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Article ; Online: Reply.

Petitcollin, Antoine / Bouguen, Guillaume

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2020 Volume 19, Issue 11, Page(s) 2458–2459

Language	English
Publishing date	2020-11-26
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2020.07.001
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Article: A Reproducible and Individualized Method to Predict Osmolality of Compounded Pediatric Parenteral Nutrition Solutions.

Petitcollin, Antoine / Duval, Stéphanie / Bouissou, Antoine / Bourgoin, Hélène

JPEN. Journal of parenteral and enteral nutrition

2016 Volume 40, Issue 7, Page(s) 1021–1032

Abstract: Background: Osmolality is a well-known factor in complications associated with parenteral nutrition (PN). The osmolality of compounded pediatric PN solutions is often inappropriately approximated by theoretical osmolarity, which carries a major risk of ... ...

Abstract	Background: Osmolality is a well-known factor in complications associated with parenteral nutrition (PN). The osmolality of compounded pediatric PN solutions is often inappropriately approximated by theoretical osmolarity, which carries a major risk of underestimation, especially in highly concentrated solutions. Only a few studies have proposed equations to overcome this problem, and to date their accuracy in settings other than those of their development has not been assessed. We propose a reproducible method to develop a predictive model of osmolality adapted to local practice, and we compare its predictive performance to osmolarity calculation and other equations. Methods: From measures performed on dilutions of basic components of PN solutions, a predictive model establishing the relationship between the quantitative and qualitative composition of a PN solution and its osmolality was developed. This model was validated in routine practice on daily compounded pediatric PN solutions, and its predictive performance was compared with osmolarity calculation, 2 previously published predictive equations, and multilinear regression. Results: We measured the osmolality of 321 routinely produced PN solutions. The model predicted osmolality with a mean relative error of -0.28% (±2.75%). All the other ways to approximate osmolality were less precise and sometimes provided critically underestimated values (from -16.67% to -33.24%). Conclusions: Our model predicted osmolality accurately and may be used in routine practice in any setting once adapted to the local production practice. Approximations by osmolarity severely underestimate actual osmolality. Keeping osmolarity <800 mOsm/L seems sufficient to ensure that actual osmolality does not exceed 1000 mOsm/kg.
Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	800861-9
ISSN	0148-6071
ISSN	0148-6071
DOI	10.1177/0148607115570695
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Article ; Online: Pharmacogenetics of Membrane Transporters of Tacrolimus in Solid Organ Transplantation.

Tron, Camille / Lemaitre, Florian / Verstuyft, Céline / Petitcollin, Antoine / Verdier, Marie-Clémence / Bellissant, Eric

Clinical pharmacokinetics

2018 Volume 58, Issue 5, Page(s) 593–613

Abstract: Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide interpatient variability in terms of its pharmacokinetics that may in part be due ...

Abstract	Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide interpatient variability in terms of its pharmacokinetics that may in part be due to genetic factors. The pharmacogenetics of drug transporters is therefore a promising area to explore in the clinical pharmacology of tacrolimus. The aim of this review is to provide an overview of currently available data regarding the pharmacogenetics of membrane transporters that may be involved in the interindividual variability of the response to tacrolimus. Several genetic variants in genes coding for influx or efflux membrane transporters (e.g. ABCB1, ABCC2, ABCC8, SLC30A8, SLCO1B1/3, SLC28A1, SLC22A11, and SLC28A3) have been associated with tacrolimus pharmacokinetics variability or the occurrence of toxicity; however, there is still a degree of controversy as to the impact of these variants in vivo and further investigations are needed to confirm these results in larger cohorts and to validate the relevance of such genetic biomarkers for personalization of immunosuppressive therapy in solid organ transplantations. The relationship between transporter polymorphisms and the intracellular concentration of tacrolimus should also be further investigated. Finally, the main challenge could be elucidation of the interplay of biological mechanisms underlying genetic variations that alter the drug concentration or its clinical effect.
MeSH term(s)	Animals ; Humans ; Immunosuppressive Agents/pharmacokinetics ; Immunosuppressive Agents/pharmacology ; Membrane Transport Proteins/genetics ; Membrane Transport Proteins/metabolism ; Organ Transplantation ; Polymorphism, Single Nucleotide ; Tacrolimus/pharmacokinetics ; Tacrolimus/pharmacology
Chemical Substances	Immunosuppressive Agents ; Membrane Transport Proteins ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2018-11-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-018-0717-7
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Article ; Online: Pharmacokinetic Parameters of Infliximab Influence the Rate of Relapse After De-Escalation in Adults With Inflammatory Bowel Diseases.

