Serum Adalimumab Concentration and Clinical Remission in Patients with Crohnʼs Disease

Chiu, Yi‐Lin; Rubin, David T.; Vermeire, Séverine; Louis, Édouard; Robinson, Anne; Lomax, Kathleen G.; Pollack, Paul; Paulson, Susan K.

doi:10.1097/mib.0b013e3182813242

Cited by 115 publications

(82 citation statements)

References 28 publications

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“…It has been demonstrated that co-administration of azathioprine with adalimumab had little to no impact on adalimumab clearance. 32,33 In contrast to this the SONIC trial demonstrated that the combination of azathioprine and infliximab increased infliximab trough concentrations by more than 2-fold as compared to infliximab alone. 14 In the rheumatoid arthritis literature concomitant use of IM clearly influences ADA levels, trough levels and clinical response to both infliximab and adalimumab.…”

Section: Discussionmentioning

confidence: 95%

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

Jones

Kaplan

Peyrin–Biroulet

et al. 2015

Clinical Gastroenterology and Hepatology

111

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Section: Discussionmentioning

confidence: 95%

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

Jones

Kaplan

Peyrin–Biroulet

et al. 2015

Clinical Gastroenterology and Hepatology

111

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“…For this description, we first used CRP as a biomarker. Indeed, CRP has been shown repeatedly to correlate well with sustained clinical response [8,17,18,20], and the relationship between infliximab concentration and CRP was previously investigated in RA [32,33]. Being an anti-TNF-α monoclonal antibody, adalimumab acts as a noncompetitive antagonist of TNF-α and does not act directly on CRP.…”

Section: Figurementioning

confidence: 99%

“…Given that normalization of CRP is associated with sustained clinical response, CRP may be considered as a clinically relevant biomarker [13,[17][18][19][20]. In addition, CRP is increased by TNF-α [21].…”

Section: Structural Modelsmentioning

confidence: 99%

Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

Ternant

Ducourau

Fuzibet

et al. 2015

Brit J Clinical Pharma

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AIMSThis study aimed at describing adalimumab pharmacokinetics (PK) and the concentration-effect relationship of adalimumab using pharmacokineticpharmacodynamic (PK-PD) modelling in patients with rheumatoid arthritis (RA). METHODSAdalimumab PK and PK-PD data were obtained from a multicentric observational study. Adalimumab (40 mg) was administered subcutaneously every other week, and its pharmacokinetics was described using a one-compartment model. The relationship between adalimumab concentration and C-reactive protein (CRP) concentration was described using an indirect response model with inhibition of CRP input, whereas the relationship between adalimumab concentration and disease activity score in 28 joints (DAS28) was described using a direct inhibition model. Dose regimens that included a loading dose of adalimumab were simulated. RESULTSThirty patients treated for RA were analysed. The following pharmacokinetic and PK-PD parameters were estimated (interidividual coefficient of variation): apparent volume of distribution (Vd/F) = 10.8 l (92%); apparent clearance (CL/F) = 0.32 l day −1 (17%); first-order absorption rate (ka) = 0.28 day; CRP input (kin) = 22.0 mg l −1 day −1 (65%); adalimumab concentration leading to a 50% decrease in kin (C50) = 3.6 mg l −1 (88%); baseline DAS28 (DAS0) = 5.5 mg l −1 (11%); and adalimumab concentration leading to 50% decrease of DAS0 (IC50) = 11.0 mg l −1 (71%). Simulations showed that a 160 mg loading dose should reduce the time to reach efficacy in terms of both CRP and DAS28 after the first injection.

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“…Consensus is increasing that trough levels of both anti-TNFa and ADA should be monitored in patients who have undergone anti-TNFa therapy. A few clinical investigators have studied the relationship between anti-TNFa and ADA values in clinical response, disease activity, prognosis, and treatment strategy management [40][41][42][43][44].…”

Section: Biomarkers Predicting Therapeutic Efficacymentioning

confidence: 99%

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

Jiang

2015

Mol Diagn Ther

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Biomarkers of inflammatory bowel disease (IBD) are non-invasive or minimally invasive tests for IBD diagnosis and/or prognosis as well as assessment of disease activity and response to therapy. Here, we update the current status of IBD biomarkers, including serological, fecal, and genetic (DNA and microRNA [miRNA]) biomarkers. As an update, the classical serological biomarkers, including ASCA, pANCA, anti-OmpC, anti-Cbir, anti-I2, and other anti-glycan antibodies, are discussed only briefly. Emphasis in this article is given to those that have been recently identified or extensively characterized, as well as to the clinical utilities of biomarkers, with special attention to prediction of disease complication and activity assessment, mucosal healing, and response to therapies. In particular, we discuss the utilities of blood-based biomarkers predicting therapeutic response to anti-tumor necrosis factor (TNF)-α, such as anti-anti-TNFα antibodies or anti-drug antibodies (ADA) and trough level of anti-TNFα. Fecal biomarkers, which have recently attracted substantial attention, are also discussed extensively, including the well-characterized calprotectin and lactoferrin, as well as the recently characterized M2-PK, CHI3L1, neopterin, MMP-9, and HMGB1. Genome and exome sequencing enables the discovery of a number of rare yet disease-defining IBD-susceptible genes, particularly those involved in very early onset IBD, providing rare yet extremely useful biomarkers at genetic levels for IBD diagnosis/prognosis. Finally, we briefly summarize the discovery, characterization, and potential implications of miRNA as potential IBD biomarkers.

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Serum Adalimumab Concentration and Clinical Remission in Patients with Crohnʼs Disease

Cited by 115 publications

References 28 publications

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

Effects of Concomitant Immunomodulator Therapy on Efficacy and Safety of Anti–Tumor Necrosis Factor Therapy for Crohn’s Disease: A Meta-analysis of Placebo-controlled Trials

Pharmacokinetics and concentration–effect relationship of adalimumab in rheumatoid arthritis

Molecular Analysis of Inflammatory Bowel Disease: Clinically Useful Tools for Diagnosis, Response Prediction, and Monitoring of Targeted Therapy

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