A Comparative Look at IVIG and SCIG

By Kris McFalls and Ronale Tucker Rhodes, MS

Prior to the early 1980s, most patients in need of immune globulin treatments had few options but to endure painful intramuscular injections, causing many to forgo therapy. And, while subcutaneous immune globulin (SCIG) infusions were being performed in the 1970s, they were not approved by the U.S. Food and Drug Administration (FDA), nor were they the norm. So, when intravenous immune globulin (IVIG) was licensed for use in the U.S. in 1981, it provided patients with a much-improved method of receiving their needed medication.

Almost three decades later, IVIG continues to be the primary treatment modality. For some, it is the therapy that works best for them; for others, it comes with complications, such as unwanted side effects and peripheral access problems, as well as the need for more convenient therapy. These issues led medical researchers to look back at the use of SCIG, and in 2006, the FDA approved the first SCIG product: CSL Behring’s Vivaglobin.

But Vivaglobin is not the right product for every patient who requires IG infusions. As a result, many patients currently infuse other IG products subcutaneously, despite the fact that the FDA has not given approval for that method of treatment. Knowing this, other manufacturers are testing new IG products for subcutaneous use. On the horizon are Baxter’s Gammagard Liquid with recombinant human hyaluronidase currently in Phase III clinical trials, and Talecris’ Gamunex awaiting FDA approval for a subcutaneous indication. Despite the product of choice, the question is whether SCIG or IVIG is best for patients, and that depends on many factors.

Cost of Product and Treatment

No significant differences in cost between SCIG and IVIG products exist either for the patient or insurer. However, there are different cost considerations related to the site of care, including nursing and supplies.

The primary cost difference between the two types of treatment centers on supervision. During IVIG infusions, medical supervision is required, whereas it is not for SCIG patients who self-infuse and incur no infusion nursing costs. Even for IVIG patients, the cost to infuse at home is less than at a healthcare site. As a result, some insurance companies are encouraging both IVIG and SCIG patients to infuse at home rather than in a clinical setting. The exception to this is HMOs. Previously, HMOs had no outside costs for medical supervision in the clinical setting, so these organizations initially did not allow the transition to SCIG. But thisis changing, and some HMOs are now starting to allow their patients to switch to SCIG.

Many IVIG patients prefer home treatment because it’s more convenient for them since it cuts down on the cost and time of traveling to a clinical setting. While Medicare Part B will pay forIVIG preparation in the home—but only for primary immune deficiency (PIDD) patients — it will not pay for nursing or supplies in the home unless the patient is certified as homebound. On the other hand, IVIG in the home can be covered under Medicare Part D for indications other than PIDD, but again, supplies and nursing are not covered. In this situation, IVIG reimbursement is typically higher, so some homecare companies will often bundle the cost of nursing with the cost of the IVIG product if the reimbursement rate is high enough. In addition, many HMOs don’t allow for IVIG home therapy because they are not set up to accommodate it, and as was previously noted, there are no outside costs for medical supervision in the clinical setting.

Overall, SCIG therapy in the home setting has a more favorable reimbursement rate than IVIG therapy. And, Medicare covers SCIG under the durable medical equipment (DME) benefit because, under the FDA approval, SCIG requires the use of a mechanical pump.

Comparing the Site of Care

Protocol requires that all patients receive at least their first infusion in a clinical setting, whether infusing subcutaneously or intravenously.After that, SCIG patients can treat themselves in the privacy of their homes, which offers convenience, autonomy and flexibility not found in the clinical setting.IVIG patients also have a choice. They can be treated in a clinic, hospital, outpatient infusion clinic and even in their home.

However, because IVIG requires monitoring by either an infusion nurse or doctor, these choices may be limited for some. Many patients can be infused safely at home, while others and their doctors may prefer the higher level of safety in a hospital or clinical setting — especially for patients at high risk of anaphylactic reaction or other issues such as myocardial infarction, brittle asthma, renal disease, etc., says Dr. Terry Harville, medical director at the Special Immunology Laboratory at the University of Arkansas for Medical Sciences. In addition, some patients have autoimmune conditions that require higher IVIG dosings than can be delivered subcutaneously, thus necessitating IVIG in a clinical setting.

Clinical infusions allow doctors and/or nurses to interact with patients on a monthly basis and provide a higher level of supervision for monitoring patients’ overall health and response to treatment, which may be required for patients who are more likely to be noncompliant with therapy. For instance, many patients are so adept at living with chronic disease that they become anesthetized to symptoms that may be precursors of increased disease state or of oncoming infection. This desensitization, then, causes patients to sometimes fail to be good historians of their disease process, which can lead to less-than-optimal treatment. However, experienced infusion nurses who have monthly contact with patients can quickly spot subtle changes in patients’ health. In turn, these nurses become skilled at asking questions that help the patients become better historians of their health status.

And while homecare offers many advantages to patients, there are other reasons why it may not be the best treatment or the treatment of choice. Compliance and the ability to perform SCIG treatments can be a concern, especially for younger individuals. And, there are those who prefer to keep their home a home — without the medical equipment as constant reminders of their disease. Many patients also prefer letting someone else take care of them for a while and like the comfort and safety they experience in a clinical setting.

