Observational Study
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World J Gastroenterol. Mar 7, 2022; 28(9): 961-972
Published online Mar 7, 2022. doi: 10.3748/wjg.v28.i9.961
Relationship between clinical remission of perianal fistulas in Crohn’s disease and serum adalimumab concentrations: A multi-center cross-sectional study
Laura Sirmai, Anne-Laure Pelletier, Nathalie Gault, Camille Zallot, Guillaume Bouguen, Dominique Bouchard, Pascale Roland Nicaise, Marine Peyneau, Sandrine Sironneau, Marcelo De Carvalho Bittencourt, Antoine Petitcollin, Pedro Fernandez, Xavier Roblin, Laurent Siproudhis, Laurent Abramowitz
Laura Sirmai, Anne-Laure Pelletier, Division of Hepato-Gastroenterology and Digestive Oncology, Bichat Claude Bernard University Hospital, Paris 75018, France
Laura Sirmai, Division of Hepato-Gastroenterology, Hospital Croix Saint Simon, Paris 75020, France
Nathalie Gault, Division of Epidemiology, Biostatistics and Clinical Research, University Hospital Center Bichat, Paris 75018, France
Nathalie Gault, National Institute of Health and Medical Research CIC-EC1425, University Hospital Center Bichat, Paris 75018, France
Camille Zallot, Division of Gastroenterology, Nancy Regional and University Hospital Center, Nancy 54035, France
Guillaume Bouguen, Laurent Siproudhis, Imphy CIC 1414 Group and Division of Gastroenterology and Hepatology, University Hospital of Rennes, Pontchaillou, Rennes 35033, France
Dominique Bouchard, Division of Proctology, Hospital Bagatelle, Talence 33400, France
Pascale Roland Nicaise, Marine Peyneau, Division of Immunology, University Hospital Center Bichat, Paris 75018, France
Marine Peyneau, Inflammation, Microbiome and Immunosurveillance, Faculty of Pharmacy, Université Paris-Saclay, Châtenay-Malabry 92290, France
Sandrine Sironneau, Division of Radiology, Bagatelle Hospital Center, Talence 33400, France
Marcelo De Carvalho Bittencourt, Division of Immunology, Nancy Regional and University Hospital Center, Nancy 54000, France
Marcelo De Carvalho Bittencourt, University of Lorraine, CNRS UMR 7365, IMoPA, Nancy 54000, France
Antoine Petitcollin, Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Center, Rennes University Hospital, Rennes 35700, France
Pedro Fernandez, Division of Radiology, University Hospital Center Bichat, Paris 75018, France
Pedro Fernandez, Orangerie Center, Le Perreux-sur-Marne 94170, France
Xavier Roblin, Division of Gastroenterology, CHU Saint Etienne, Saint-Priest-en-Jarez 42270, France
Laurent Abramowitz, Division of Gastroenterology and Hepatology and Proctology, University Hospital Center Bichat, Paris 75018, France
Laurent Abramowitz, Ramsay GDS Clinique Blomet, Paris 75018, France
Author contributions: Sirmai L is the Guarantor of the article; Sirmai L conceived the study together with Pelletier AL and Abramowitz L; Fernandez P read the MRI images; Sirmai L, Pelletier AL, Zallot C, Bouguen G, Bouchard D, Roland Nicaise P, Peyneau M, Sironneau S, De Carvalho Bittencourt M, Petitcollin A, Roblin X, Siproudhis L, and Abramowitz L collected data; Gault N performed statistical analyses; all authors commented the article and approved the final version of the article, including the authorship list.
Supported by the Assistance Publique des Hôpitaux de Paris and AbbVie (North Chicago, Illinois, United States).
Institutional review board statement: The study was reviewed and approved by the CNIL (N° CERFA 13810*01).
Conflict-of-interest statement: Sirmai L reports having received grant support from Abbvie and congress invitations from Roche and Sandoz and having received conference or consultancy fees from Gilead, MSD, Abbvie, Mayoly Spindler, Takeda, Ipsen, Allergan France and Ferring; Pelletier AL reports having received grant support from Abbvie and financial support from Ferring; Zallot C reports having received financial support from Takeda, Abbvie, Ferring, Janssen and Pfizer; Bouguen G reports having received lecture fees from Abbvie, Ferring, MSD, Takeda and Pfizer and consultant fees from Takeda, Janssen, Mylan and Abbvie; Bouchard D reports having received speaking fees from Abbvie, MSD and Janssen, consultancy fees from Takeda, and congress invitations from Abbvie, Pfizer and Takeda; Gault N, Roland Nicaise P, Peyneau M, Sironneau S, Bittencourt M, Petitcollin A, Fernandez P all declare they have no conflicts of interest; Roblin X reports having received financial support from Abbvie, Amgen, Pfizer, Takeda, Janssen, MSD and Theradiag; Siproudhis L reports having received conference or consultancy fees from Gilead, MSD, Abbvie, Mayoly Spindler, Takeda, Ipsen, Allergan France and Ferring; Abramowitz L reports having received grant support from Abbvie and financial support from Takeda.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Laura Sirmai, MD, Doctor, Division of Hepato-Gastroenterology and Digestive Oncology, Bichat Claude Bernard University Hospital, 46 Rue Henri Huchard, Paris 75018, France. laura.sirmai@gmail.com
Received: February 11, 2021
Peer-review started: February 11, 2021
First decision: March 28, 2021
Revised: April 25, 2021
Accepted: January 29, 2022
Article in press: January 29, 2022
Published online: March 7, 2022
Processing time: 384 Days and 10.5 Hours
Abstract
BACKGROUND

Crohn’s disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients.

AIM

To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

METHODS

This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present’s criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events.

RESULTS

The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) μg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) μg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations.

CONCLUSION

We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Keywords: Crohn’s disease; Clinical pharmacology; Peri-anal disorders; Adalimumab

Core Tip: Perianal fistulas (PAFs) are a complication of Crohn’s disease (CD) in approximately 20% of patients. Adalimumab (ADA) was shown to treat CD-associated PAFs; however, little information is available on serum ADA concentrations and their remission. We performed a cross-sectional study at four hospitals in France to investigate this relationship, including 34 patients with 56 evaluations. Fifteen patients had clinical remission (44%). Serum ADA concentrations were significantly higher in evaluations showing clinical remission compared to those without. Thus, ADA serum concentrations that are required for PAF remission should be higher compared with the previously described concentrations associated with luminal remission.