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Home arrow Environment arrow Inflammatory Disorders of the Nervous System: Pathogenesis, Immunology, and Clinical Management
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Intravenous Immunoglobulins (IVIG)

IVIG has been used as a preferred treatment for CIDP for almost two decades.

Axonal loss, as demonstrated by muscle atrophy clinically or low or absent motor potentials on EMG, is an important predictor of lack of response to IVIG [138].

The mechanism of action of IVIG in CIDP is multimodal and includes blocking or decreased production of pathogenic antibodies and decreased complement deposition [139]. IVIG also modulates cellular immune system and decreases the concentration of adhesion molecules and cytokine secretion by the endothelial cells [139]. Wong et al. showed significantly reduced ratio of sialylated/agalactosylated IgG-Fc in CIDP patients, and decrease in that ratio was associated with more severe disease [140]. Treatment with IVIG resulted in increased levels of sialylated IgG-Fc which correlated with clinical improvement [140]. The effect of IVIG on the T cell profile and Treg cells is described above [32].

IVIG is administered at 2 g/kg divided over 3-5 days and followed by maintenance infusions of 0.5-1 g/kg every 2-4 weeks. The frequency and dose of the maintenance therapy are adjusted based on the clinical response of the patient. IVIG is overall well tolerated by most patients. Infusion reactions include chills, rash, nausea, headache, and myalgias. These can be prevented or improved by premedicating patients with acetaminophen and diphenhydramine and slowing the infusion rate [141]. Other serious but not common side effects include renal failure (typically in patient with underlying renal insufficiency), congestive heart failure (in patients with pre-existing heart disease), anaphylactic reactions (more common in IgA- deficient patients), and thromboembolic events such as deep venous thrombosis and ischemic stroke. Other rare side effects include aseptic meningitis, neutropenia, and uveitis [141]. The efficacy of IVIG was proven in the CIDP Efficacy (ICE) trial, which is thus far the largest and longest (up to 48 weeks) randomized, double-blind, placebo-controlled, crossover trial in this disease. The trial used a loading dose of 2 g/kg administered over 2 to 5 days, followed by maintenance infusions of 1 g/kg administered every 3 weeks for 6 months, and demonstrated improvement in adjusted INCAT disability score and grip strength and lower rate of relapse compared to the placebo arm [142].

Subcutaneous IG (SCIg) is being investigated as an alternative to IVIG in those patients who cannot tolerate IVIG infusions. These have been used for two decades for other autoimmune disorders and require more frequent administration but at lower doses. Recent randomized trials showed efficacy of SCIg in improving the muscle strength in CIDP patients who were previously responsive to IVIG [143, 144].

Two IVIG formulations (Gammagard 5% IVIG and Kiovig 10% IVIG) were compared for their efficacy and side effect profile in a study, which demonstrated similar efficacy and side effect profile [145]. No randomized trials of IVIG versus SCIg have thus far been conducted. The effectiveness of IVIG versus pulsed IV methylprednisolone (500 mg IV daily for 4 days, followed by a monthly administration for 6 months) was compared in a randomized controlled trial, which showed that IVIG was less frequently discontinued because of inefficacy or side effects at 6 months (87.5% vs. 47.6%, respectively); however, the relapse rate after discontinuation was higher in the IVIG group, while in the patients who remained in the methylprednisolone group, no patients relapsed at 6 months of treatment [146].

 
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