IVIg is a product made up of antibodies. It is typically prescribed to people with immune disorders who don’t make enough antibodies. Research continues to suggest new uses for IVIg, but many studies are still in the early phases. Read on to learn more about the main uses and side effects of IVIg.
Disclaimer: The contents of this post are solely informational. Our goal is to outline the information available in the clinical and scientific literature. Please discuss your health concerns and medications with your doctor.
What is IVIg?
Overview
Intravenous immune globulin (IVIg) is a mixture of antibodies that is used to treat a variety of immune system disorders. It is made by gathering blood from thousands of donors to create a concentrated collection of antibodies.
Some people may need IVIg because their body does not make enough antibodies on its own. In this case, IVIg provides new antibodies for the immune system to help fight infections.
Another reason why people may use IVIg is if their immune systems have begun attacking their body’s own cells. The components inside IVIg can stop the immune system from thinking that normal, healthy cells are a threat.
IVIg is used in many conditions including genetic disorders, autoimmune diseases, and infections [1].
The mechanism behind how IVIg works is still not fully understood. Nonetheless, the use of IVIg is growing in many countries despite its very high cost [2+].
The World Health Organization has placed IVIg on its List of Essential Medicines. This list details the most effective and safe medications needed for basic healthcare systems.
How IVIg Is Produced
IVIg is created from the blood of between 1,000 to 15,000 individual donors. Depending on the manufacturer, different amounts of donors are used [1].
All IVIg products contain mostly IgG antibodies. This mirrors the human immune system where IgG is the most common antibody [3].
Some products may also contain trace amounts of IgA and IgM. These types of antibodies are less desirable than IgG because they are less effective. In addition, some people may experience a severe allergic reaction to IgA [3].
Various cells and proteins that are a part of the immune system can also be present in IVIg [1].
Once the use of IVIg became widespread, the World Health Organization published standards on how IVIg should be manufactured. These requirements include [4]:
- Use at least 1,000 individual donors
- Minimize the presence of IgA
- Do not include harmful preservatives
- Do not modify IgG molecules
Proposed Mechanism of Action
The way IVIg works is complex and not fully understood. Scientists believe that the effectiveness of IVIg is most likely due to multiple mechanisms of action.
The simplest way IVIg works is by providing extra antibodies to the immune system. Once it enters the blood, the antibodies inside IVIg may go on to kill bacteria or viruses [5].
IVIg is also hypothesized to increase the growth of cells that support the immune system. These cells help in immune system communication and identifying harmful substances [5].
Another way IVIg may work is by eliminating defective antibodies. In autoimmune disorders, defective antibodies mistakenly attack normal human cells. Research suggests that IVIg is able to remove and stop the production of these self-attacking antibodies [5].
Studies point out that, at high doses, IVIg blocks the complement system. The complement system normally improves the function of antibodies. This can be a problem when defective antibodies attack human cells. IVIg stops the complement system from activating, which prevents inflammation and organ damage [5].
Parts of IVIg can also bind to different white blood cells to control their activity and production. By reducing white blood cell activity, IVIg is believed to help in many autoimmune disorders [5].
Some research suggests that IVIg may repair the protective layer on nerve cells. Scientists are investigating whether IVIg prevents skin cells from dying in test tubes, which may turn out to be useful in severe skin reactions. Research on how IVIg works is ongoing and additional mechanisms of action may be discovered [6, 7].
Uses of IVIg
IVIG is given into a vein (intravenously), usually in a doctor’s office or hospital. It may also be given at home under specific arrangements and medical guidance.
1) Impaired Immune System
Genetic Disorders
Some genetic disorders reduce or completely block the body’s ability to create antibodies. People with these disorders are extremely vulnerable to infections [8+].
The most common treatment is IVIg, which replaces the missing antibodies in the immune system. For these genetic disorders, IVIg is usually given every 3 – 4 weeks for the rest of the individual’s life [8+].
One analysis of 17 different studies looked at 676 people who are unable to create any antibodies. They found that IVIg reduces the risk of infection and the need for hospitalization. They also show that IgG levels in the blood correlated to the risk of infection. An increase of 100 mg/dL of IgG decreased the risk of pneumonia by 27% [9].
Some people with this genetic disorder are able to create antibodies, but at a reduced rate. Observational studies of this disorder suggest that IVIg may also reduce the number of pneumonia cases and prevent lung damage [10, 11].
