Immunoglobulin therapy FAQs

Unfortunately, we cannot give you a definite answer. Your immunology team will help ensure long-term patients are kept for as long as possible on a particular product. However, there are factors beyond their control that might come into play. These include problems of supply of your particular product e.g. any unforeseen batch contamination issues or production problems, the brand being withdrawn by the company or healthcare commissioners deciding that they are only willing to procure cheaper alternatives. Please see our leaflet on switching immunoglobulin products.  

Your immunology team will give you contact details which you can use if a problem arises at home; for example, if you think you have an infection and you want advice about delaying immunoglobulin treatment. Some immunology centres offer this service during office hours only. This means you might want to plan your infusions for during the week until you have some confidence. You can also call your immunology centre if you have other concerns that might be to do with immune deficiency.

Your immunology team will be accredited as a home therapy training centre and will not allow you to go onto home therapy until you are safe. You might have to do a short exam! Once you are on immunoglobulin at home, your team will want to do an assessment every so often. Your assessment will happen either at home, or at the hospital.

Being on immunoglobulin should not affect your holidays. If you are on IVIG, a holiday of up to three weeks could be fitted into your infusion schedule. If you are on weekly SCIG, you will either need to take an infusion with you or have a bigger dose in the weeks before and after your holiday. Your immunology team will help you plan this.

In the past, supplies of immunoglobulin from different manufacturers have been withdrawn from time to time. This has happened because, for example, a batch of immunoglobulin has caused a reaction, such as an itchy rash. Another problem is that immunoglobulin is being used to treat many more different diseases, not just immune deficiency. Immunoglobulin costs more in some countries, so manufacturers make a greater profit in different parts of the world.

In the past, there have been occasions when supplies of an immunoglobulin product became very low. People on an affected product had to switch to a different one at very short notice.

For these reasons, the UK Government has taken steps to ensure we have a good supply of immunoglobulin at a national level. These steps include negotiating immunoglobulin prices and supplies with the manufacturer. The Department of Health also runs a scheme to make sure that if a crisis develops, immunoglobulin is reserved for patients who really need it, particularly people with immune deficiency.

There are about half a dozen immunoglobulin manufacturers and the different IVIG and SCIG products available vary slightly. However, each manufacturer must follow international standards on product safety. The blood donor centres and manufacturing plants of all the different companies are inspected from time to time.

The tests you had before starting immunoglobulin were designed to check whether you would need immunoglobulin for life. However, sometimes immunoglobulin is recommended for people whose immune deficiency may only be temporary. This can happen in small babies or when the immune system had been damaged by medications, for example. It’s also possible you were given immunoglobulin for a condition that is no longer regarded as needing immunoglobulin. In these situations, there are blood tests that can be done to check how well your immune system is working. If you do stop immunoglobulin, your immunology team will monitor you closely.

Immunoglobulin is manufactured in batches. Several thousand donations of plasma are pooled in each batch. Very occasionally there are problems with some batches. For example, recently one batch of immunoglobulin caused some people to get an itchy rash. Because it was possible to see which batch was causing the rash, replacement immunoglobulin could be sent out quickly.

The exact protocol for follow-up varies between centres and will also vary depending on your particular situation. You could expect to be seen at least two or three times a year. Sometimes follow-up will be done by a specialist trainee doctor or a specially trained nurse if it is a recognised teaching centre. You might be asked to bring along the details of your infusions, including the number of batches and possibly a diary of any infections you have had.

You might expect to be assessed from the following points of view:

• Is the treatment working?
• Are you still having infections?
• Have you had to have antibiotics, take days off work or even go into hospital?
• Are you getting the correct amount of immunoglobulin (checked by doing a blood test)?
• Are your lungs healthy? You might have breathing tests or a CT scan of your lungs.
• Are there any problems?
• Have you had any reactions? What caused them?

A blood sample may be taken for liver tests and a sample frozen in case it needs testing for infection at a later date.

You might be offered a technique review if you are on home therapy.

• Has anything else changed?
• Have you had any other complications of immune deficiency?
• Are there any new treatments or tests that should be considered?
• Do you still understand why you are on immunoglobulin and what the possible risks are?

At monitoring visits, a huge amount of information will be swapped between you and the immunology team. This can be slightly stressful and it’s possible you won’t remember everything that has been said. You might want to prepare for the monitoring appointment by checking you have your infusion records and infection diary. A lot of people jot down any questions they think of in the days leading up to the appointment. You might want to take someone along to the appointment to remember what has been said, or you might just want to take notes.

