Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe.

Kerr, Jacqueline; Quinti, Isabella; Eibl, Martha; Chapel, Helen; Späth, Peter Julius; Sewell, W A Carrock; Salama, Abdulgabar; van Schaik, Ivo N; Kuijpers, Taco W; Peter, Hans-Hartmut (2014). Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe. Frontiers in immunology, 5(629), p. 629. Frontiers Research Foundation 10.3389/fimmu.2014.00629

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The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg" dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki' disease, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.

Item Type:

Journal Article (Further Contribution)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Späth, Peter Julius

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1664-3224

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Aniko Krebs

Date Deposited:

02 Jul 2015 13:33

Last Modified:

26 Jun 2016 02:05

Publisher DOI:

10.3389/fimmu.2014.00629

PubMed ID:

25566244

Uncontrolled Keywords:

IVIG; SCIG; dosing; immunomodulation; replacement therapy

BORIS DOI:

10.7892/boris.70074

URI:

https://boris.unibe.ch/id/eprint/70074

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