Leukemia
Leukemia is a type of bone marrow cancer that affects white blood cells. Some forms of leukemia can reduce antibody production which leads to recurrent infections.
IVIg is added to normal cancer therapy if infections become a concern. According to a review of 9 trials, IVIg reduces the frequency of infections. However, they also found IVIg does not reduce the overall risk of death [12].
A cost analysis determined that IVIg may not be a cost-effective treatment in this cancer. Most evidence suggests that the high cost of the drug and the inconvenience of constant treatments may outweigh the benefits that IVIg provides [13].
HIV in Children
HIV disease is caused by a viral infection that affects multiple cells in the immune system. Progressive decline in the immune system can eventually lead to AIDS. In AIDS, the body is especially vulnerable to infection.
In the past, IVIg was used in children with HIV to prevent infections. Older clinical trials show that IVIg decreases infection time and the frequency of hospitalizations [14, 15].
However, these studies were performed before newer HIV treatments were available. A new class of medications, called highly active antiretroviral therapy (HAART), has mostly replaced IVIg [16, 2+].
2) Autoimmune Diseases
Nerve Disorders
Many autoimmune diseases can affect the nerves. These disorders occur when antibodies attack nerves or the protective layer that surrounds them. This can lead to muscle weakness, decreased reflex response, and a loss of senses.
Treatment of these nerve disorders usually includes IVIg or plasma exchange (PE). PE works by filtering the blood and removing unwanted antibodies [17+].
An example of one of these nerve disorders is Guillain-Barré syndrome. According to a review of 12 clinical trials, IVIg and PE both improve recovery time in this disorder. There was no difference in effectiveness or side effects between the two [18].
Chronic inflammatory demyelinating polyneuropathy is another autoimmune disorder that affects the nerves. An analysis of 5 large reviews found that IVIg improves short-term disability in this disorder [19].
IVIg is preferred in children and for those with poor access to veins. Clinical trials have shown people are less likely to complete therapy with PE due to difficult vein access [19].
Research suggests IVIg may help in other nerve disorders as well. In one analysis, IVIg improved strength in 78% of people and reduced disability in 39%. A different long-term study found that IVIg may also repair nerve cells over time [20, 21].
Eye Disorders
IVIg may be helpful in a disorder called Graves ophthalmopathy. In this disorder, antibodies attack different tissues in the eyes which causes inflammation. Symptoms can vary from mild discomfort to severe swelling that requires urgent treatment [22].
The typical treatment for this disorder is steroids. Small studies show that IVIg and steroids are equally effective at improving eye symptoms. IVIg has less frequent and milder side effects compared to steroids [23, 24].
Birdshot retinochoroidopathy is a similar condition that involves eye inflammation. One study of 18 patients with this disease found that vision improved in half of the people who took IVIg [25].
Blood Disorders
Idiopathic thrombocytopenic purpura is an autoimmune disorder that causes red or purple spots on the skin. These spots can occur when antibodies mistakenly attack platelets in the blood. The destruction of platelets will reduce the blood’s ability to clot. This leads to internal bleeding that appears as spots on the skin.
Mild cases of this disorder usually don’t require treatment. Children can often recover on their own without medical help [2].
IVIg is used when there is a high risk of bleeding complications. It works by slowing the destruction of platelets by the immune system [26+].
Clinical trials suggest that IVIg may be more effective than steroids, a common treatment for this condition. IVIg increased platelet counts and reduced bleeding in children and adults. IVIg also has fewer side effects compared to steroids [27, 28, 29].
A different disorder, Henoch-Schonlein purpura, also leads to bright red spotting. The spotting in this disorder is caused by antibodies that clump together in the blood vessels. These antibody clumps cause inflammation and bleeding [30].
Although several case reports have suggested that IVIg may be helpful in these bleeding complications, clinical trials are lacking [31, 32].
Muscle Disorders
A rare muscle disorder called dermatomyositis causes serious inflammation in the muscles. Symptoms can include skin rash, worsening muscle weakness, weight loss, and fever. The exact cause of this inflammation is unclear, but it is likely an immune response to an infection.
This condition is normally treated with steroids and immune-suppressing medications [33].