The first step the manufacturers take is to get to know the blood donors really well. Manufacturers insist that their donors donate regularly. Each time a donor attends the blood centre they are asked a lot of questions, ranging from their sex lives to any recent travel. They then donate the blood as well as having a series of blood tests to make sure they don’t have an infection. The blood is not released for processing until the blood tests have come back negative.

The second step is that the plasma is treated in a few different ways to get rid of infection. Depending on the manufacturer, the plasma will get a combination of heat treatment (pasteurisation), addition of solvent detergent, and nano-filtration with or without UV light treatment.

Donor centres and immunoglobulin manufacturers have very high standards for minimising the risk of infection getting into the immunoglobulin supply. Donor centres and manufacturers are inspected regularly and will be closed down if there is any hint of a problem.

A final important safety step is carried out by immunologists, who either do annual hepatitis checks or save a sample of blood for infection testing. You will also be kept on the same immunoglobulin product once you have started. It is through this kind of surveillance that we can be so confident that immunoglobulin and its administration is as safe as possible.

Immunoglobulin is made from blood donations. Several thousand blood donations are pooled in the process. For these reasons there is always a possibility of catching an infection from one of the blood donors.

No one has ever caught HIV or hepatitis B from immunoglobulin therapy. In the 1990s, a small number of people caught hepatitis C from immunoglobulin. These days, blood donors are selected very carefully and the manufacturing process contains steps to remove viruses and bacteria.

There have been no cases of infection being spread from person to person by immunoglobulin since the 1990s.

There are two theoretical risks from immunoglobulin. The first is from prion infection. Prions cause BSE (mad cow disease) and variant CJD, mainly in the UK. Prions have been spread from person to person by blood transfusions but never by immunoglobulin.

The other risk is of new infections that start to affect humans, either because of global climate change or change in behaviour (e.g. feeding sheep to cows, in the case of BSE). One example of this is a virus that affected people in New York and entered the blood supply there.

It is very difficult to predict whether new infections, which could be spread by immunoglobulin, will appear in the future. However, the immunoglobulin manufacturers and immunologists around the world are constantly on the look out for any problems such as this.

Most people do not have reactions to immunoglobulins. This is why it is safe to go on to home therapy.

The reactions that do sometimes happen include rashes, temperature, shivering or itching. You can also get a headache with immunoglobulin, although this tends to happen the next day.

When reactions do happen, there is usually one of two factors responsible:

• Immunoglobulin is given too fast for the individual concerned. This is most likely to happen with IVIG because a larger dose is being given. If you have a reaction during an infusion, the first thing to do is slow the infusion right down and consider stopping it if the symptoms do not improve rapidly. Once recovered, you should record the details of the reaction in order to inform your clinical immunology team.
• Immunoglobulin is given at a time when there is an infection. If you have a cold or a chest infection on the day of your infusion, you are more likely to have a reaction. Immunology teams will help you recognise the symptoms of infection, so that you can delay your infusion by a couple of days if necessary. Because immunoglobulin treatment takes a few months to reduce the risk of infections, this is most likely to happen when you have just started immunoglobulin.

If you continue to have reactions with immunoglobulin, your immunologist may recommend taking paracetamol or antihistamines first. Sometimes reactiions occur with one batch of immunoglobulin but these may go away once the batch has changed. Very occasionally your immunologist will recommend you change your immunoglobulin product because reactions cannot be brought under control.

If you have reactions when you start immunoglobulin treatment, the chances are that they will be brought under control.

Your immunologist will only recommend starting immunoglobulin if you have had tests which confirm it is the right treatment for you. In cases of severe immune deficiency, only a couple of blood tests are required before the doctor will recommend immunoglobulin.

Fortunately, most people have mild immune deficiency and in this situation the doctor might try other treatments before immunoglobulin. For example, the immunologist might try giving you vaccines and checking how well you respond. This ‘vaccine challenge’ can take several weeks, as you have to have the vaccine, wait a few weeks before the blood tests and then get the results.

Your immunologist might suggest taking regular antibiotics for a few months and seeing how well these protect you from infection. This can be done whilst you are waiting the results of a vaccine challenge.

Finally, your immunologist might suggest trying immunoglobulin for a period of time, for example a year. If it is clear that you have benefitted, then they will recommend you continue it, but if you do not benefit your immunologist will suggest stopping.