Petitcollin, Antoine / Brochard, Charlène / Siproudhis, Laurent / Tron, Camille / Verdier, Marie-Clémence / Lemaitre, Florian / Lucidarme, Camille / Bouguen, Guillaume / Bellissant, Éric

Clinical pharmacology and therapeutics

2019 Volume 106, Issue 3, Page(s) 605–615

Abstract: This study aimed at exploring the link among individual concentrations, pharmacokinetic parameters, and the probability of relapse after de-escalation in a real-world prospective cohort of patients with inflammatory bowel disease (IBD) who underwent ... ...

Abstract	This study aimed at exploring the link among individual concentrations, pharmacokinetic parameters, and the probability of relapse after de-escalation in a real-world prospective cohort of patients with inflammatory bowel disease (IBD) who underwent infliximab treatment de-escalation. Ninety-one patients were included. A time-varying compartment model was used to estimate individual pharmacokinetic parameters and trough concentrations. A Cox model was implemented to explore the parameters influencing the probability of relapse after de-escalation. Volume, clearance, and trough before and after de-escalation were linked to the relapse risk at the univariate step. Independent predictors of relapse were tobacco use and/or ulcerative colitis (P = 0.0093), a higher C-reactive protein (CRP; P = 0.00064), and an infliximab trough < 2.4 μg/mL after de-escalation (P = 0.0001). Patients with trough > 5.7 μg/mL are eligible to de-escalation, but infliximab pharmacokinetics is highly variable in time. Therefore, drug monitoring is mandatory after de-escalation to maintain trough > 2.4 μg/mL. Clearance monitoring seems an appealing approach for patient selection and relapse prediction.
MeSH term(s)	Adult ; C-Reactive Protein ; Colitis, Ulcerative/drug therapy ; Female ; Gastrointestinal Agents/pharmacokinetics ; Gastrointestinal Agents/therapeutic use ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/epidemiology ; Infliximab/pharmacokinetics ; Infliximab/therapeutic use ; Male ; Metabolic Clearance Rate ; Middle Aged ; Proportional Hazards Models ; Recurrence ; Remission Induction ; Time Factors ; Tobacco Use/epidemiology
Chemical Substances	Gastrointestinal Agents ; C-Reactive Protein (9007-41-4) ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2019-04-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.1429
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Article ; Online: Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infections: The Fluo-pop study.

Lemaitre, Florian / Fily, Fabien / Foulquier, Jean-Baptiste / Revest, Matthieu / Jullien, Vincent / Petitcollin, Antoine / Tattevin, Pierre / Tron, Camille / Polard, Jean-Louis / Verdier, Marie-Clémence / Comets, Emmanuelle / Huten, Denis / Arvieux, Cédric / Bellissant, Eric / Laviolle, Bruno

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2021 Volume 142, Page(s) 112053

Abstract: Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular ... ...