A few studies have explored the use of IVIg. According to one trial, IVIg improved muscle symptoms in only 3 of the 11 people studied [34].
Another report found that IVIg improved symptoms in all 9 children who were studied. Researchers followed the children for 4 years and found that 6 of them were able to decrease their steroid dose while taking IVIg [35].
More research on the use of IVIg for symptoms of this disorder is needed.
Arthritis
Some forms of arthritis commonly affect children. Arthritis is an inflammation of the joints that can cause tiredness, flu-like symptoms, and pain. Antibodies attacking tissues in the joints cause this inflammation.
Normal treatment includes NSAIDs, steroids, or drugs that modify the immune system [2+].
One study examined the potential of IVIg in 27 children with arthritis. Researchers found IVIg improves fever symptoms and reduces the need for steroids. However, there was no effect on the overall progression of the disease [36].
In a clinical trial of 25 children, IVIg improved the symptoms of about 75% of participants. Once IVIg was stopped, the benefits quickly wore off [37].
More research is needed to determine the safety and effectiveness of IVIg in children with arthritis.
Pregnancy Complications
Antiphospholipid syndrome (APS) is an autoimmune disorder where antibodies attack a form of fat found in cells. This results in an increased risk of forming blood clots.
This disorder is a special concern in pregnant women. APS increases the risk of pregnancy complications such as miscarriage, early delivery, and stillbirth [38].
According to one small study, IVIg reduces the number of infant development problems and the need for intensive care [39].
However, a research review examining 13 studies found that IVIg increases the risk of pregnancy loss or premature birth [40].
More research is needed to determine the safety and effectiveness of IVIg in pregnancy.
Other Autoimmune Diseases
Research suggests IVIg may also be effective in [2+]:
- Multiple Sclerosis [41, 42, 43]
- Myasthenia gravis [44, 45]
- Severe rheumatoid arthritis [46, 47, 48]
- Still disease [49]
- Felty syndrome [50]
Further research is needed.
3) Infection-Related Diseases
Kawasaki Disease
Kawasaki disease mainly affects children and causes inflammation of the blood vessels. Symptoms include fever, rash, and redness of the mouth and tongue. This disease is believed to be triggered by an infection.
Doctors typically use IVIg therapy with aspirin during the first 10 days of the disease. This practice helps prevent blood vessels in the heart from weakening [51+].
An analysis of 16 clinical trials shows that IVIg reduces injury to the heart and decreases the duration of fever. They also found that a single high dose of IVIg was the most effective strategy [52].
Infection Caused by Organ Transplant
People that receive organ transplants must take medications that suppress their immune system. This must be done to ensure their body does not reject the new organ. However, these medications also put them at an increased risk for infections.
Certain viruses can cause severe lung inflammation in bone marrow transplant patients [53].
Studies show that high dose IVIg, combined with antiviral drugs, increases the chance of survival. One study of 25 people found that 52% of patients survived after taking IVIg + antiviral drugs. When patients only took antiviral drugs only 15% survived [54].
Another small study found that 7 of 10 patients on IVIg + antiviral drugs survived and had no recurrence of the disease after 10 months. In contrast, all of the patients that took only one of the medications did not survive [55].
More research is needed to determine the safety and effectiveness of IVIg in people with infection caused by organ transplants.
Infection of the Gut
Certain viruses can cause severe diarrhea in children. The virus infects the lining of the small intestine which causes inflammation.
Treatment primarily consists of making sure the patient is well hydrated [56].
One clinical trial has explored the use of IVIg in this infection, but more research is needed. Children who received IVIg had a quicker recovery and reduced hospital stay. This is one of the few instances where IVIg is taken by mouth [57].
Toxic Shock Syndrome
Toxic shock syndrome is a life-threatening disease caused by toxins. Some types of bacteria are able to produce toxins which trigger a massive response by the immune system. This causes fever and low blood pressure which eventually can lead to organ failure.
An observational study found that 67% of people treated with IVIg survived after 30 days. In the group that did not receive IVIg only 34% survived. Researchers suggest that IVIg should be researched as a potentially effective add on medication [58].
For now, the use of IVIg for toxic shock syndrome remains unproven due to a lack of clinical trials.
Other Infection-Related Diseases
IVIg has been suggested to be potentially effective in [2+]
- Cystic fibrosis [59]
- Post-surgery infection [60]
- Lower respiratory tract infection [61]
- Colon inflammation [62, 63]
However, these uses remain unproven. Clinical trials are needed.
