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Research paper
Pharmacokinetics of intravenous immunoglobulin in multifocal motor neuropathy
  1. Lotte Vlam,
  2. Elisabeth A Cats,
  3. Eline Willemse,
  4. Hessel Franssen,
  5. Jelena Medic,
  6. Sanne Piepers,
  7. Jan H Veldink,
  8. Leonard H van den Berg,
  9. W-Ludo van der Pol
  1. Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr W-Ludo van der Pol, Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery Medical Center Utrecht, Department of Neurology G 03.228, Heidelberglaan 100, Utrecht 3508 GA, The Netherlands; W.L.vanderPol{at}umcutrecht.nl

Abstract

Background Multifocal motor neuropathy (MMN) is often responsive to treatment with intravenous immunoglobulin (IVIg), but the optimal dose and intervals of IVIg maintenance treatment have not been established. Increase in IgG concentration (ΔIgG) after IVIg infusion has recently been identified as determinant of outcome in Guillain-Barré syndrome. ΔIgG may therefore represent a potentially useful biomarker to optimise IVIg dosing in patients with MMN.

Objective The aims of this study were to determine variability of IVIg pharmacokinetics in patients with MMN in relation to treatment response, and to establish whether interindividual differences in IVIg pharmacokinetics were associated with genetic polymorphisms of the endothelial IgG receptor (FcRn) which determines IgG half-life.

Methods Twenty-three patients with MMN receiving their first IVIg treatment at a cumulative dose of 2.0 g/kg in 5 days were included. A good treatment response was defined as an increase in muscle strength of at least one Medical Research Council point in minimally two muscle groups. IgG concentrations in serum were determined at baseline, at day 1 and day 5 of the IVIg course, and 3 weeks after treatment. FcRn copy number variation and differences in repeat length of the variable number of tandem repeats in the FcRn gene were determined by quantitative PCR and Sanger sequencing.

Results Seventeen patients (74%) had a good response to treatment. Total IgG and ΔIgG levels showed large variation between patients. Mean ΔIgG was higher in IVIg responders than in non-responders, with the largest difference on day 1 (11.1 g/L vs 4.5 g/L, p=0.06), but our study lacked power to show statistically significant differences. Genetic variation in the FcRn gene was not associated with ΔIgG levels or response to treatment.

Conclusions IVIg pharmacokinetics varies in patients with MMN and may be associated with clinical response.

  • Neuroimmunology
  • Neuropathy

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