Infliximab Exposure Associates With Radiologic Evidence of Healing in Patients With Crohn's Disease
Bossuyt, Peter; Dreesen, Erwin; Rimola, Jordi; Devuysere, Sofie; De Bruecker, Yves; Vanslembrouck, Ragna; Laurent, Valérie; Zappa, Magaly; Savoye-Collet, Céline; Pariente, Benjamin; Filippi, Jérôme; Baert, Filip; D'Haens, Geert; Laharie, David; Peyrin-Biroulet, Laurent; Vermeire, Séverine; Lambrecht, Guy; Buisson, Anthony; Bouhnik, Yoram; Woude, Janneke Vander; Van Hootegem, Philippe; Moreau, Jacques; Louis, Edouard; Franchimont, Denis; De Vos, Martine; Mana, Fazia; Brixi, Hedia; Allez, Matthieu; Caenepeel, Philip; Aubourg, Alexandre; Oldenburg, Bas; Pierik, Marieke; Chevret, Sylvie
(2021) Clinical Gastroenterology and Hepatology, volume 19, issue 5, pp. 947 - 954.e2
(Article)
Abstract
Background & Aims: Higher infliximab trough levels are associated with clinical and endoscopic remission in patients with Crohn's disease (CD). We investigated pharmacodynamic features of infliximab and radiological healing. Methods: We performed a substudy of the TAILORIX trial (patients with active luminal CD in Europe, treated with infliximab), analyzing baseline
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and week 54 magnetic resonance enterography (MRE) data. MREs were scored using the MaRIA score by blinded central readers. Radiologic response and remission were defined, based on MaRIA criteria in all segments, as scores below 11 and 7, respectively. We collected data on infliximab trough levels, biomarkers, and endoscopic findings. Our primary aim was to evaluate pharmacodynamic features associated with radiologic response and remission, based on MRE assessments at baseline and at 54 weeks after initiation of infliximab therapy. Results: We analyzed data from 36 patients (50% female; median age 35.7 years; interquartile age range, 25.6–48.6 years; median disease duration, 1.5 months; interquartile duration range, 0.6–22.4 months). At week 54 of treatment, 36.4% of patients had a radiologic response, 30.3% of patients were in remission, and 71% had endoscopic features of remission. At baseline, there was a correlation between the CD endoscopic index of severity and MaRIA scores (κ = 0.46; P = .008), but we found no correlation at week 54 (κ = 0.06; P =. 75). Radiologic remission correlated with infliximab trough level at week 14 (P = .049) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.74; 75% sensitivity; 86% specificity; 90% negative predictive value; 57% positive predictive value). Radiologic response correlated with infliximab trough levels at week 14 (P = .048) when the infliximab trough level cut-off value was set at 7.8 μg/mL (area under the curve, 0.73; 70% sensitivity; 90% specificity; 86% negative predictive value; 78% positive predictive value) and with continuous pharmacologic evidence of response (infliximab trough levels above 5.0 μg/mL at all time points) (P = .034). Conclusions: In a substudy of data from the TAILORIX trial of patients with active luminal CD, we identified a relationship between exposure to infliximab and radiologic evidence of outcomes.
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Keywords: Anti-TNF Agent, Biomarker, Prognostic Factor, Response to Therapy, TAILORIX, Prospective Studies, Humans, Middle Aged, Male, Treatment Outcome, Magnetic Resonance Imaging, Gastrointestinal Agents/therapeutic use, Adult, Female, Infliximab/therapeutic use, Crohn Disease/diagnostic imaging, Gastroenterology, Hepatology, Journal Article
ISSN: 1542-3565
Publisher: W.B. Saunders Ltd
Note: Funding Information: The authors thank Sabrina Williams and Marie-Jo Bertin from the GETAID office for their support in organizing this study, all local investigators and study coordinators who helped with the patient recruitment and follow-up, and all the patients who participated in this study. TAILORIX study group: Guy Lambrecht, Anthony Buisson, Yoram Bouhnik, Janneke Vander Woude, Philippe Van Hootegem, Jacques Moreau, Edouard Louis, Denis Franchimont, Martine De Vos, Fazia Mana, Hedia Brixi, Matthieu Allez, Philip Caenepeel, Alexandre Aubourg, Bas Oldenburg, Marieke Pierik, and Sylvie Chevret. Peter Bossuyt, MD (Conceptualization: Lead; Data curation: Lead; Formal analysis: Lead; Investigation: Lead; Methodology: Lead; Project administration: Lead; Validation: Lead; Writing – original draft: Lead; Writing – review & editing: Lead), Erwin Dreesen (Data curation: Supporting; Formal analysis: Supporting; Methodology: Supporting; Validation: Supporting; Writing – review & editing: Supporting), Jordi Rimola (Data curation: Supporting; Methodology: Supporting; Validation: Supporting; Writing – review & editing: Supporting), Sofie Devuysere (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Yves De Bruecker (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Ragna Vanslembrouck (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Valérie Laurent (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Magaly Zappa (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Celine Savoye-Collet (Data curation: Supporting; Investigation: Supporting; Writing – review & editing: Supporting), Benjamin Pariente (Data curation: Supporting; Writing – review & editing: Supporting), Jérôme Filippi (Data curation: Supporting; Writing – review & editing: Supporting), Filip Baert (Data curation: Supporting; Writing – review & editing: Supporting), Geert