4) Miscellaneous Uses
More research is needed to determine the safety and effectiveness of IVIg in the conditions outlined below. The existing studies had mixed findings.
Asthma
Asthma is caused by chronic inflammation in the airways of the lungs. Symptoms include shortness of breath, coughing, wheezing, and chest tightness.
Several studies have looked at IVIg’s potential in asthma. According to clinical trials, IVIg is no more effective than placebo in many cases. IVIg also does not reduce the frequency of infections [64, 65].
However, IVIg may be beneficial in people with immune system abnormalities and asthma. According to case reports, IVIg reduces the number of infections and reduces the severity of symptoms [2+, 66, 67].
Severe Skin Reactions
Toxic epidermal necrolysis and Stevens-Johnson syndrome are two forms of severe skin reactions. These reactions are most commonly caused by certain medications. The symptoms are intense blistering and peeling of the skin which requires hospitalization.
Based on an analysis of 17 observational studies, IVIg slightly reduces the risk of death, especially in children [68].
A different analysis that looked at 26 studies found that IVIg + steroids reduce recovery time by about 3 days. This benefit was greatest in Asians. However, IVIg did not reduce the risk of death [69].
Transplant Rejection
A transplanted organ can sometimes be rejected by the recipient’s body. Transplant recipients must take immune-suppressing medications to decrease the risk of rejection.
There are many ways a transplant can be rejected. One process involves an immediate rejection caused by an antibody attack.
IVIg, combined with other medications, may be effective for this type of rejection. One study found a therapy that includes IVIg results in a 91.7% survival rate for kidney transplants after 3 years [70, 71].
Infection-Related Mental Disorders
In rare cases, bacterial infections can cause mental disorders in children. This leads to a variety of behavioral and psychological symptoms, which occur shortly after an infection.
This disorder was discovered fairly recently and is not well understood. It may be caused by the immune system attacking brain cells [72].
There is hope that IVIg may be beneficial as a treatment. A case series of 12 children found that a single dose of IVIg provided lasting symptom improvement [73].
However, a recent clinical trial of 35 children found that IVIg did not perform significantly better than placebo [73].
Overall, research is lacking for this rare disorder and experts are not sure if IVIg should play a role [74, 75].
Hives
Delayed pressure urticaria is a rare form of hives. It causes painful swelling in locations where the skin has experienced sustained pressure. The symptoms are often severe and significantly decrease the quality of life [76].
Steroids are often the only treatment that is effective. However long-term use of steroids comes with many drawbacks [76].
Case reports indicate that IVIg might be beneficial in this form of hives. IVIg improved the symptoms in 5 out of 8 patients who did not respond to other medications [77].
IVIg Side Effects
This list does not cover all possible side effects. Contact your doctor or pharmacist if you notice any other side effects.
Call your doctor for medical advice about side effects. In the US, you may report side effects to the FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch. In Canada, you may report side effects to Health Canada at 1-866-234-2345.
IVIg is generally well tolerated and safe. Approximately 20 – 40% of people experience a mild side effect at some point. The side effects depend on the disease being treated and how IVIg is given [78+].
Injection Site Side Effects
As the name implies, IVIg is primarily given through IV. Side effects can sometimes occur due to needle insertion.
Sometimes a short needle is used to inject IVIg right under the skin. This type of needle causes more injection site side effects, but reduces the number of infusion side effects [78+].
Injection site side effects include [78+]:
- Pain
- Bleeding
- Bruising
- Swelling
- Redness
Infusion Side Effects
Infusion reactions are the most common side effects of IVIg. These side effects occur while IVIg is slowly delivered to the person. Infusion of IVIg typically takes 2 to 4 hours.
Infusion side effects can be prevented or reduced by slowing or stopping the delivery of IVIg. Steroids and Tylenol are also effective at reducing reactions [78+].
Infusion reactions include [78+]:
- Nausea
- Mild fever
- Feeling sick
- Dizziness
- Chest tightness
- Fatigue
- Chills
- Vomiting
Side effects are more likely to occur with [78+]:
- The very first infusion
- A fast infusion
- A large dose
- A long break between infusions
- Switching to a different brand
- Recent bacterial infection
Serious Side Effects
There are cases of IVIg causing moderate to severe side effects in some users. These side effects are usually delayed, occurring days to weeks after infusion [78+].
