Pharmacokinetic study and Fcγ receptor gene analysis in two patients with rheumatoid arthritis controlled by low-dose infliximab

Abstract

The main aim of this study is to investigate the pharmacokinetics of infliximab and Fcγ receptor (FcγR) polymorphism in two patients with rheumatoid arthritis (RA) who were well controlled by low-dose infliximab. A 57-year-old woman (Patient 1) and a 67-year-old woman (Patient 2) had active RA despite methotrexate and prednisolone treatments. They improved after the addition of infliximab (3 mg/kg), but developed pneumonia and sepsis, respectively. Although the infliximab doses were reduced to 1.5 mg/kg and 1 mg/kg, respectively, clinical improvements were maintained. Blood samples were obtained at 1 h after infliximab administration and at eight weeks (just before the next dose). The elimination half-life was determined by the serum concentration of infliximab. We also analyzed the polymorphisms of FcγRIIA, FcγRIIIA, and FcγRIIIB for the genomic DNA samples from the two patients and three controls. Amplification of the FcγR-genomic regions in allotype-specific polymerase chain reactions was used to distinguish the genotypes. Decresed clearance of infliximab was proven by a pharmacokinetic study of these patients under low-dose infliximab therapy. 131H/H (FcγRIIA) and 176F/F (FcγRIIIA) were detected in both patients. NA1/NA2 and NA2/NA2 (FcγRIIIB) were detected in Patients 1 and 2, respectively. These patients were well controlled over the long term by low-dose infliximab. The mechanism of the reduced clearance of infliximab might possibly be explained in part by the FcγR polymorphisms.

Keywords::

• Infliximab
• Pharmacokinetics
• Fcγ receptor
• Polymorphism
• Rheumatoid arthritis