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Soluble Mucosal Addressin Cell Adhesion Molecule 1 and Retinoic Acid are Potential Tools for Therapeutic Drug Monitoring in Patients with Inflammatory Bowel Disease Treated with Vedolizumab: A Proof of Concept Study.
Paul, Stephane; Williet, Nicolas; Di Bernado, Thomas; Berger, Anne-Emmanuelle; Boschetti, Gilles; Filippi, Jerome; Del Tedesco, Emilie; Nancey, Stephane; Flourie, Bernard; Roblin, Xavier.
Affiliation
  • Paul S; Department of Immunology, University Hospital of Saint-Etienne, Saint Etienne, France.
  • Williet N; INSERM U1111, CIRI, Lyon, France.
  • Di Bernado T; Groupe Immunité des Muqueuses et Agents Pathogènes [GIMAP], Faculty of Medicine of Saint-Etienne, Saint Etienne, France.
  • Berger AE; Department of Gastroenterology, University Hospital of Saint-Etienne, Saint Etienne, France.
  • Boschetti G; Department of Gastroenterology, University Hospital of Saint-Etienne, Saint Etienne, France.
  • Filippi J; Department of Immunology, University Hospital of Saint-Etienne, Saint Etienne, France.
  • Del Tedesco E; INSERM U1111, CIRI, Lyon, France.
  • Nancey S; Groupe Immunité des Muqueuses et Agents Pathogènes [GIMAP], Faculty of Medicine of Saint-Etienne, Saint Etienne, France.
  • Flourie B; INSERM U1111, CIRI, Lyon, France.
  • Roblin X; Department of Gastroenterology, Lyon Sud Hospital, University Claude Bernard Lyon 1 and Civic Hospices of Lyon, Pierre Benite, France.
J Crohns Colitis ; 12(9): 1089-1096, 2018 Aug 29.
Article in En | MEDLINE | ID: mdl-29860366
ABSTRACT
BACKGROUND AND

AIMS:

Vedolizumab [VDZ], a humanized monoclonal antibody targeting α4ß7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease [IBD] who have not adequately responded to standard therapies, and high vedolizumab trough levels [VTLs] have been associated with clinical remission. The α4ß7 integrin binds to endothelial MAdCAM-1 and is upregulated by retinoic acid [RA]. The aim of this study was to determine the relationships between soluble MAdCAM-1 [sMAdCAM-1] and RA concentrations during clinical remission with VDZ maintenance therapy.

METHODS:

In a retrospective study performed in IBD patients treated with VDZ, we measured VTL, sMAdCAM-1 and RA concentrations.

RESULTS:

Among the 62 included patients [38 Crohn's disease], 24 relapsed and 38 stayed in remission from Weeks 10 to 30 after VDZ initiation. During this maintenance therapy, the median values of VTLs and RA were 15.4 µg/mL and 0.97 ng/mL, respectively, whereas sMAdCAM-1 was undetectable [<0.41 ng/mL] in 67.3% of samples. The positive predictive value [PPV] of undetectable sMAdCAM-1 for clinical remission was 80.0%, with a corresponding sensitivity of 74.6%. On multivariate analysis, undetectable sMAdCAM-1 and high VTLs [>19 µg/mL] were independently associated with clinical remission [OR = 7.5, p = 0.006 and OR = 2.2, p = 0.045, respectively]. The combination of sMAdCAM-1 < 0.41 ng/mL and VTL > 19 µg/mL was the best pharmacokinetic profile, with a PPV of 95.2%. Median values of sMAdCAM-1 and RA were significantly higher [p = 0.0001] before VDZ therapy than during the follow-up [sMAdCAM-1 40.5 vs < 0.41 ng/mL; RA 1.7 vs 0.97 ng/mL]. Only RA > 1.86 ng/mL before VDZ therapy was predictive of clinical remission during the follow-up (Area Under a Receiver Operating Characteristic curve [AUROC] = 80.7%).

CONCLUSIONS:

Undetectable sMAdCAM-1 appears strongly associated with clinical remission during VDZ maintenance therapy. Combination of undetectable sMAdCAM-1 with high VTL is also potentially interesting for therapeutic drug monitoring. Baseline RA concentrations are predictive of clinical remission. These findings need to be confirmed in further prospective studies.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tretinoin / Gastrointestinal Agents / Inflammatory Bowel Diseases / Cell Adhesion Molecules / Drug Monitoring / Antibodies, Monoclonal, Humanized / Mucoproteins Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: J Crohns Colitis Journal subject: GASTROENTEROLOGIA Year: 2018 Document type: Article Affiliation country: France

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tretinoin / Gastrointestinal Agents / Inflammatory Bowel Diseases / Cell Adhesion Molecules / Drug Monitoring / Antibodies, Monoclonal, Humanized / Mucoproteins Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: J Crohns Colitis Journal subject: GASTROENTEROLOGIA Year: 2018 Document type: Article Affiliation country: France