DOP70 Anti-TNF withdrawal according to a risk-stratified protocol does not reduce the risk of relapse in patients with Inflammatory Bowel Disease in endoscopic remission: A prospective study
Mahmoud, R.(1);Savelkoul, E.(2);Mares, W.(3);Goetgebuer, R.(4,5);Witteman, B.(3);de Koning, D.(6);Minderhoud, I.(7);van Tuyl, S.(8);van Boeckel, P.(9);Mahmmod, N.(9);Lutgens, M.(10);Horjus, C.(11);Römkens, T.(12);Akol-Simsek, D.(13);Jansen, J.(14);Hoentjen, F.(2,15);Jharap, B.(16);Oldenburg, B.(1);
(1)University Medical Centre Utrecht, Department of Gastroenterology and Hepatology, Utrecht, The Netherlands;(2)Radboud University Medical Centre, Department of Gastroenterology and Hepatology, Nijmegen, The Netherlands;(3)Gelderse Vallei Hospital, Department of Gastroenterology and Hepatology, Ede, The Netherlands;(4)Erasmus Medical Centre, Department of Gastroenterology and Hepatology, Rotterdam, The Netherlands;(5)Amsterdam University Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(6)Gelre Hospital, Department of Gastroenterology and Hepatology, Apeldoorn, The Netherlands;(7)Tergooi Medical Centre, Department of Gastroenterology and Hepatology, Hilversum, The Netherlands;(8)Diakonessenhuis, Department of Gastroenterology and Hepatology, Utrecht, The Netherlands;(9)St. Antonius Hospital, Department of Gastroenterology and Hepatology, Nieuwegein, The Netherlands;(10)Elisabeth-TweeSteden Hospital, Department of Gastroenterology and Hepatology, Tilburg, The Netherlands;(11)Rijnstate Hospital, Department of Gastroenterology and Hepatology, Arnhem, The Netherlands;(12)Jeroen Bosch Hospital, Department of Gastroenterology and Hepatology, 's-Hertogenbosch, The Netherlands;(13)Medical Centre de Veluwe, Department of Gastroenterology and Hepatology, Apeldoorn, The Netherlands;(14)Onze Lieve Vrouwe Gasthuis OLVG, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands;(15)University of Alberta, Division of Gastroenterology- Department of Medicine, Edmonton, Canada;(16)Meander Medical Centre, Department of Gastroenterology and Hepatology, Amersfoort, The Netherlands; AWARE study group Dutch Initiative on Crohn's and Colitis
Background
Discontinuation of anti-tumour necrosis factor alpha agents (anti-TNF) in patients with inflammatory bowel disease (IBD) in remission may reduce side effects and costs, but this has to be weighed against the risk of relapse. We developed a risk-stratified protocol for anti-TNF withdrawal, and aimed to assess the risk of relapse after risk-stratified anti-TNF withdrawal.
Methods
This was a single arm prospective observational cohort study. Patients were recruited between September 2018-2020 in 13 hospitals in the Netherlands. Inclusion criteria were a diagnosis of IBD, age >18 years, elective anti-TNF withdrawal in a patient with quiescent disease (according to the treating physician), no current or planned use of vedolizumab, ustekinumab or tofacitinib, no hospitalization, and no active or planned pregnancy. According to the protocol, patients were recommended to withdraw anti-TNF only when in endoscopic remission either without high-risk criteria (age at diagnosis <18 years, and for Crohn’s disease [CD]: smoking, stricturing/penetrating disease behaviour, small bowel resection >50cm), or when trough levels were undetectable. We constructed Kaplan-Meier curves with log-rank test to compare the risk of relapse in patients who discontinued anti-TNF in accordance with, versus against, the protocol. Cox regression analysis was performed to identify predictors of relapse.
Results
We enrolled 115 patients (CD: n=61, 53%), with a median follow-up time of 1.9 (IQR 1.8 – 2.1) years. Baseline endoscopic remission was confirmed in 103 (89.6%) patients, and 35 (30.4%) patients continued an immunomodulator. During follow-up, 57 (49.6%) patients relapsed (Figure 1). The relapse rate was similar in patients in endoscopic remission who withdrew anti-TNF in according with, versus against, the protocol (50.7% versus 44.4%, p=0.65), and in patients with versus without an immunomodulator (hazard rate [HR] 0.89, 95%CI 0.50 – 1.59), but was lower in patients with subtherapeutic anti-TNF trough levels (adjusted HR: 0.55, 95%CI: 0.31 – 0.99), and in patients with UC/IBD-unclassified (IBDU) who were treated with mesalamine maintenance therapy (HR: 0.35, 95%CI 0.13 – 0.94). Anti-TNF was reintroduced in 41 (71.9%) patients, with remission rates of 64.5% and 81.8% at 3 and 12 months, respectively. In 6 (15.0%) patients anti-TNF therapy was discontinued again due to primary non-response or loss of response.
Conclusion
The risk of relapse after anti-TNF withdrawal remains high in a strictly selected group of patients with uncomplicated IBD in endoscopic remission. Therapeutic drug monitoring prior to anti-TNF withdrawal, and mesalamine therapy for patients with UC or IBDU, may reduce the risk of relapse.