An Overview of Its Uses and Effectiveness
Its commonly known as IVIG, is a therapeutic preparation of concentrated immunoglobulins purified from pooled adult human plasma. IVIG contains predominantly immunoglobulin G (IgG) with a defined IgG subclass and immunoglobulin A (IgA) and immunoglobulin M (IgM) concentration. It is administered intravenously to treat various immune deficiencies and autoimmune disorders.
Approved Uses of IVIG
IVIG has been approved for use in the following conditions:
– Primary immunodeficiency: IVIG is used as replacement therapy for patients with primary immunodeficiencies, including common variable immunodeficiency, X-linked agammaglobulinemia, and severe combined immunodeficiencies. It helps prevent recurring infections in such patients.
– Chronic inflammatory demyelinating polyneuropathy (CIDP): IVIG is effective at improving nerve conduction and reducing symptoms in CIDP patients. It is used as first-line treatment for this autoimmune disorder.
– Idiopathic thrombocytopenic purpura (ITP): In adults with ITP unresponsive to corticosteroids, IVIG induction therapy increases platelet counts and reduces bleeding risk.
– Kawasaki disease: When given along with aspirin, IVIG helps reduce the risks of coronary artery abnormalities in children with Kawasaki disease.
– B-cell chronic lymphocytic leukemia (CLL): IVIG is used in combination with fludarabine and cyclophosphamide for CLL patients with increasing lymphocyte counts or high tumour burden.
Mechanism of Action and Pharmacokinetics
The exact mechanism of IVIG’s therapeutic actions varies with the condition being treated. Some proposed mechanisms include:
– Replacement of missing antibodies in primary immunodeficiencies.
– Interference with Fc receptors on macrophages and suppression of the functions of complement components, attenuating autoimmune responses in conditions like CIDP and ITP.
– Blocking of activation and proliferation of autoreactive B-cells through anti-idiotypic antibodies.
– Modulation of cytokine expression through anti-cytokine antibodies.
After IV administration, IgG is distributed primarily in the intravascular compartment with a volume of distribution of 3 liters/70 kg. The average half-life is 31 days and steady-state levels are achieved after 3-4 months of repeated dosing. IVIG is not metabolized and is mainly cleared through the reticuloendothelial system and renal clearance.
Efficacy Studies
Numerous studies have demonstrated Human Immunoglobulin (pH4) for Intravenous Injection’s efficacy and safety profile in various approved conditions:
– In primary immunodeficiencies, IVIG treatment significantly reduces respiratory and other infections along with days missed from school/work. Monthly IVIG is as effective as weekly dosing.
– For CIDP, IVIG was shown to improve disability scores and nerve conduction compared to placebo in multiple randomized controlled trials. Most patients experience long-term benefit with maintenance therapy.
– In two meta-analyses, IVIG was found to increase platelet count and reduce bleeding in over 70% of adult ITP patients within 1-2 weeks of a single infusion. Response is sustained in many cases with maintenance treatment.
– In Kawasaki disease, IVIG plus aspirin therapy brought down coronary artery complications to less than 5%, establishing it as a first-line treatment alongside aspirin alone. IVIG non-responders may benefit from repeat infusions.
– As induction therapy for CLL, IVIG with chemoimmunotherapy improved response rates and time to treatment failure versus chemotherapy alone in a pivotal randomized trial.
Adverse Reactions and Monitoring
IVIG is generally well-tolerated though transient adverse effects like headache, fever, chills, and hypotension may occur in 30% of patients during or shortly after infusion. Severe rare reactions include anaphylaxis, thrombosis, and aseptic meningitis.
Patients must be monitored for renal function, as IVIG may precipitate acute renal failure in those with pre-existing renal insufficiency, diabetes, or volume depletion. Thrombotic events like stroke are also possible, especially in smokers or patients with other prothrombotic risk factors.
The dosage of IVIG must be tailored based on the indication, patient risk factors, and response. Periodic monitoring of trough IgG levels and clinical status aids dose adjustments over time in chronic conditions. Patient education on potential adverse effects is recommended.
Conclusion
With over 30 years of clinical use, intravenous immunoglobulin has established itself as an important treatment modality for a variety of immune deficiencies and inflammatory disorders. Extensive research supports its efficacy and generally good safety profile when administered properly. As an antibody replacement and immunomodulatory therapy, Human Immunoglobulin (pH4) for Intravenous Injection improves quality of life for many patients who may otherwise face chronic infections or disability from underlying conditions.