Frequency of Treatment

Another distinction between the two treatments is the frequency of infusions. Typically, IVIG patients receive infusions every two to four weeks, whereas SCIG patients infuse every week. In fact, some SCIG patients are opting to infuse even more frequently. For instance, some doctors recommend patients give themselves one small daily injection instead of a single larger weekly infusion. Daily infusions are given by push, rather than with a pump. According to Dr. Hans Ochs, professor of pediatrics at the University of Washington, and a doctor at the Center for Immunity and Immunotherapies at Seattle Children’s Research Institute, “Some adults dislike infusing with a pump and the infusion of large amounts of IG subcutaneously, but rather prefer to inject 10 to 12 mL [5 to 6 mL per site] daily, up to seven times per week. The advantage of giving IG by push several times a week is the simplicity of the procedures and the little time it takes [5 minutes or less].”

The frequency of IG treatments affects how patients feel, evidenced by their peak and trough levels. The level of IG in the bloodstream immediately after an infusion is known as the peak level; the level of IG right before the patient’s next infusion is known as the trough level. Since IVIG patients receive fewer infusions spaced farther apart, they often experience increased lethargy due to low trough levels just prior to their scheduled infusion. In contrast, SCIG patients who have smaller and more frequent infusions experience higher and more stable trough levels with less variation between peak and trough.(See Figures 1A, B and C.) “There is very little change in IgG levels between the weekly infusions,” explains Dr. Ochs. And, “there should be no fluctuation at all if the infusions are given several times a week.”

In a 2003 survey by the Immune Deficiency Foundation, 68 percent of respondents indicated that they “usually” or “sometimes” could feel their IVIG “wearing off” before their next infusion was due. “The cause of this is not clear, but many doctors suspect this is due to increased symptoms from chronic infection [which may not otherwise be clinically apparent] and/or new infections occurring as the patient’s IgG level drops,” says Dr. Melvin Berger, division chief of allergy and immunology at University Hospitals Case Medical Center, and adjunct professor at Case Western Reserve University. “IgG in serum, no matter how it is infused, has an average half-life of about 22 days. This means that some people have shorter half-lives — their IgG gets used up by the body faster or is lost from the body via the kidneys or GI tract.” Berger recommends that if patients experience an increased incidence of infections or increased symptoms near the time their next infusion is due, they discuss this with their doctor to determine whether their infusions should be given closer together and/or whether their dose should be increased.

“IgG given subcutaneously has the same half-life in the body as IgG given intraveneously, but it reaches its peak concentration more slowly — usually two to three days after it is given. In contrast, after an IV infusion, the peak is reached immediately,” explains Berger. And, since in most subcutaneous treatment regimens, the next dose is given much sooner — often weekly or even twice a week or daily — the IgG is being replaced as soon as it is metabolized by the body, so the serum IgG level remains much more constant. “Several studies have documented that with subcutaneous infusions once a week, the serum IgG levels achieve nearly a true ‘steady state,’ eliminating many of the symptoms associated with the peaks and troughs of monthly IV infusions.”

Safety Considerations

Regardless of whether patients are being treated with IVIG or SCIG, the risk of contaminated products is the same. All IG products must meet certain criteria established by the FDA for purity and safety. Yet, because IG is derived from human plasma, risk of potentially infectious agents cannot be totally eliminated. In the U.S., however, there has never been a documented case of HIV transmitted in IG.

IVIG patients, though, have a higher risk of thrombosis because infusion is administered through the vein. The risk is further heightened by a health history of diabetes, renal dysfunction, age (65 and older), coronary artery disease, hypertension, cerebrovascular disease, hyperviscosity disorder (including multiple myeloma, macroglobulinemia and polycythemia), thrombotic events and peripheral vascular disease. In addition, any patient who has had a vascular or cardiac episode while receiving IVIG should be infused in a monitored setting. And, whenever a patient experiences an adverse reaction to IVIG, a new consent form must be completed.

Side Effects

Both IVIG and SCIG can cause manageable side effects, including headache, chills, nausea and flu-like symptoms. However, side effects do appear to be less severe for SCIG patients. Because SCIG is absorbed by the body more slowly through the fat tissue, instead of in large doses entered directly into the circulatory system, it is believed that SCIG causes milder systemic reactions than IVIG.

SCIG comes with site reactions, too, which usually decrease over time. These include mild-to-moderate swelling, itching, redness and tenderness at injection sites.

A Patient-by-Patient Decision

The inherent differences between IVIG and SCIG treatment modalities are significant. The determination to prescribe one over the other depends on each patient’s unique situation, including their medical history, response to treatment, compliance with therapy and lifestyle. But, in general, Harville explains that “patients with difficult or more complicated disease would probably be better served in a clinical setting where an evaluation is performed with each monthly infusion. Patients with well-controlled disease capable of self-administration should probably be offered SCIG treatment at home.”

KRIS MCFALLS is the full-time patient advocate for IG Living magazine, written for patients who depend upon immune globulin products and their healthcare providers, and RONALE TUCKER RHODES, MS, is the editor of BioSupply Trends Quarterly magazine.

Editor’s Note: IG and IgG are common abbreviations with identical meaning, both referring to immune globulin.