Serious Adverse Effects From IVIG Treatment Associated With Certain Preparations and Patient Risk Factors

Immunoglobulin is used in the treatment of multiple diseases and is typically well-tolerated, but a study published in Frontiers in Immunology highlights that some adverse effects, while rare, are serious. These severe adverse effects are commonly associated with specific immunoglobulin preparations and individual differences in patients, and measures should be taken by those administering the treatment to assess patient risk factors, according to the authors.

Adverse effects from intravenous immunoglobulin (IVIG) tend to be mild, but moderate and severe adverse effects have been observed. Mild adverse effects include light headache, fever, chills, and fatigue, and can typically be alleviated through slowing the rate of infusion or administering antihistamines and nonsteroidal anti-inflammatory drugs (NSAIDs). Moderate adverse effects include chest pain, anhelation, vomiting, arthralgia, and severe headache, which can require the infusion to be discontinued or antihistamines and NSAIDs to be administered. Severe adverse effects include hypertension, anaphylaxis, bronchospasm, and altered consciousness, all of which require infusion to be stopped immediately and for appropriate medical attention to be provided.

Studies have found that adverse effects were reported more often in patients treated with immunoglobulin products that contained a concentration of IgA higher than 15 micro-g/ml, and that a high titer of anti-RhD also increased the occurrence of adverse effects. Further, preparations of IVIG from different manufacturers have different excipients that may increase the rates of adverse effects for patients with specific conditions, including sucrose for patients with renal failure, glucose for patients with diabetes, maltose for patients with glucose fluctuation, sorbitol for patients with hereditary fructose intolerance, and high IgA for patients with a risk of anaphylaxis.

The investigators said that the majority of adverse effects are associated with high doses of immunoglobulin. Determining individualized dosages to guarantee the efficacy of therapy and minimize adverse effects is an urgent focus, they noted.

A number of different measures have been utilized to prevent or minimize the occurrence of immunoglobulin-related adverse effects, including slowing the infusion rate, premedication with antihistamines, corticosteroids, or NSAIDs, prehydration with saline, and switching from IVIG to another preparation of immunoglobulin, like subcutaneous immunoglobulin (SCIG). However, the authors note that the efficacy of these measures has been reported only in case controlled or small sample size studies and should be verified by randomized controlled studies or head-to-head studies with larger sample sizes.

The study authors noted that the adverse effects experienced by patients receiving IVIG are rarely disabling or fatal, and the treatment of these effects mainly involves supportive measures. The majority of affected patients have a good prognosis, they found.

REFERENCE

Yi Guo, Xin Tian, Xuefeng Wang, Zheng Xiao. Adverse effects of immunoglobulin therapy. Front Immunol. 2018; 9: 1299. doi: 10.3389/fimmu.2018.01299