Severe side effects include [78+]:
- Allergic reaction
- Persistent headaches
- Kidney damage
- Blood clots
- Blood cell abnormalities
- Lung injury
Contamination
Contamination is always a concern for any product created from blood donors. IVIg product quality is monitored and tested, but there are rare cases of infection caused by contamination.
In the early 90s, IVIg was linked to several hepatitis C infections. Since then newer decontamination techniques have been developed and there have been no new cases of infection [79, 80].
IVIg is also linked to cases of parvovirus B19 infection. This virus is not destroyed by the decontamination process. Normally this is not a concern because the antibodies in IVIg should neutralize the virus. Despite this, there have been 2 cases of individuals developing this infection from IVIg [81, 82].
Limitations and Caveats
Research Limitations
IVIg is a potential treatment in a wide variety of disorders. However, many of these diseases are extremely rare, which makes clinical research difficult. Many of the potential uses of IVIg are based on a few case reports [2+].
The dose of IVIg can vary depending on the disease being treated. Research is still trying to determine the optimal dosage for each disease. Efforts are also being made to find the lowest effective dose of IVIg in different conditions to save on cost [83, 2+].
Researchers also do not fully understand how IVIg therapy works. A better understanding of IVIg could improve treatment and recommendations.
Cost
The high cost of IVIg is a significant issue. The yearly cost of IVIg and infusion services can range from about $50,000 to $100,000. For some conditions, individuals must receive IVIg every 3-4 weeks for the rest of their life. This can end up costing millions of dollars [84].
Cost analysis shows that IVIg is not cost effective in many diseases. Evidence suggests that other therapies can often improve the quality of life at a lower cost [85, 86].
Different Brands
There are currently over a dozen IVIg products available. Manufacturers use varying amounts of donors for their IVIg. This can lead to different concentrations of components. The inactive ingredients, pH level, and decontamination methods can also differ between each product [2+].
Switching from one IVIg product to another may require slight adjustments to the dosage. Using a new brand can also potentially cause new or different side effects [78+].
IVIg Drug Interactions
Drug interactions can be dangerous and, in rare cases, even life-threatening. Let your doctor know about all drugs and supplements you are using or considering to reduce the risk of drug interactions.
Kidney Toxicity
Rare cases of kidney failure have been reported with IVIg use. Research shows that kidney injury is more common with brands of IVIg that contain sugar as a preservative. IVIg should be used cautiously when taking other drugs that are toxic to the kidneys [87].
Live Vaccinations
The interaction between IVIg and vaccines has not been studied. However, the antibodies in IVIg can theoretically decrease the effectiveness of live vaccines. The CDC recommends waiting 8 months after taking IVIg before receiving MMR or varicella vaccinations [88].
NSAIDs
One study of 182 children looked at the drug interaction between IVIg and NSAIDs. They found that NSAIDs may have a negative effect on IVIg when treating Kawasaki disease [89].
IVIg Dosage
Dosage Guidelines
IVIg dosage is personalized for each person and disease. The dose, infusion rate, dosage schedule, and duration of treatment can all vary depending on the condition. Researchers are still trying to find the optimal dose for each disease.
The dose of IVIg is based on the weight of the person. Different brands of IVIg may require slightly different doses [2+].
IVIg comes in a liquid form that is given through IV or injected underneath the skin [2+].
FDA approved IVIg doses [90]:
- Primary humoral immunodeficiency – 200 – 800 mg/kg every 3 – 4 weeks
- Immune thrombocytopenic purpura – 1 g/kg for 2 consecutive days
- Chronic inflammatory demyelinating polyneuropathy – 2 g/kg over 2 – 5 days, then 1 g/kg every 3 weeks
Studies suggest that IVIg dosage should be based on maintaining a certain IgG level in the blood. Researchers have found that IgG levels above 700 mg/dL reduce the risk of pneumonia [91, 92].
People with genetic disorders may require IVIg for the rest of their life.
Some infection-related diseases require a single IVIg dose of up to 2 g/kg [73, 52].
In special cases, IVIg can be taken by mouth to fight gut infections. A dose of 300 mg/kg was used in studies [57].