Abstract	Fluoroquinolones efficacy depend on both the drug exposure and the level of drug resistance of the bacteria responsible for the infection. Specifically for the Staphylococcus species, which is the microorganism mainly involved in osteoarticular infections (OAI), in-vitro data reported that an AUC/MIC ratio above 115 h maximizes drug efficacy. However, data on OAI patients are lacking and a simple approach to access AUCs is still a clinical issue. We conducted a prospective, single-center study in 30 OAI patients hospitalized in the Rennes University Hospital to model ofloxacin pharmacokinetics and to define a limited sampling strategy (LSS) suitable for ofloxacin and levofloxacin treatments. Modeling was conducted with the Monolix software. The final model was externally validated using levofloxacin data. Monte-Carlo simulations were used to evaluate the probability of target attainment (PTA) of different dosing regimens. Two hundred and ninety-seven (297) ofloxacin concentrations were available for the pharmacokinetic modeling. Ofloxacin pharmacokinetics was best described using a bicompartmental model with a first order elimination, and a transit compartment model absorption. CKD-EPI and sex explained half of ofloxacin pharmacokinetic variability. For LSS, the 0, 1 h and 3 h sampling scheme resulted in the best approach both for BID and TID dosages (R
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage ; Anti-Bacterial Agents/blood ; Anti-Bacterial Agents/pharmacokinetics ; Bone Diseases, Infectious/drug therapy ; Female ; Fluoroquinolones/administration & dosage ; Fluoroquinolones/blood ; Fluoroquinolones/pharmacokinetics ; Humans ; Joint Diseases/drug therapy ; Levofloxacin/administration & dosage ; Levofloxacin/blood ; Levofloxacin/pharmacokinetics ; Male ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Ofloxacin/administration & dosage ; Ofloxacin/blood ; Ofloxacin/pharmacokinetics ; Prospective Studies ; Staphylococcus/drug effects ; Young Adult
Chemical Substances	Anti-Bacterial Agents ; Fluoroquinolones ; Levofloxacin (6GNT3Y5LMF) ; Ofloxacin (A4P49JAZ9H)
Language	English
Publishing date	2021-08-19
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2021.112053
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Article ; Online: Modelling of the Time-Varying Pharmacokinetics of Therapeutic Monoclonal Antibodies: A Literature Review.

Petitcollin, Antoine / Bensalem, Amina / Verdier, Marie-Clémence / Tron, Camille / Lemaitre, Florian / Paintaud, Gilles / Bellissant, Eric / Ternant, David

Clinical pharmacokinetics

2019 Volume 59, Issue 1, Page(s) 37–49

Abstract: Therapeutic monoclonal antibodies (mAbs) are increasingly used to treat a variety of conditions. The sources of their interindividual pharmacokinetic (PK) variability have been extensively studied, but few data on their intraindividual PK variability are ...

Abstract	Therapeutic monoclonal antibodies (mAbs) are increasingly used to treat a variety of conditions. The sources of their interindividual pharmacokinetic (PK) variability have been extensively studied, but few data on their intraindividual PK variability are available. In this article, we reviewed the published population compartmental models used to describe the time-varying PK of mAbs in clinical settings. Of 189 publications, 13 report the use of time-varying parameters and 30 describe the effects of antidrug antibody (ADA) development. Currently published time-varying models mainly describe fast decreases in clearance due to target-mediated elimination or slow decreases in clearance owing to cachexia reduction. Immunogenicity models mostly describe 'on-off' increases of clearance due to a rapid elimination of mAbs-ADA complexes. Some more sophisticated models attempted to decipher the time course of immunogenic response, notably by accounting for the time of onset and progressive increase in ADA production. Currently available time-varying and immunogenicity models are empirical approximations of the complex mAb disposition, but they emphasize the necessity to account for the temporal variations of mAb PK in model building. The clinical implications of the time-varying PK of mAbs are not fully understood, but some publications reported a link between clearance decrease and disease improvement. The future perspectives offered by this knowledge include the possibility to adapt the regimen to the disease and the patients' state, and also to immune status, and to monitor their evolution by monitoring PK variations.
MeSH term(s)	Algorithms ; Antibodies, Monoclonal/pharmacokinetics ; Antibodies, Monoclonal/therapeutic use ; Biological Variation, Population ; Cachexia/chemically induced ; Cachexia/epidemiology ; Cachexia/prevention & control ; Dose-Response Relationship, Immunologic ; Humans ; Immunologic Factors/pharmacokinetics ; Immunologic Factors/therapeutic use ; Metabolic Clearance Rate/physiology ; Models, Biological ; Time Factors
Chemical Substances	Antibodies, Monoclonal ; Immunologic Factors
Language	English
Publishing date	2019-08-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	197627-8
ISSN	1179-1926 ; 0312-5963
ISSN (online)	1179-1926
ISSN	0312-5963
DOI	10.1007/s40262-019-00816-7
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Article ; Online: Tacrolimus overexposure in kidney transplant recipients during the first post-operative week: caution is required in older patients.