Immune deficient patients are at a greater risk of infection than others. Clinical trials have shown that for people with immune deficiency, immunoglobulin treatments result in fewer infections, and those infections that do occur tend to be less serious. There is also evidence that people with immune deficiency are more likely to enjoy good health over many years if they receive immunoglobulin correctly. Finally, your wellbeing and your energy levels are likely to be better if you are on immunoglobulin. Please note that it may take several months before you feel these benefits.

Immunoglobulin is made from donated blood plasma. During manufacture everything except a type of immunoglobulin called IgG is removed from the plasma. IgG is very good at fighting bacteria and viruses. IgG has other effects too, so it isn’t just used for people with immune deficiency. You might hear about immunoglobulin being used in some people with other immune (autoimmune) problems.

Your immunology team will give you the information to help you decide which treatment you will have. You might want to consider the following factors:

• If you have really ‘bad’ veins, then IVIG is not be your best option
• If you want to take ownership of your illness, then SCIG may be the best choice because you will probably learn how to have home therapy faster.
• Infusion-related side-effects are more common with IVIG than SCIG and can be related to the volume and rate of infusion.

Your immunology centre will be able to offer you either treatment depending on these factors and your personal choice. Across the UK about 30-40 per cent of people with immune deficiency are on IVIG.

Intravenous immunoglobulin (IVIG) has been in use since the 1970s and involves giving immunoglobulin straight into the circulation system by a needle in a vein. Quite large amounts of immunoglobulin can be given this way and for this reason, treatment is only needed every three weeks or so, with each treatment lasting between two and four hours. If you have side effects with IVIG it is usually because it is being given too quickly. Initially you would have treatment in hospital, but most people can be trained to have it at home.

Subcutaneous immunoglobulin (SCIG) has been developed more recently than IVIG, with new immunoglobulin preparations being produced extensively for subcutaneous use by 2005. In SCIG, immunoglobulin is delivered by a needle into the fatty tissues under the skin, where it enters the circulation slowly over a few days. There isn’t much room under the skin, so the dose of immunoglobulin given is smaller than with IVIG. For this reason, SCIG is usually given every week. Nearly everybody on SCIG learns how to have treatment at home, with each session lasting up to about two hours.

Immunoglobulin (IG) replacement therapy is a blood-based treatment. The immunoglobulin contains antibodies which will help fight infection. You have been recommended this treatment because your doctors have found that your immune system (or your child’s immune system) is not making antibodies. Immunoglobulin can be given intravenously or subcutaneously.

No you don’t have to go hospital if you don’t want to. You can be trained to do it at home by your nursing team. This may seem daunting at first but lots of people do it this way and find it very convenient. 

Yes – they may be related to the dose and route (e.g. very high doses intravenously can cause renal impairment), also some batches do not suit some people and a variety of side effects can occur (headaches, joint pain, local swelling and itching for subcut) which should be explained by the team before starting. 

Doctors will look at how often you have an infection (infection frequency) and the levels of immunoglobulin in your blood just before an infusion, to make sure its adequate (trough level).  It’s a good idea to keep a diary of any infections you have. This will help your doctors and nurses understand how your immunoglobulin treatment is working. 

The development of keloid is usually related to wound healing from incisional scars (due to surgery) rather than the infusion of a liquid into the subcutaneous space.  Some individuals will rarely get fibrosis (excess fibrous connective tissue), but not usually keloid at sites of infusion.  The fibrosis is where the connective tissue becomes thickened and is apparent as a nodule under the skin at the site of infusion. 

Itching at the site of injection is common.  Whether or not to treat this problem depends on the severity. If it is minor and lasts a few hours it may not be necessary to do anything.  For some people antihistamines work, topically (skin) applied steroids have been tried prior to the injection at the injection site, but there is limited evidence that it works.  For some people, it is a reaction to the plastic surrounding the needle or any dressing applied and changing these may help.  Finally if very problematic you may need to discuss switching products, since it may be one of the stabilizing agents that you react to. Do report any problems to your health team. 

There are a number of studies that have looked at the use of intravenous immunoglobulin therapy in Alzheimer Disease and there is no evidence of benefit. There are some rarer infections of the central nervous system, associated with loss of higher or cognitive function and good immunoglobulin treatment prevents these infections from taking hold. 

Veins can usually recover in the 3-week gap. If your veins do become brittle then your immunology team might recommend changing to another way of giving immunoglobulin such as subcutaneous infusion.

The risk of transmissible infection is as low as possible with an appropriate screening of donors and donor pools of plasma before they are manufactured into Ig, but the risk isn’t zero. Plasma is treated in a few different ways to get rid of the infection. Depending on the manufacturer, the plasma will get a combination of heat treatment, the addition of acid or detergent, and filtration. All steps are taken to ensure the product is as safe as possible. 

