Stéphanie Willot | Search PubMed

PubMed2006

No association between C-reactive protein gene polymorphisms and decrease of C-reactive protein serum concentration after infliximab treatment in Crohn's disease.

We recently showed an association between the FCGR3A V/F polymorphism and the biological response [assessed on the basis of a C-reactive protein (CRP) concentration decrease] to infliximab in Crohn's disease. The CRP and FCGR3A genes are located on the same 1q23 locus. The present study aimed: (i) to exclude a linkage disequilibrium (LD) between the two genes and (ii) to study the association between CRP polymorphisms and the response to infliximab, particularly the decrease in CRP after treatment, in Crohn's disease patients. FCGR3A (V/F) polymorphism and three CRP polymorphisms (-717G/A, 1444C/T, CRP 4A/G) were determined in 206 healthy blood donors and 189 Crohn's disease patients who had received infliximab for either refractory luminal or fistulizing Crohn's disease. Clinical response was defined as complete, partial or absent according to the same definition as in controlled trials. The biological response was defined on the basis of CRP decrease. There was no LD between CRP and FCGR3A in healthy donors or Crohn's disease patients. CRP polymorphisms had no impact on CRP decrease after infliximab. The proportions of Crohn's disease having a positive clinical or biological response were not statistically different among the various genotypes of CRP polymorphisms. There was no LD between CRP and FCGR3A polymorphisms. CRP polymorphisms were not associated with the response to infliximab in Crohn's disease.

Adolescent↗

PubMed2006

An enzyme-linked immunosorbent assay for therapeutic drug monitoring of infliximab.

An enzyme-linked immunosorbent assay (ELISA) measuring serum infliximab concentrations in treated patients was developed. Microtiter plates were sensitized with tumor necrosis factor alpha (TNF-alpha) and saturated with phosphate-buffered saline (PBS) containing 1% bovine serum albumin (BSA). Samples diluted 1:100 in PBS-1% BSA were added and bound infliximab was detected using peroxidase-conjugated goat anti-human immunoglobulin G specific for Fc fragment (HRP-anti hIgG). Reading was performed using an ELISA plate reader. The limit of detection, calculated by assaying 10 replicates of a drug-free serum sample or blank sample and defined as the lowest concentration distinguishable from zero at 2 standard deviations, was 0.014 microg/mL. Each quality control sample was tested on 7 occasions on 1 day and on 5 separate days. The intraday precision indices of the method were (percent coefficients of variation, CV%) 11.7%, 6.2%, and 6.9% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias measures (percent deviation) were -5.5%, -1.9%, and -7.9%, respectively. The between-days precision was 9.8%, 5.3%, and 5.3% for 0.04 microg/mL, 2 microg/mL, and 4.5 microg/mL, respectively. The corresponding bias were +0.3%, -0.3%, and -7.8%, respectively. Lower limit of quantitation and upper limit of quantitation were 0.04 microg/mL and 4.5 microg/mL, respectively. Trough serum concentrations of infliximab were measured in 6 adult patients with various diseases and in 5 pediatric patients with Crohn's disease. For the latter group, samples drawn 1 hour after the end of the infusion and repeated measurements also were available. Data were described using a 1-compartment population pharmacokinetic model. Terminal elimination half-life was 10.9 days. This method is rapid, accurate, and reproducible, and may be useful in therapeutic drug monitoring of infliximab.

Adolescent↗