Lemaitre, Florian / Lorcy, Nolwen / Tron, Camille / Golbin, Léonard / Petitcollin, Antoine / Verdier, Marie-Clémence / Vigneau, Cécile / Bellissant, Eric

Fundamental & clinical pharmacology

2018 Volume 33, Issue 3, Page(s) 347–354

Abstract: In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus ... ...

Abstract	In liver transplantation, tacrolimus trough concentrations (Cmin) above 20 ng/mL during the first days led to worse outcome at 1 year but data in the kidney transplant (KT) era are scarce. The aim of this study was to evaluate the impact of tacrolimus overexposure during the first week post-transplantation on the kidney function (KF) of KT recipients. In this retrospective study, 105 KT recipients were attributed to overexposure group (OG) or normal group according to their Cmin during the first week of treatment. KF was evaluated by comparing the rate of delayed graft function (DGF) and by collecting plasma creatinine from day 1, 2, 3, 4, 5, 6, 7, 14, 21, 28 and at 1 year. Risk factors for developing DGF were also investigated using a multivariate model. DGF was more frequent in OG (43% of patients; P = 0.027) which has higher plasma creatinine on day 7, 14, and 21. OG patients were older with more extended criteria donor's grafts. In the multivariate analysis, only cold ischemia time (CIT) remained associated with DGF (OR = 1.003), while TAC overexposure did not reach significance (P = 0.06; OR = 3.9). In this study, we confirmed the predominant role of CIT as a risk factor for the onset of DGF in kidney transplantation. 43% of KT recipients were overexposed with more DGF, especially older patients.
MeSH term(s)	Adult ; Age Factors ; Aged ; Cold Ischemia/statistics & numerical data ; Creatinine/blood ; Delayed Graft Function/epidemiology ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/pharmacokinetics ; Kidney Transplantation/methods ; Middle Aged ; Multivariate Analysis ; Retrospective Studies ; Risk Factors ; Tacrolimus/administration & dosage ; Tacrolimus/pharmacokinetics ; Time Factors
Chemical Substances	Immunosuppressive Agents ; Creatinine (AYI8EX34EU) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2018-12-07
Publishing country	England
Document type	Journal Article
ZDB-ID	639134-5
ISSN	1472-8206 ; 0767-3981
ISSN (online)	1472-8206
ISSN	0767-3981
DOI	10.1111/fcp.12432
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Article ; Online: Predictors of relapse following infliximab de-escalation in patients with inflammatory bowel disease: the value of a strategy based on therapeutic drug monitoring.

Lucidarme, Camille / Petitcollin, Antoine / Brochard, Charlène / Siproudhis, Laurent / Dewitte, Marie / Landemaine, Amandine / Bellissant, Eric / Bouguen, Guillaume

Alimentary pharmacology & therapeutics

2018 Volume 49, Issue 2, Page(s) 147–154

Abstract: Background: There are limited data concerning infliximab drug monitoring during de-escalation of the treatment of inflammatory bowel disease (IBD).: Aim: To define the rate and the predictors of relapse following infliximab de-escalation in IBD ... ...

