Fran Lowry

November 21, 2011

November 21, 2011 (Boston, Massachusetts) — A novel immunoglobulin (Ig)G replacement therapy that uses hyaluronidase to facilitate dosing with gammaglobulin has shown good efficacy in preventing infections in people with primary immunodeficiency disease (PIDD), according to a study presented in a poster session here at the American College of Allergy, Asthma & Immunology 2011 Annual Scientific Meeting.

"In addition to reducing the rate of bacterial infections, the study suggests other potentially useful attributes of hyaluronidase plus gammaglobulin, such as the possibility of dosing once a month instead of every week," lead author Mark Stein, MD, from Allergy Associates of the Palm Beaches in North Palm Beach, Florida, told Medscape Medical News.

People with PIDD usually receive gammaglobulin intravenously once a month or subcutaneously once a week. The protective effects of the new combination therapy, which consists of human immunoglobulin and recombinant human hyaluronidase (IGHy), will last 4 times as long as other subcutaneous preparations, Dr. Stein said.

"This technique administers the 2 compounds through the same needle. First hyaluronidase opens up the subcutaneous tissues by breaking the bonds in hyaluron, the substance that fills the subcutaneous space. This allows us to put large volumes of gammaglobulin into that space," he explained.

With the usual treatment, a patient receiving subcutaneous IgG replacement will typically have to inject 20 to 30 mL of fluid in 2 to 4 different locations every week. With the new technique, the patient can inject 300 mL in one spot through one needle all at once, as fast or faster than intravenous (IV) gammaglobulin, Dr. Stein explained.

"A lot of people like intravenous administration because it is given once a month. Being able to do subcutaneous administration once a month is a major advance in terms of offering another approach," he said.

Subcutaneous administration of IGHy also has fewer adverse effects than IV administration.

"One of the disadvantages of giving immune globulin intravenously is that it produces a very high peak level because it goes directly into the bloodstream. We get a lot of systemic side effects, such as headaches," Dr. Stein said. "No matter how you give it, headache is always the biggest side effect, but it's much more frequent with intravenous administration."

Other systemic adverse effects include muscle aches, fatigue, nausea, vomiting, and abdominal upsets. These adverse effects are lessened with subcutaneous administration, Dr. Stein noted.

In their study, Dr. Stein and his colleagues enrolled 87 patients with PIDD in the United States and Canada and treated them with IV IgG once a month for 3 months.

For 12 months, the 83 patients were treated with 75 units of IGHy administered subcutaneously, followed by IgG 10% infused subcutaneously through the same needle, at a dose of 108% of the previously prescribed IV IgG dose, using a variable rate pump.

A total of 1129 IGHy infusions were administered; of these, 94% were administered at the same 3- to 4-week intervals as IV IgG. The mean dose was 616 mg/kg every 4 weeks. Most of the infusions were administered at a single site, and 98% were completed without requiring a change in rate because of drug-related adverse events. They were also given more rapidly than IV infusions.

Systemic adverse events occurred in 8.3% of subcutaneous IGHy infusions (95% confidence interval [CI], 6.3 to 10.0), compared with 25% of IV IgG infusions (95% CI, 16.7 to 25.0).

The most common local adverse reactions were discomfort or pain, erythema, swelling and edema, and pruritus.

Among IGHy-treated patients, serious validated bacterial infections occurred at an annualized rate of 0.025, which is lower than the threshold set by the US Food and Drug Administration of less than 1.0 annually. The annual rate of all infections with IGHy was 2.97, Dr. Stein noted.

He also pointed out that IGHy is bioequivalent to IV IgG at 108% of the IV dose, and that it provided lower peak IgG concentrations, which were similar to weekly subcutaneous IgG administration.

"This method leads to better absorption. The hyaluronidase facilitates the absorption so that the immune globulin gets into the lymphatic system and then the bloodstream more efficiently," Dr. Stein pointed out.

It is estimated that primary immunodeficiency is currently diagnosed in 200,000 people in the United States, but Dr. Stein believes that the actual figure is more than double that. "It's an underdiagnosed condition," he said.

At the end of the 12-month study period, patients asked to remain on IGHy, he added. "They preferred it to the other therapy they had been on, and all wanted to continue, including the parents who had children in the study," he said.

"We want to make replacement therapy as easy and inexpensive as possible. This method is certainly more convenient. Patients don't have to stick themselves with a bunch of needles every week," Dr. Stein said.

Medscape Medical News invited Mark S. Dykewicz, MD, from Wake Forest University School of Medicine, Winston-Salem, North Carolina, to comment on the study.

"Over the past several years, there has been a shift from intravenous to subcutaneous administration for patients with primary immune deficiency disease who need immunoglobulin replacement," said Dr. Dykewicz, who was a comoderator of the oral presentation session.

Subcutaneous administration offers several advantages, but it does require multiple infusions using small caliber needles, he noted.

"This study shows that adding hyaluronidase to immunoglobulin permits the use of a single subcutaneous infusion site, and reduces the amount of immunoglobulin needed to achieve target blood antibody or immunoglobulin levels," Dr. Dykewicz said.

The study was sponsored by Baxter Healthcare Corporation. Dr. Stein has disclosed no relevant financial relationships. Dr. Dykewicz reports financial relationships with Merck and Shire.

American College of Allergy, Asthma & Immunology (ACAAI) 2011 Annual Scientific Meeting: Abstract P268. Presented November 5, 2011.


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