Intravenous immunoglobulin: pharmacological properties and use in polyneuropathies

Abstract

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 This review includes a description of the composition, pharmacokinetics, and mechanisms of action of IVIg. The second part of the paper provides an overview of the immune-mediated polyneuropathies in which IVIg is a first-line therapy, with special focus on the pathomechanism of the diseases, the mechanisms of action of IVIg, and of the main results of clinical trials supporting the evidence of its efficacy. Composition of IVIgIVIg is a complex preparation pooled from a minimum of 1000 and up to 60,000 donors, [6,7]. The anti-idiotypes can block the antigen-binding site of the pathological antibody.IVIg preparations contain many idiotypes and antibodies against several receptors as well. See Table 2 for details [8,9].At first, IVIg was used in a concentration of 5%, but subsequently, formulations with higher concentrations of 10-12% were also developed, which permitted the lowering of the volume load and the shortening of the time of administration. Formulations for subcutaneous use (SCIg) are available since the 1980s, which permit steadier IgG levels and a more favorable systemic side effect profile, except for the higher incidence of local reactions. Several brands of IVIg are available, with each considered to be a distinct product with a unique composition and different excipients. The products differ with regard to the production process, viral inactivation, purification, IgA content, sodium content, and the applied stabilizers, and are associated with different risks of adverse effects, depending predominantly on the IgA content, the osmolarity, and the stabilizers used.In recent years, significant advances have been achieved in the production process of IVIg preparations with regard to purity, pathogen inactivation, and stabilization. Cold alcohol fractionation is used to isolate the immunoglobulin-containing plasma fraction, which is further purified through multiple steps of precipitation and can also be combined with ionexchange chromatography, processes resulting in a highly purified polyvalent IgG product 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 PharmacokineticsThe dose of IVIg used for the treatment of immunodeficient conditions is 0.4-0.6 g/kg, administered every 3 to 4 weeks. Once the diagnosis is set, a continuous replacement therapy is to be initiated, which should not be interrupted. Some patients require higher doses of up to 0.8 g/kg. Doses exceeding this level have not been evaluated [13]. The total dose used in autoimmune/inflammatory diseases is 2 g/kg, administered in 2-5 consecutive days. This dose was introduced to clinical practice after the observation of a dramatic increase ...

Idiopathic systemic capillary leak syndrome (Clarkson disease)

“…82, 83 The mechanism of action of IVIG in SCLS is unknown, but we speculate that anti-idiotypic effects on the putative monoclonal autoantibody or neutralization of proinflammatory cytokines by antibodies present in IVIG preparations are two possible mechanisms by which IVIG exerts its prophylactic effects in SCLS. Over the last 8–10 years, monthly prophylaxis with IVIG has become the most commonly applied therapy in the NIH cohort.…”

Monoclonal Antibodies - Addressing the Challenges on the Manufacturing Processing of an Advanced Class of Therapeutic Agents

“…In particular, intravenous immunoglobulin (IVIG) is used as a replacement therapy in immunodeficient individuals, who are unable to create their own effective immune responses [32]. IVIG can also be used to suppress the pathological immune responses that occur in patients with autoimmunity [33]. IVIG formulations are prepared from the human serum IgG fraction, which is pooled from a minimum of 1000 up to 60,000 donors [34].…”

A pilot study of high‐dose intravenous immunoglobulin 5% for autism: Impact on autism spectrum and markers of neuroinflammation

“…Consequently, a treatment that reduces inflammation may be beneficial in some patients with autism. Intravenous immunoglobulin (IVIG) suppresses systemic inflammation and has long been used in the treatment of inflammatory conditions and autoimmune disease [Dalakas, ; Dezsi, Horvath, & Vecsei, ; Dwyer, ; Emmi & Chiarini, ; Lünemann, Quast, & Dalakas, ; Nikolov, Reisinger, & Schwarz, ; Nimmerjahn & Ravetch, ]. IVIG has been used to treat autism in three phase 1 clinical trials [DelGiudice‐Asch et al, ; Gupta et al, ; Plioplys, ], all with a low‐dose regimen (up to 400 mg/kg) infused at 4‐week intervals and with a relatively short duration of treatment and follow‐up, in a total of 42 children (30 male and 12 female), aged between 3 and 17 years.…”