Pharmacokinetics of IV Immunoglobulins and Outcome in GBS

Abstract & Commentary

By Norman Latov, MD, PhD, Professor of Neurology and Neuroscience, and Director of the Peripheral Neuropathy Center, Weill Medical College of Cornell University Dr. Latov serves as consultant to Quest Diagnostics, Talecris Biotherapeutics, CSL Behring Biotherapies, Baxter Bioscience, and Octapharma AG, and owns stock in Therapath LLC. This article originally appeared in the February 2010 issue of Neurology Alert. It was edited by Matthew Fink, MD, and peer reviewed by M. Flint Beal, MD. Dr. Fink is Vice Chairman, Professor of Neurology, Weill Cornell Medical College; Chief, Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital, and Dr. Beal is Professor and Chairman, Department of Neurology, Cornell University Medical College. Drs. Fink and Beal report no financial relationships relevant to this field of study.

Synopsis: Fixed dose of IVIg may not be effective in all patients with GBS.

Sources: Kuitwaard K, et al. Pharmacokinetics of intravenous immunoglobulin and outcome in Guillain-Barré syndrome. Ann Neurol 2009;66:597-603. Cornblath DR, Hughes RAC. Treatment for Guillain-Barré syndrome. Ann Neurol 2009;66:569-570.

Kuitwaard et al reviewed data from 174 patients with Guillain-Barré Syndrome (GBS) who had previously participated in two randomized clinical trials using intravenous gamma globulins (IVIg). All patients were unable to walk unaided and received a standard dose of IVIg. The data analysis revealed considerable variation in the increase in serum IgG (DIgG) at two weeks after IVIg treatment, but the patients with a low DIgG recovered significantly more slowly, and fewer reached the ability to walk unaided at six months. In a multivariant analysis adjusted for other known prognostic factors, a low DIgG was independently associated with poor outcome. The authors suggest that patients with a small increase in serum IgG level may benefit from a higher dosage or second course of IVIg.

In an accompanying editorial, Cornblath and Hughes stress the need for improvement in the management of GBS, as at one year, 2%-3% of those with severe GBS will have died and 15%-18% will still have significant disability. They note the absence of studies to determine the optimal dose of IVIG in GBS, and voice support for additional clinical trials with higher or repeat doses.

Commentary

The preferred treatment for GBS is IVIg, although questions remain regarding the dose, timing, repeat treatment, and mechanism of action.

The findings by Kuirwaard et al point to the importance of identifying biomarkers that predict response to treatment. Differences can be due to underlying disease mechanisms, or to differences in the interaction of the IVIg with the host immune system. In chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), for example, recent studies show that the response to IVIg is influenced by polymorphism in TAG-1,1 and may be associated with upregulation of the expression of Fcgamma receptor IIB on B cells.2 Following DIgG in patients with GBS treated with IVIG might be such a biomarker that would help guide treatment.

Another important observation is that not all patients with GBS are the same, which puts current guidelines into question.3 This study, as an example, provides a rationale for giving patients an additional dose of IVIg if there is a relapse or no response to the initial treatment. Restricting the treatment recommendations to patients who are no longer ambulatory, as only such patients were included in clinical trials, without comparing other time points, may also be inappropriate given our inability to identify those patients who will progress to severe disability.

References

1. Iijima M, et al. Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP. Neurology 2009;73:134-138.

2. Tackenberg B, et al. Impaired inhibitory Fcgamma receptor IIB expression on B cells in chronic inflammatory demyelinating polyneuropathy. Proc Natl Acad Sci U S A 2009;106:4788-4792.

3. Hughes RA, et al. Practice parameter: Immunotherapy for Guillain-Barré syndrome: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003;61:736-740.