Immunoglobulin G level variations in treated chronic inflammatory demyelinating polyneuropathy: clues for future treatment regimens?

Intravenous immunoglobulins (IVIg) are effective for treating chronic inflammatory demyelinating polyneuropathy (CIDP), although treatment needs are variable and need to be individualized. Dose and frequency requirements are not currently predictable in advance. In Guillain-Barré syndrome, IVIg interpatient pharmacokinetic variations have been demonstrated in relation to clinical outcome. We studied 15 patients with CIDP following two routine courses of IVIg. IgG levels were assessed pretreatment and 14 days post-treatment. Best clinical response (BCR) was ascertained in each case, predefined, according to individual patients' circumstances, on the 10 m walk, or MRC sum score, or Jamar grip dynamometry. Correlations between IgG level variations, doses administered, weight, body mass index, BCR and infusion interval were determined. Postinfusion rise in IgG levels were correlated in individual patients (p = 0.005), but interpatient variability was high. No correlations were ascertained between IgG level variation and weight, body mass index, BCR, total dose of IVIg administered, or dose of IVIg administered per kilogram per week. There were significant correlations between total dose administered and post-infusion IgG level at 14 days (p = 0.004) and between infusion interval and mean rise in IgG level (p = 0.001) These findings suggest significant variability in IgG metabolism between patients, unrelated to minimal effective dose administered, weight, body mass index or degree of functional improvement. Required frequency of IVIg infusions may, however, importantly relate to patient-specific post-infusion rise in IgG levels hence possibly explaining inter-patient differences in treatment frequency needs. IgG level monitoring may be helpful in establishing optimum treatment regimens in individual cases.

Thromboembolic complications of intravenous immunoglobulin therapy in patients with neuropathy: a two-year study.

BACKGROUND: The incidence and determinants of thromboembolic complications (TEC) of intravenous immunoglobulin (IVIg) therapy in patients with dysimmune neuropathy are uncertain. METHODS: We performed a retrospective study of patients with dysimmune neuropathy seen at our institution and treated with IVIg, over a 24-month period. RESULTS: Sixty-two patients were treated with a total of 616 courses of IVIg. TEC occurred in 7 patients. In 5, these occurred within 14 days after IVIg infusion ("early TEC"). Early TEC were significantly more frequent after courses administered to IVIg-naïve patients (3/25 vs. 2/591 courses; p<0.001), but incidences were comparable in newly- vs. previously-treated patients (3/25 vs. 2/44 patients; p=0.34). Early TEC included 2 cases of myocardial infarction, one of acute coronary syndrome, one of deep vein thrombosis (DVT) with pulmonary embolism and one of isolated DVT. Mean dose per course was comparable in affected and unaffected patients (p=0.47), but administration of daily doses ≥ 35 g correlated significantly with occurrence of early TEC (p=0.028). Previous coronary disease (p=0.037) and immobility at time of treatment (p=0.049) were independent predictors of early TEC. Patients with early TEC had significantly more risk factors (p<0.001), and were significantly more likely to have ≥ 4 risk factors (p=0.006), than those without early TEC. CONCLUSION: The risk of TEC with IVIg is not negligible in patients with neuropathy. Although higher with a first-ever infusion, the general risk may be comparable in IVIg-naïve and previously-treated patients. Administration of daily doses ≥ 35 g of IVIg may carry a greater risk of early TEC. Coronary disease, immobility at time of treatment, presence of ≥ 4 risk factors, should lead to caution and consideration of alternative treatments.