Abstract	Background: There are limited data concerning infliximab drug monitoring during de-escalation of the treatment of inflammatory bowel disease (IBD). Aim: To define the rate and the predictors of relapse following infliximab de-escalation in IBD patients in remission. Methods: All IBD patients at a single referral centre in clinical and biological remission and in whom the dose of infliximab had been de-escalated were included. Patients in remission with a high trough level of infliximab (>7 mg/L) were considered to be trough level-based de-escalation patients. The data were retrieved from a prospective IBD database. Actuarial analysis was performed for statistical purposes. Results: A total of 146 de-escalations were performed in 96 patients (Crohn's disease/ulcerative colitis: 68%/32%); 54 (37%) were based on clinical remission only, and 92 (63%) were based on clinical remission associated with a trough level above 7 mg/L. The cumulative probabilities of relapse following infliximab de-escalation were 16% and 47% at 1 and 2 years, respectively. Ulcerative colitis was associated with an increased risk of relapse (HR = 3.2, P = 0.005). Conversely, combination therapy at infliximab initiation (HR = 0.39, P = 0.0110) and trough level-based de-escalation were associated with decreased risk of relapse (HR = 0.45, P = 0.024). Trough levels before and after de-escalation were well correlated; a decrease by half was observed following a 2-week interval increase or a half-dose decrease. Conclusion: The use of trough levels to assess the feasibility of dose de-escalation seems to be a prerequisite for decreasing the risk of relapse.
MeSH term(s)	Adult ; Colitis, Ulcerative/blood ; Colitis, Ulcerative/diagnosis ; Colitis, Ulcerative/drug therapy ; Crohn Disease/blood ; Crohn Disease/diagnosis ; Crohn Disease/drug therapy ; Drug Monitoring/methods ; Drug Monitoring/trends ; Drug Therapy, Combination ; Female ; Gastrointestinal Agents/administration & dosage ; Gastrointestinal Agents/blood ; Humans ; Inflammatory Bowel Diseases/blood ; Inflammatory Bowel Diseases/diagnosis ; Inflammatory Bowel Diseases/drug therapy ; Infliximab/administration & dosage ; Infliximab/blood ; Male ; Middle Aged ; Predictive Value of Tests ; Prospective Studies ; Recurrence ; Remission Induction/methods ; Withholding Treatment/trends
Chemical Substances	Gastrointestinal Agents ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2018-12-27
Publishing country	England
Document type	Journal Article
ZDB-ID	639012-2
ISSN	1365-2036 ; 0269-2813 ; 0953-0673
ISSN (online)	1365-2036
ISSN	0269-2813 ; 0953-0673
DOI	10.1111/apt.15046
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Article ; Online: Pharmacogenetic-Whole blood and intracellular pharmacokinetic-Pharmacodynamic (PG-PK2-PD) relationship of tacrolimus in liver transplant recipients.

Tron, Camille / Woillard, Jean-Baptiste / Houssel-Debry, Pauline / David, Véronique / Jezequel, Caroline / Rayar, Michel / Balakirouchenane, David / Blanchet, Benoit / Debord, Jean / Petitcollin, Antoine / Roussel, Mickaël / Verdier, Marie-Clémence / Bellissant, Eric / Lemaitre, Florian

PloS one

2020 Volume 15, Issue 3, Page(s) e0230195

Abstract: Tacrolimus (TAC) is the cornerstone of immunosuppressive therapy in liver transplantation. This study aimed at elucidating the interplay between pharmacogenetic determinants of TAC whole blood and intracellular exposures as well as the pharmacokinetic- ... ...

