Diakonessenhuis, Utrecht, The Netherlands.
⁷ Department of Gastroenterology and Hepatology, Tergooi Medical Center, Hilversum, The Netherlands.
⁸ Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands.
⁹ Department of Gastroenterology and Hepatology, DC klinieken, Apeldoorn, The Netherlands.
¹⁰ Department of Gastroenterology and Hepatology, Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam, The Netherlands.
¹¹ Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, The Netherlands.
¹² Department of Gastroenterology and Hepatology, Rijnstate Hospital, Arnhem, The Netherlands.
¹³ Department of Gastroenterology and Hepatology, Jeroen Bosch Hospital, 's-Hertogenbosch, The Netherlands.
¹⁴ Department of Medicine, Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, New York.
¹⁵ Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands; Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, Canada.
¹⁶ Department of Gastroenterology and Hepatology, Meander Medical Center, Amersfoort, The Netherlands.
¹⁷ Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: boldenbu@umcutrecht.nl.

PMID: 36055567
DOI: 10.1016/j.cgh.2022.08.024

Abstract

Background & aims: Discontinuation of anti-tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing.

Methods: This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3-4) versus complete (Mayo 0/SES-CD 0-2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use.

Results: Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6-2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43-7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01-0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months.

Conclusions: The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse.

Keywords: Biologicals; De-escalation; Deep Remission; Endoscopic Remission.

Publication types

Multicenter Study

MeSH terms

Adult
Chronic Disease
Colitis, Ulcerative* / drug therapy
Crohn Disease* / drug therapy
Humans
Inflammatory Bowel Diseases* / drug therapy
Infliximab / therapeutic use
Mesalamine / therapeutic use
Prospective Studies
Recurrence
Remission Induction
Tumor Necrosis Factor Inhibitors / therapeutic use

Substances

Tumor Necrosis Factor Inhibitors
Mesalamine
Infliximab