With proper medical care and treatment, many patients with primary immunodeficiency (PI) diseases are able to live healthy and independent lives. Immunoglobulin Replacement Therapy (IgRT) treats PI diseases involving the humoral system, in other words, those characterized by a lack of and/or impaired antibody function.
The term “immunoglobulin” refers to the fraction of blood plasma that contains immunoglobulins, or antibodies. These immunoglobulins (Ig) in the serum or plasma are IgG, IgM, IgA, IgD and IgE. Individuals who are unable to produce adequate amounts of Ig or antibodies, such as patients with XLA, CVID, Hyper-IgM Syndromes, Wiskott Aldrich Syndrome or other forms of antibody deficiency may benefit from replacement therapy with Ig.
Ig is prepared from the plasma collected from a large number of donors, usually between 10,000-50,000, who have been carefully screened to make sure they are healthy and do not harbor certain infectious diseases. The plasma contains a broad range of specific antibodies to many different types of bacteria and viruses. Each plasma donor must be acceptable as a blood donor according to the strict rules enforced by the American Association of Blood Banks and the U.S. Food and Drug Administration (FDA). Donors are screened for travel or behavior that might increase the risk of acquiring an infectious disease. Only the IgG is purified from the pooled plasma. To commercially prepare the Ig for patients with PI diseases, the immunoglobulin must first be purified (extracted) from the plasma. The result is called an Ig infusion. All Ig licensed in the U.S. is made from plasma collected in the U.S.
Purified Ig has been used for more than 50 years and has an excellent safety record. During the purification process and with the final product, there are several steps that destroy or remove many types of viruses, including HIV, to help ensure that the final Ig product does not transmit any known infectious diseases to the patient. Thus, the final Ig product contains highly purified plasma IgG that has a broad range of specific antibodies to many types of bacteria and viruses. It is also effective in helping the white cells in the body kill bacteria, viruses and other germs that may be in the tissues or blood of the patient being treated, and is safe to administer.Back to top
It is important to understand that the Ig that is given partly replaces what the body should be making, but it does not stimulate the patient’s own immune system to make more Ig. It is therefore usually necessary to continue IgRT for the patient’s lifetime. In addition, the Ig only provides temporary protection. Most antibodies, whether produced by the patient’s own immune system or given in the form of IgRT, are used up or “metabolized” by the body and must be constantly replenished. Approximately half of the infused antibodies are metabolized over three to four weeks, so repeat doses of Ig are required at regular intervals.
IgRT infusions are administered in two ways: subcutaneously, meaning under the skin (SCIg), or intravenously, meaning directly into a vein (IVIg). For the most part, both SCIg and IVIg products are equivalent in antibody activity. However, there are some differences that may make one particular preparation more suitable than another for a given individual.
The choice of route of administration of Ig therapy (SCIg or IVIg) should be a decision based on discussions between the patient and provider. This decision is usually based on a number of factors including the clinical characteristics of each patient, the patient’s preferences for therapy, appropriate site of care (home, hospital, infusion center), and sometimes, even insurance coverage.
Before starting Ig replacement therapy, it is important that your provider complete all the immune studies to demonstrate that your immunoglobulins are not only low but that you do not make the specific antibodies that normally respond to natural infections or immunization with vaccines. Insurance companies often review this information before approving IgRT.Back to top
SCIg infusions may be given as often as daily, weekly, or as infrequently as every three to four weeks, depending on the specific SCIg product that is being prescribed, the patient’s age and the preferences of the patient and the prescriber. SCIg is injected relatively slowly, directly under the skin. Because small amounts of Ig are given (often) more frequently and because the Ig is absorbed more slowly, SCIg patients experience a more steady level of Ig in their system over time. Although some patients mention feeling a “wear off” toward the end of the dosage cycle, the “peak” and “trough” associated with IVIg is very blunted or even eliminated entirely when receiving SCIg. Therefore, patients who have side effects from high peaks of IgG or feel “washed out” or weak before their next IVIg dose is due may prefer SCIg. Likewise, SCIg therapy may be an alternative for those patients who have difficulty getting venous access and/or who have systemic adverse reactions to IVIg.
Collaborating with their healthcare provider, SCIg patients have the flexibility to develop a dosing regime that is tailored to their lifestyle. The number of infusions per week or month, when and where the infusions are done, the number of needles used, using an infusion pump or manually pushing the drug, and the rate of infusion are all variables that can be considered to design an individual patient’s SCIg regimen. In addition, one of the most appreciated aspects of SCIg therapy is that it can be self-administered, at home or while on the road, providing increased freedom and flexibility to PI patients. Self-infusing patients must be committed to this therapy and should not “skip” doses or change their regimen without consulting their provider.Back to top
IVIg infusions are usually given every three or four weeks. Most patients tolerate IVIg very well. Infusions are normally administered either in an outpatient clinic or medical facility, although after tolerability and safety is demonstrated in a controlled setting, in rare occasions infusions may be administered the patient’s own home. A typical IVIg infusion will take two to four hours from start to finish. Some patients may tolerate more rapid infusion while others may require longer times. Use of intravenous products allow physicians to give larger doses of Ig at one time than could be given subcutaneously. In fact, doses can be given that are large enough to keep the IgG levels in the patient’s serum in the protective range, even just before the next infusion when the level would be lowest.
Since IVIg infusions are given directly into a vein, they are absorbed relatively rapidly. There is a very high “peak” IgG level in the blood right after the dose is given and a lower IgG level in the blood at the “trough” just before the next dose is due. Some patients feel low energy or “washed out” as the Ig levels in their system reach their low point.
There is a potential for some side effects associated with IVIg. These can include irritation at point of infusion, low-grade fever, aching muscles or joints or, commonly, post-infusion headaches. These symptoms can usually be alleviated or eliminated by infusing the immunoglobulin at a slower rate and/or by giving acetaminophen, non-steroidal anti-inflammatory drugs like ibuprofen, or even small amounts of short-acting systemic steroids. Sometimes saline infusions may be given before IVIg, and/or infusions may be run more slowly to help minimize side effects. Less often, patients experience hives, chest tightness or wheezing. These symptoms usually respond to antihistamines such as diphenhydramine (Benadryl™) and/or asthma medications like albuterol.Back to top
The page contains general medical information that cannot safely be applied to any individual case. Medical knowledge and practice can change rapidly. Therefore, this page should not be used as a substitute for professional medical advice.
This page is not specific to cutaquig®. Please see Indications and Important Safety Information for cutaquig. Please see full Prescribing Information for cutaquig.
1. Kobayashi RH, Gupta S, Melamed I, et al. Clinical Efficacy, Safety and Tolerability of a New Subcutaneous Immunoglobulin 16.5% (octanorm [cutaquig]) in the Treatment of Patients with Primary Immunodeficiencies. Frontiers in Immunology. February 2019, Volume 10, Article 40.
The remaining information included on this page has been excerpted from materials created by the Immune Deficiency Foundation: