Patient Factors That Increase Infliximab Clearance and Shorten Half-life in Inflammatory Bowel Disease

Dotan, Iris; Ron, Yulia; Yanai, Henit; Becker, S.J.; Fishman, Sigal; Yahav, Lior; Yehoyada, Merav Ben; Mould, Diane R.

doi:10.1097/mib.0000000000000212

Cited by 244 publications

(181 citation statements)

References 57 publications

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“…27 Since only trough concentrations were available, we used a one-compartment model. Because most studies used a 2-compartmental model to describe infliximab pharmacokinetics, [4][5][6][8][9][10]12,13 there is a potential risk of increased bias and decreased precision of PK parameter estimation. However, this limitation was reported for compounds with poorly known pharmacokinetics, which is not the case of infliximab.…”

Section: Discussionmentioning

confidence: 99%

“…Despite the adjustment of dose based on patients' weight, large interindividual variability in infliximab serum concentrations is observed. [1][2][3] Infliximab pharmacokinetics has been analyzed in RA, 4 AS 5,6 and inflammatory bowel disease (IBD) [7][8][9][10][11][12] patients using population compartmental modeling. These studies showed that several individual characteristics such as body weight, [4][5][6]9,10,12,13 sex, 5,9,13 anti-drug antibodies, 14,15 cotreatment with methotrexate 4 or preinfusion C-reactive protein (CRP) 4 were related to infliximab pharmacokinetic parameters.…”

Section: Introductionmentioning

confidence: 99%

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The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Passot

Mulleman

Bejan-Angoulvant

et al. 2016

mAbs

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Infliximab is an anti-tumor necrosis factor monoclonal antibody approved in chronic inflammatory diseases such as rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD) and ulcerative colitis (UC). Infliximab pharmacokinetics is variable between patients, but influence of the underlying disease was never assessed. This study aimed at assessing this influence using a cohort of patients monitored in a single center and with the same assay. Infliximab trough concentrations were determined on samples collected between weeks 0 and 22 after treatment initiation in 218 patients treated for RA, PsA, AS, CD or UC. Infliximab pharmacokinetics was analyzed by a onecompartment population model with first-order elimination rate constant. In AS patients, volume of distribution (V) and elimination clearance (CL) were 5.4 L and 0.24 L/day, respectively. In CD and UC patients, V was 49% and 52% higher than in AS, respectively, and CL was 47% and 60% higher than in AS, respectively. In RA patients, CL was 49% higher than in AS patients. Simulations showed that without methotrexate, a 3 mg/kg dosing regimen would lead only 16% of RA patients to reach the target concentration (2.5 mg/L) at week 22, whereas target concentrations would be reached in approximately half of RA patients cotreated with methotrexate, as well as half of CD (3.5 mg/L) and UC (3.7 mg/L) patients. The suboptimality of approved dosing regimens supports the development of dosing optimization based on concentration measurements.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Passot

Mulleman

Bejan-Angoulvant

et al. 2016

mAbs

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“…Aunque mayores dosis sean utilizadas, un clearance aumentado del fármaco afectará los niveles hacia el final de cada intervalo 23,24 . En nuestra paciente decidimos utilizar un esquema acelerado (0, 1 y 4 semanas) con aumento de la dosis administrada (10 mg/kg) dado la severidad clínica y endoscópica 12 .…”

Section: Discussionunclassified

Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides. Caso clínico

et al. 2017

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“…In addition to low serum albumin and high body weight, the presence of antitherapy antibodies was also a patient factor signifi cantly associated with high infl iximab clearance; antitherapy antibody formation was associated with a 259% increase in infl iximab clearance ( 59 ).…”

Section: Antidrug Antibodymentioning

confidence: 99%

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

Lichtenstein¹,

McGovern²

2016

Am J Gastroenterol Suppl

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Biomarkers, radiology fi ndings, and endoscopic studies, together with clinical assessment of patients with infl ammatory bowel disease, can be used to help determine prognosis, assess disease activity, and increasingly to inform treatment decision-making. This article reviews the current "state of the science" regarding the multitude of different tests that can be performed and how these can be used in the clinic to guide management. Initially, when patients present with symptoms suggestive of infl ammatory bowel disease (IBD), standard endoscopic studies and radiographic studies should be performed and the use of combinations of serologic and fecal markers may additionally be incorporated into patient assessment. Once the patient has a formal diagnosis, prognosis should be assessed and serologic evaluation may be used, but in conjunction with endoscopic and radiographic studies. Within the context of evaluating clinical predictors of disease (e.g., disease location, nutritional status, routine blood tests), early mucosal healing has been linked to better outcomes, and failure to heal the mucosa has been associated with poorer outcomes. Evaluation of response to therapy can be approximated with the use of biomarkers (e.g., C-reactive protein, fecal calprotectin, lactoferrin), and therapeutic drug monitoring has enabled us to assess levels of drug metabolites, drug levels, and antidrug antibodies to guide the ongoing management. Although there is not yet universal adoption of biomarkers to determine treatment choices (e.g., the use of anti-tumor necrosis factor therapy), biomarkers have enabled us to "fi ne tune" treatment of some patients with IBD. Establishing mechanisms of communicating these risks/benefi ts to patients will be a considerable challenge and remains a priority area of research.

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Patient Factors That Increase Infliximab Clearance and Shorten Half-life in Inflammatory Bowel Disease

Cited by 244 publications

References 57 publications

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

The underlying inflammatory chronic disease influences infliximab pharmacokinetics

Terapia de inducción acelerada con infliximab en paciente con colitis ulcerosa grave refractaria a corticoides. Caso clínico

Using Markers in IBD to Predict Disease and Treatment Outcomes: Rationale and a Review of Current Status

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