Some patients have conditions that improve over time e.g. secondary antibody deficiency, in such cases taking someone off immunoglobulin to see if their own immunity is improved can be a very positive step. 

Immunoglobulin costs £40-65 per gram so a typical replacement dose is about £2300 on top of which there will also be administration charges and a day care fee. You would need to see a private doctor to discuss this with them. 

In some UK centres and parts of Europe patients with secondary antibody deficiency only have their IgG over the higher risk winter months and then have 6 months off.  The choice to do this must be based on full knowledge of the patient history.

The half- life of IgG is 17-21 days, so it takes about 3 weeks to fall by half from the level achieved on the day of infusion.  It is generally thought that 12 weeks are needed for all of an infused dose of IgG to disappear from the system, but that varies from individual to individual.

A choice will have been made based primarily on the route of administration of the product, either intravenous, (through your veins) or subcutaneous (through your skin) and the availability of that product in your area. The source plasma is the sa me, and most products are “fractionated” (separated out from) plasma by the same methods and have the same viral inactivation and safety steps. The key differences are often in the stabilizing agents (sugars or proteins) and concentration (which affects infusion times). Some individuals may react to a given product or batch, but this rarely requires a product change.

Ig replacement therapy should protect against the common circulating bacteria and viruses but some common viral infections do not generate good lasting protective antibodies or these are not helpful in preventing recurrence, for example of the common cold. Patients with underlying lung, ear or sinus disease (e.g. bronchiectasis) may still get infection from infectious reservoirs in those tissues.  Occasionally trough Ig levels dip for a variety of reasons. If the infections are needing further antibiotic therapy this should be discussed with your immunology team.

The beneficial effects of immunoglobulin therapy may take up to 12 weeks, to achieve steady trough levels, but many people notice fewer infections sooner.  Some patients are disappointed when features such as fatigue persist despite fewer infections and good trough levels, but this is not unusual.

It is never advisable to infuse whilst you are ill. The best course of action is to speak to your Immunology team.

Some patients have conditions that improve over time e.g secondary antibody deficiency, in such cases taking someone off immunoglobulin to see if their own immunity is improved can be a very positive step.

In general there is no contraindication between having immunoglobulin therapy and killed vaccines, but if the two are given close together and there are high levels of antibody in the Ig to the vaccine then the efficacy is likely to be impaired. Please check with your immunology team about the appropriate timing.

Where possible infusions once started should be completed without interruption. For unavoidable emergencies, we suggest disconnecting the needles and disposing of them and placing the caps on the syringes so the immunoglobulin is stored safely and hygienically. When you restart the infusion use fresh new needles for your infusion. If the break in infusion is any significant time (i.e. more than 30 mins) there is a risk that the product will be contaminated and should be discarded.

You should carry your immunoglobulin in your hand luggage and take it into the cabin with you.  It is recommended not to put immunoglobulin product in the hold because the hold’s temperature will cause it to freeze and this will affect its effectiveness.

It is normal for someone to suffer from fatigue after an infusion, especially if they are newly diagnosed. This feeling of tiredness should stop once their immunoglobulin levels are stable and they have been receiving treatment for a while.

Unfortunately we cannot give you a definite answer. Your immunology team will help ensure long-term patients are kept for as long as possible on a particular product. However there are factors beyond their control that might come into play. These include problems of supply of your particular product e.g. any unforeseen batch contamination issues or production problems, the brand being withdrawn by the company or healthcare commissioners deciding that they are only willing to procure cheaper alternatives.

The decision not to put you back on immunoglobulin (IG) will not have been made solely by your consultant but your case will have been discussed by the entire clinical immunology team before a decision was reached. It would be worth talking further to your consultant to discuss other treatments options such as prophylactic antibiotics which you can read about on our website. If you need IG infusions you will never be prevented from receiving this treatment because of cost. As more and more research is conducted into Immune-deficiencies your diagnosis may change which is why these reviews take place

Take a look at this website page which has travel tips and our ‘Going on Holiday’ leaflet for some travelling trips. Travelling abroad with Immunoglobulin should be fine but please check the customs website of the country you are travelling to make sure.

Most patients with a PID who infuse in hospitals do so in open bays on a ward safely.  Please do discuss your concerns with your immunology team. You may also want to explore alternative ways of having immunoglobulin therapy, such as subcutaneous delivery, as this could potentially lead to home therapy options.