P458 Association between adalimumab serum levels and level of remission in Crohn’s disease

S. Hambli1, S. Rogeau2, N. Duveau3, M. Nachury1, J. Branche1, R. Gérard1, P. Wils1, C. Lauriot Dit Prevost1, T. Lambin1, P. Desreumaux1, M. Labalette2, B. Pariente1

1CHRU Lille, Service des Maladies de l’Appareil Digestif et Nutrition, Lille, France, 2CHRU Lille, Institut d’immunologie, Lille, France, 3Service d’Hépato-Gastro-entérologie, Centre Hospitalier de Roubaix, Roubaix, France

Background

Adalimumab (ADA) is effective as induction and maintenance therapy in Crohn’s disease (CD). Serum ADA levels have been shown to be correlated with clinical remission. Therapeutic goals have evolved based on the notion of ‘treat to target’ and the aim is to achieve deep remission. The objective of this study was to consider the association between serum ADA levels and clinical, biological, endoscopic and iconographic remission in CD.

Methods

From October 1, 2016 to December 31, 2018, all CD patients receiving ADA who had a serum ADA level test with anti-ADA antibodies (AAA) detection were consecutively included. We compared serum ADA levels between the following groups: patients with and without clinical remission, patients with biological remission and those with a CRP >5mg/l, patients with endoscopic remission and those with ulcerations and patients with iconographic remission and those with active radiological lesions. In addition, we defined optimal cut-off values to reach these therapeutic targets by analysing ROC curves.

Results

Three hudred and four patients were included corresponding to a total of 445 assays. Indications for the ADA assay were mainly for persistent disease activity in 308 (69%) samples. An immunosuppressant was initially associated with ADA treatment in 154 (35%) samples and 75 (17%) assays were performed under combotherapy. ADA concentrations were higher in patients who started ADA in combotherapy (8.3 vs. 6.6 μg/ml, p = 0.005), but not in patients treated by combotherapy at the time of dosing (8.7 vs. 7.1 μg/ml, p = 0.12). Serum levels of ADA were significantly higher in patients in remission compared with patients with active disease for clinical remission (7.9 vs. 6.3 μg/ml, p = 0.015), biological remission (9.5 vs. 5.1 μg/ml, p <0.001), endoscopic remission (10.1 vs. 6.1 μg/ml, p <0.001) and luminal iconographic remission (9.1 vs. 6.8 μg/ml, p = 0.04). ROC curves and the areas under the curve (ASC) were analysed to determine optimal cut-off values of serum ADA levels to predict these different levels of remission: 6.45 μg/ml (AUC 0, 56, p = 0.027) for clinical remission, 7.35 μg/ml (AUC 0.67, p < 0.001) for biological remission, 9.75 μg/ml (AUC 0.64, p = 0.002) for endoscopic remission and 7.80 μg/ml (AUC 0.58, p = 0.04) for luminal iconographic remission.

Conclusion

High levels of ADA are associated with clinical, biological, endoscopic and iconographic remission in CD. Optimal cut-off values of ADA have been identified and increase as deep remission is obtained. These results suggest that serum ADA levels should be considered to be one of the tools in the tight control strategy of CD and adapted according to pre-defined objectives (clinical, biological or mucosal).