P388 Prediction model to safely CEASE anti-TNF therapy in Crohn’s disease: validation of a predictive diagnostic tool for the cessation of anti-TNF treatment in CD in a Dutch population
S. Ten Bokkel Huinink1, D. de Jong2, J. van der Woude1, D. Nieboer3, E. Steyerberg4, F. Wolfhagen5, B. van Tuyl6, R. West7, T. Romkens8, A. Tan9, F. Hoentjen10, W. Mares11, A. Bodelier12, G. Dijkstra13, R. Mallant14, N. de Boer15, J. Reinders16, P. van Boeckel17, G. Tack18, M. Duijvestein15, G. D’Haens2, A. de Vries1
1Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands, 2Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands, 3Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands, 4Department of Clinical Biostatistics and Medical Decision Makin, Leiden University Medical Center, Leiden, The Netherlands, 5Gastroenterology and Hepatology, Albert Schweitzer Hospital, Dordrecht, The Netherlands, 6Diakonessenhuis, Gastroenterology and Hepatology, Utrecht, The Netherlands, 7Franciscus Gasthuis and Vlietland, Gastroenterology and Hepatology, Rotterdam, The Netherlands, 8Gastroenterology and Hepatology, Jeroen Bosch Hospital, Den Bosch, The Netherlands, 9Gastroenterology and Hepatology, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands, 10Gastroenterology and Hepatology, Radboudumc, Nijmegen, The Netherlands, 11Gastroenterology and Hepatology, Gelderse Vallei Hospital, Ede-Wageningen, The Netherlands, 12Gastroenterology and Hepatology, Amphia Hospital, Breda, The Netherlands, 13Gastroenterology and Hepatology, University Medisch Centrum Groningen, Groningen, The Netherlands, 14Gastroenterology and Hepatology, Flevo Hospital, Almere, The Netherlands, 15Amsterdam University Medical Center, VU University Medical Center- AG&M Research Institute, Amsterdam, The Netherlands, 16Gastroenterology and Hepatology, Haga Hospital, Den Haag, The Netherlands, 17Gastroenterology and Hepatology, St. Antonius Hospital, Nieuwegein, The Netherlands, 18Gastroenterology and Hepatology, Medical Center Leeuwarden, Leeuwarden, The Netherlands
Background
Tools for patient identification to safely cease anti-TNF therapy in Crohn’s disease (CD) patients are urgently needed. After an individual participant data meta-analysis (IPD-MA) a predictive diagnostic tool has been developed for cessation of anti-TNF therapy in CD. This study aims to validate this tool.
Methods
A retrospective study was conducted, in 16 Dutch Hospitals, of CD patients in whom anti-TNF therapy was ceased. Inclusion criteria were anti-TNF therapy use >6 months, start of anti-TNF therapy due to luminal CD and remission as an indication for cessation. Collected baseline demographic, clinical, biochemical, treatment and imaging data were included; age, gender, smoking, Montreal classification, disease- and remission duration, history of surgery, type of anti-TNF medication, previous or concomitant immunosuppressant, thiopurines level, previous anti-TNF therapy, anti-TNF therapy duration, haemoglobin, leukocytes, thrombocytes, albumin, C-reactive protein, anti-TNF serum concentration, anti-infliximab/adalimumab antibodies, remission at MRI/endoscopy, additional stop reason other than remission. The primary outcome was documented relapse of CD that necessitated (re)introduction of biologicals, corticosteroids or immune-suppressants or surgery.
Results
A total of 523 CD patients (333 females (63%), median age 40 years (IQR 32 – 53)) were included. 293 (56%) patients experienced a relapse after anti-TNF cessation after a median follow-up of 30.2 months (IQR 15–51). The relapse rate was 33% (95% CI 31–34) and 53% (95% CI 52–53) after 1 and 2 years, respectively. The discriminative ability of the prediction model in this external validation cohort (Table 1) equalled that of a previous IPD-MA with a C-statistic of 0.59. An update of the model with faecal calprotectin resulted in a C-statistic of 0.60 [0.55–0.63] and a reported calibration slope of 0.69.
| Age | 0.99 (0.97–0.99) |
| No smoking | 0.72 (0.59–0.87) |
| Montreal A2 | 0.67 (0.51–0.87) |
| Montreal A3 | 0.75 (0.51–0.87) |
| No montreal L4 | 0.81 (0.59–1.09) |
| No immunosuppressant at baseline | 1.43 (1.40–1.46) |
| Disease duration | 1.01 (0.99–1.03) |
| No previous anti-TNF | 0.81 (0.59–1.11) |
| Anti-TNF type adalimumab | 1.22 (0.99–1.51) |
| Platelets at baseline | 1.12 (1.00–1.25) |
| Endoscopic remission | 0.92 (0.65–1.30) |
Conclusion
A previously developed predictive diagnostic tool to safely cease anti-TNF therapy in CD has been validated, however, showed moderate performance in this external cohort. A further update of the model with biochemical and histological data is necessary to improve our ability to adequately select patients for cessation of anti-TNF therapy and is currently being performed.