D'Haens (Conceptualization: Equal; Supervision: Equal; Writing – review & editing: Supporting), David Laharie (Conceptualization: Equal; Supervision: Equal; Writing – review & editing: Supporting), Laurent Peyrin-Biroulet (Conceptualization: Equal; Investigation: Equal; Methodology: Equal; Supervision: Equal; Validation: Equal; Writing – review & editing: Equal), Séverine Vermeire (Conceptualization: Equal; Investigation: Equal; Methodology: Equal; Supervision: Equal; Validation: Equal; Writing – review & editing: Lead) Conflicts of interest These authors disclose the following: PB has received financial support for research from AbbVie, Mundipharma, Pfizer, Janssen, and Mylan; lecture fees from AbbVie, Takeda, Pfizer, and Janssen; and advisory board fees from AbbVie, BMS, Takeda, Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer, Sandoz, and Pentax. ED is a postdoctoral research fellow of the Research Foundation – Flanders (FWO), Belgium (grant number 12X9420N) and received consultancy fees from Janssen (all honoraria/fees paid to the department). MZ has received lecture fees from AbbVie. FB has received lectures and consultancy fees from AbbVie, Amgen Chiesi, Ipsen, MSD, and Roche; and consultancy fees from AbbVie, Celgene, Falk, Ferring, Janssen, Mundipharma, MSD, Norgine Pfizer, Takeda, and Vifor. GD has served as advisor for AbbVie, Ablynx, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Applied Molecular Therapeutics, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, DSM Pharma, Echo Pharmaceuticals, Eli Lilly, Engene, Exeliom Biosciences, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Kintai Therapeutics, Lycera, Medimetrics, Millenium/Takeda, Medtronics, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, ProciseDx, Prodigest, Prometheus Laboratories/Nestle, Progenity, Protagonist, RedHill, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; and received speaker fees from AbbVie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor. DL has received advisory board or lectures fees from AbbVie, Celgene, Ferring, Janssen, MSD, Novartis, Pfizer, Roche, and Takeda. LPB has received personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen; grants from AbbVie, MSD, and Takeda; and stock options from CTMA. SV has received financial support for research from MSD, AbbVie, Takeda, Pfizer, J & J; lecture fee(s) from MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, and Genentech/Roche; and consultancy fees from MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche, Celgene, Mundipharma, Celltrion, SecondGenome, Prometheus, Shire, Prodigest, Gilead, Galapagos, and MRM Health. The remaining authors disclose no conflicts. Funding Information: Conflicts of interest These authors disclose the following: PB has received financial support for research from AbbVie, Mundipharma, Pfizer, Janssen, and Mylan; lecture fees from AbbVie, Takeda, Pfizer, and Janssen; and advisory board fees from AbbVie, BMS, Takeda, Hospira, Janssen, MSD, Mundipharma, Roche, Pfizer, Sandoz, and Pentax. ED is a postdoctoral research fellow of the Research Foundation – Flanders (FWO), Belgium (grant number 12X9420N) and received consultancy fees from Janssen (all honoraria/fees paid to the department). MZ has received lecture fees from AbbVie. FB has received lectures and consultancy fees from AbbVie, Amgen Chiesi, Ipsen, MSD, and Roche; and consultancy fees from AbbVie, Celgene, Falk, Ferring, Janssen, Mundipharma, MSD, Norgine Pfizer, Takeda, and Vifor. GD has served as advisor for AbbVie, Ablynx, Allergan, Alphabiomics, Amakem, Amgen, AM Pharma, Applied Molecular Therapeutics, Arena Pharmaceuticals, AstraZeneca, Avaxia, Biogen, Bristol Meiers Squibb, Boehringer Ingelheim, Celgene/Receptos, Celltrion, Cosmo, DSM Pharma, Echo Pharmaceuticals, Eli Lilly, Engene, Exeliom Biosciences, Ferring, DrFALK Pharma, Galapagos, Genentech/Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Hospira/Pfizer, Immunic, Johnson and Johnson, Kintai Therapeutics, Lycera, Medimetrics, Millenium/Takeda, Medtronics, Mitsubishi Pharma, Merck Sharp Dome, Mundipharma, Nextbiotics, Novonordisk, Otsuka, Pfizer/Hospira, Photopill, ProciseDx, Prodigest, Prometheus Laboratories/Nestle, Progenity, Protagonist, RedHill, Robarts Clinical Trials, Salix, Samsung Bioepis, Sandoz, Seres/Nestle, Setpoint, Shire, Teva, Tigenix, Tillotts, Topivert, Versant, and Vifor; and received speaker fees from AbbVie, Biogen, Ferring, Johnson and Johnson, Merck Sharp Dome, Mundipharma, Norgine, Pfizer, Samsung Bioepis, Shire, Millenium/Takeda, Tillotts, and Vifor. DL has received advisory board or lectures fees from AbbVie, Celgene, Ferring, Janssen, MSD, Novartis, Pfizer, Roche, and Takeda. LPB has received personal fees from AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen; grants from AbbVie, MSD, and Takeda; and stock options from CTMA. SV has received financial support for research from MSD, AbbVie, Takeda, Pfizer, J&J; lecture fee(s) from MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, and Genentech/Roche; and consultancy fees from MSD, AbbVie, Takeda, Ferring, Centocor, Hospira, Pfizer, J&J, Genentech/Roche, Celgene, Mundipharma, Celltrion, SecondGenome, Prometheus, Shire, Prodigest, Gilead, Galapagos, and MRM Health. The remaining authors disclose no conflicts. Publisher Copyright: © 2021 AGA Institute
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