Clinical applications of intravenous immunoglobulins (IVIg) – beyond immunodeficiencies and neurology

Abstract

SummaryThe clinical use of intravenous immunoglobulin (IVIg) has expanded beyond its traditional place in the treatment of patients with primary immunodeficiencies. Due to its multiple anti-inflammatory and immunomodulatory properties, IVIg is used successfully in a wide range of autoimmune and inflammatory conditions. Recognized autoimmune indications include idiopathic thrombocytopenic purpura (ITP), Kawasaki disease, Guillain-Barré syndrome and other autoimmune neuropathies, myasthenia gravis, dermatomyositis and several rare diseases. Several other indications are currently under investigation and require additional studies to establish firmly the benefit of IVIg treatment. Increasing attention is being turned to the use of IVIg in combination with other agents, such as immunosuppressive agents or monoclonal antibodies. For example, recent studies suggest that combination therapy with IVIg and rituximab (an anti-CD20 monoclonal antibody) may be effective for treatment of autoimmune mucocutaneous blistering diseases (AMBDs), with sustained clinical remission. The combination of IVIg and rituximab has also been used in the setting of organ transplantation. Firstly, IVIg Ϯ rituximab has been administered to highly human leucocyte antigen (HLA)-sensitized patients to reduce anti-HLA antibody levels, thereby allowing transplantation in these patients. Secondly, IVIg in combination with rituximab is effective in the treatment of antibody-mediated rejection following transplantation. Treatment with polyclonal IVIg is a promising adjunctive therapy for severe sepsis and septic shock, but its use remains controversial and further study is needed before it can be recommended routinely. This review covers new developments in these fields and highlights the broad range of potential therapeutic areas in which IVIg may have a clinical impact.

Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

“…At the current maximal dosing regimens, only partial and unsustained responses are obtained in many instances (2,4). In addition, the long infusion times (4-6 h) associated with the high volume of IVIg treatment consume significant resources at infusion centers (8) and negatively affect patient-reported outcomes, such as convenience and quality of life (10). Developing therapeutic alternatives that could leverage the broad biological activities of IVIg and simultaneously, provide more consistent and potent anti-inflammatory activity with minimal inconvenience would be highly valuable to clinicians and patients.…”

“…Although beneficial in numerous indications, IVIg preparations have distinct limitations, such as variable efficacy, clinical risks, high costs, and finite supply (2,3,8). Different IVIg preparations are frequently treated as interchangeable products clinically, but it is well-known that significant differences in product preparations exist that may impact tolerability and activity in selected clinical applications (9).…”

Catastrophic antiphospholipid syndrome (CAPS)

“…IVIG should be specially indicated in situations where there is concomitant infection because of its role as immunomodulator rather than immunosuppressor [18].…”

Experience with IgM-Enriched Immunoglobulins as Adjuvant Therapy in Septic Patient after Redo Cardiac Surgery

“…IgM antibodies play a key role in clearing pathogens and enhance primary immune response [12]. There have been numerous recent advances in understanding of the mechanisms of action of IVIG [13], but the optimal timing of administration, adequate dose of IgM preparations as well as target group still remain unsettled [14]. According to Molnar et al, the early administration of IgM preparation has beneficial effects in treatment of critically ill patients [7].…”