[en] [en] OBJECTIVE: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy).
DESIGN: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).
RESULTS: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively).
CONCLUSION: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.
TRIAL REGISTRATION NUMBER: NCT00571337 and NCT02177071.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Pierre, Nicolas ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Huynh-Thu, Vân Anh ; Université de Liège - ULiège > Montefiore Institute of Electrical Engineering and Computer Science
Baiwir, Dominique ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Mazzucchelli, Gabriel ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
Fleron, Maximilien ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie analytique inorganique
Trzpiot, Lisette ; Université de Liège - ULiège > Département de chimie (sciences) > Center for Analytical Research and Technology (CART)
Eppe, Gauthier ; Université de Liège - ULiège > Département de chimie (sciences) > Laboratoire de spectrométrie de masse (L.S.M.)
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences)
Laharie, David ; Service d'Hépato-gastroentérologie et oncologie digestive, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
Satsangi, Jack; Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
Bossuyt, Peter ; Imelda GI Clinical Research Center, Imelda Hospital, Bonheiden, Belgium
Vuitton, Lucine; Department of Gastroenterology, Besançon University Hospital, Besancon, France ; UMR 1098, Franche-Comté University, Besancon, France
Vieujean, Sophie ; Université de Liège - ULiège > Département des sciences cliniques > Hépato-gastroentérologie
Colombel, Jean-Frédéric ; Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
H2020 - 633168 - BIOCYCLE - BIOlogical therapy CYCLEs towards tailored, needs-driven, safer and cost-effective management of Crohn’s disease
Funders :
EU - European Union Walloon region CHU Liège - Central University Hospital of Liege FEDER - Fonds Européen de Développement Régional
Funding text :
This work was supported by the European Union’s Horizon 2020 under the grant agreement N° 633168 — BIOCYCLE (PHC-13-2014), the Walloon Region and the Fond Européen de Développement Régional (FEDER) (Grant portfolio 246099-510388) and internal funding from the Liege University Hospital.
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