Plasma infliximab monitoring contributes to optimize Takayasu arteritis treatment: a case report

Sho Masui,Hirofumi Shibata,Junko Takita,Kazushi Izawa,Atsushi Yonezawa,Makoto Hayakari,Kayoko Asakura,Kazuo Matsubara,Masahiko Isa,Takahiro Yasumi,Ryuta Nishikomori,Risa Taniguchi

doi:10.1186/s40780-019-0136-4

Abstract

BackgroundInfliximab (IFX), a mouse-human chimeric monoclonal antibody against human tumor necrosis factor alpha, is used in refractory cases of Takayasu arteritis. Several factors influence the pharmacokinetics of therapeutic antibodies including IFX. Monitoring plasma levels of IFX could be a useful approach in optimizing treatment via individual dose adjustment.Case presentationHere, we report the case of a 4-year-old Takayasu arteritis girl who was resistant to standard therapy. IFX was started at 5 mg/kg (day 0). C-reactive protein (CRP) levels decreased from 8.7 (day 0) to 1.6 mg/dL (day 10). CRP levels were thereafter elevated again on day 23 (9.0 mg/dL), and body fluid leakage at the inflammation site in the legs was observed. Trough IFX levels decreased from 23.6 (day 10) to 2.5 μg/mL (day 23). Based on the trough levels, IFX was given biweekly at 8 mg/kg. Plasma IFX levels gradually increased, and CRP levels decreased to around 2 mg/dL. A similar pattern -initial decreases followed by increases- was observed between clinical course of IFX and IgG levels. It was speculated that IgG and IFX losses were due to fluid leakage from the patient’s necrotizing legs.ConclusionsMonitoring of plasma IFX levels can be a potential tool to optimize the treatment in Takayasu arteritis patients.

Highlights

BackgroundInfliximab (IFX), a mouse-human chimeric monoclonal antibody against human tumor necrosis factor alpha (TNF-α), is used in the treatment of several autoimmune diseases
Infliximab (IFX), a mouse-human chimeric monoclonal antibody against human tumor necrosis factor alpha, is used in refractory cases of Takayasu arteritis
It has been reported that several factors influence the pharmacokinetics of therapeutic antibodies, such as development of anti-drug antibodies (ADAs) [1,2,3] and nephropathy [4]

Summary

Background

Infliximab (IFX), a mouse-human chimeric monoclonal antibody against human tumor necrosis factor alpha (TNF-α), is used in the treatment of several autoimmune diseases. We report the case of a 4-year-old girl with Takayasu arteritis, in whom monitoring of plasma IFX levels was useful as a means of adjusting the regimen of IFX administration. Blood flow decreased in her legs, and part of her right leg became necrotic. As she had been resistant to standard therapy with prednisolone or tocilizumab without monitoring plasma concentrations, we started to administer IFX (day 0). Based on the clinical courses of blood CRP and IFX levels (Fig. 1), trough IFX levels were decreased from 23.6 μg/mL (day 10) to 2.5 μg/mL (day 23). Plasma IFX levels gradually increased, and CRP levels decreased to around 2 mg/dL 40 days after IFX administration. It is noteworthy to mention that a similar pattern -initial decreases followed by increases- was observed in the clinical courses of IFX and IgG (Fig. 1)

Discussion

Conclusions