Abstract	Tacrolimus (TAC) is the cornerstone of immunosuppressive therapy in liver transplantation. This study aimed at elucidating the interplay between pharmacogenetic determinants of TAC whole blood and intracellular exposures as well as the pharmacokinetic-pharmacodynamic relationship of TAC in both compartments. Complete pharmacokinetic profiles (Predose, and 20 min, 40 min, 1h, 2h, 3h, 4h, 6h, 8h, 12h post drug intake) of twice daily TAC in whole blood and peripheral blood mononuclear cells (PBMC) were collected in 32 liver transplanted patients in the first ten days post transplantation. A non-parametric population pharmacokinetic model was applied to explore TAC pharmacokinetics in blood and PBMC. Concurrently, calcineurin activity was measured in PBMC. Influence of donor and recipient genetic polymorphisms of ABCB1, CYP3A4 and CYP3A5 on TAC exposure was assessed. Recipient ABCB1 polymorphisms 1199G>A could influence TAC whole blood and intracellular exposure (p<0.05). No association was found between CYP3A4 or CYP3A5 genotypes and TAC whole blood or intracellular concentrations. Finally, intra-PBMC calcineurin activity appeared incompletely inhibited by TAC and less than 50% of patients were expected to achieve intracellular IC50 concentration (100 pg/millions of cells) at therapeutic whole blood concentration (i.e.: 4-10 ng/mL). Together, these data suggest that personalized medicine regarding TAC therapy might be optimized by ABCB1 pharmacogenetic biomarkers and by monitoring intracellular concentration whereas the relationship between intracellular TAC exposure and pharmacodynamics biomarkers more specific than calcineurin activity should be further investigated.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/genetics ; Aged ; Cytochrome P-450 CYP3A/genetics ; Female ; Genotype ; Humans ; Immunosuppression/methods ; Immunosuppressive Agents/pharmacokinetics ; Immunosuppressive Agents/therapeutic use ; Leukocytes, Mononuclear/metabolism ; Liver Transplantation/methods ; Male ; Middle Aged ; Pharmacogenetics/methods ; Pharmacogenomic Testing/methods ; Polymorphism, Single Nucleotide/genetics ; Tacrolimus/pharmacokinetics ; Tacrolimus/therapeutic use
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B ; Immunosuppressive Agents ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2020-03-12
Publishing country	United States
Document type	Journal Article
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0230195
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Article ; Online: Cumulative Exposure to Infliximab, But Not Trough Concentrations, Correlates With Rate of Infection.

Landemaine, Amandine / Petitcollin, Antoine / Brochard, Charlène / Miard, Céline / Dewitte, Marie / Le Balc'h, Eric / Grainville, Thomas / Bellissant, Eric / Siproudhis, Laurent / Bouguen, Guillaume

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association

2020 Volume 19, Issue 2, Page(s) 288–295.e4

Abstract: Background & aims: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with ... ...

Abstract	Background & aims: Infliximab increases the risk of infection in patients with inflammatory bowel diseases (IBD), but there is controversy over the relationship between drug concentration and infections. We aimed to assess factors associated with infection in infliximab-treated patients, including pharmacokinetic features. Methods: We collected data from 209 patients with IBD (102 men; mean age, 39 y; 159 with Crohn's disease; 54 received combination therapy) who received an infliximab maintenance regimen from November 2016 through April 2017 in France. Data were collected from each infusion visit (total of 640 infusions). Infliximab exposure was estimated based on the area under the curve (AUC) of drug concentration in pharmacokinetic models; individual exposures over the 6-month period were estimated based on the sum of the AUC (ΣAUC). Results: The mean infliximab trough level was 5.46 mg/L, and the mean ΣAUC was 3938 ± 1427 mg.d/L. A total of 215 infections were collected from the 640 infusion visits; 123 patients (59%) had at least 1 infection. Factors independently associated with infection after multivariate analysis were smoking (odds ratio [OR], 2.05; P = .046), IBD flare (OR, 2.71; P = .006), and a high ΣAUC of infliximab (above 3234 mg x d/L) (OR, 2.02; P = .02). The ΣAUC was higher in patients with an occurrence of infection (P = .04) and correlated with the number of infections (P = .04). Trough concentration of infliximab alone was not associated with infection. Conclusions: Almost two-thirds of patients treated with infliximab developed an infection; risk was individually correlated with cumulative increase in drug exposure, but not infliximab trough level.
MeSH term(s)	Adult ; Area Under Curve ; Crohn Disease/drug therapy ; France ; Gastrointestinal Agents/adverse effects ; Humans ; Inflammatory Bowel Diseases/drug therapy ; Infliximab/adverse effects ; Male
Chemical Substances	Gastrointestinal Agents ; Infliximab (B72HH48FLU)
Language	English
Publishing date	2020-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2119789-1
ISSN	1542-7714 ; 1542-3565
ISSN (online)	1542-7714
ISSN	1542-3565
DOI	10.1016/j.cgh.2020.03.018
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