Optimizing immunoglobulin G therapy in chronic autoimmune neuropathies.

Abstract

Prolonged intravenous immunoglobulin (IVIg) therapy is frequently used for the treatment of chronic autoimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Recent studies of the electrophysiology and immunology of various neurological diseases, including CIDP, suggest that antibody-induced reversible dysfunction of nodes of Ranvier plays an important role in conduction block and morbidity 1. This may be more important, at least in the short term, than demyelination or axon destruction. The IVIg doses and dosing intervals are usually chosen empirically due to a paucity of data from dose-response and pharmacodynamic studies. The use of 2 g/kg as loading dose and maintenance doses of 1 g/kg every 3–4 weeks are common. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines suggest that the dose and frequency of IVIg should be tailored to an individual patient's needs 2. However, there are no recommendations as to how this can be achieved or the outcomes upon which adjustments in therapy should be based. Clinical observations suggest that with currently used immunoglobulin (Ig) regimens the beneficial effects of each dose of IVIg may be transient, wearing off before the next cycle of treatment is required. These observations have been confirmed by case reports. A patient with CIDP repeatedly showed improvement in ankle dorsiflexion over the first 5–9 days following the administration of IVIg. The improvement was sustained for approximately 10 days but then declined, reaching pretreatment levels by the end of the month 3. These periodic fluctuations in strength were also reported in a patient with MMN on monthly IVIg therapy 4. However, this patient was switched to subcutaneous immunoglobulin (SCIg) therapy and, with a 25% increase in total monthly dose, his disease stabilized. Weekly SCIg has been investigated as a means of continuously maintaining high serum IgG levels, resulting in stabilization of neuromuscular function in CIDP and MMN patients 5–8. Significant variations in IgG metabolism have been reported among patients with CIDP 9. These differences were unrelated to the administered dose, weight, body mass index or degree of functional improvement. However, the patient-specific post-infusion rise in IgG levels, which may be dependent upon the individual rate of IgG metabolism, may explain the interpatient differences in infusion frequency requirements. The optimum dosage and frequency of IVIg infusions appears to be patient-specific 9. It has been shown that actual doses and dosing intervals vary from conventional empirical dosing, suggesting that physicians may already be adjusting doses based on the individual patient's clinical condition and treatment response 10. A prospective study has shown that CIDP patients maintain strength optimally when their IgG levels reach a plateau supported by infusions as frequent as once every 10 days. The intra- and interpatient variability in IgG may indicate that individualized constant levels of IgG facilitate achieving clinical stability 11. Overall, these studies show that many patients with CIDP have increased benefit when IVIg is administered at more frequent intervals, with 30–60% of patients showing improvement when IVIg is administered at intervals of 10–14 days or less 9–11. An ongoing study supported by CSL Behring in collaboration with AxelaCare has demonstrated that grip strength and disability measurements performed frequently by the patient at home can be reported wirelessly, collected by a database service, and reported to the physician 12. This information can prove useful for assessing the extent and duration of responses to individual IgG doses. In addition, this type of frequent data collection can be used to identify patients who would benefit from weekly SCIg rather than IVIg every 3−4 weeks and those in whom IgG therapy is ineffective. Currently, Ig replacement therapy is widely used in the treatment of chronic autoimmune neuropathies. Individualization of IgG treatment regimens may optimize efficacy and minimize disability. Further studies are needed to determine whether patient-specific regimens result in improved long-term outcomes.