Hope for hard-to-match kidney patients

The first (unsuccessful) human-to-human kidney transplant took place 75 years ago.  Some 16 years later, the first successful human transplant took place. Now, according to the United Network for Organ Sharing (UNOS), there are currently 111,714 people in the US awaiting organ transplantation.  Approximately 20,000 of these are so called “hard-to-match” kidney transplant patients.

In other words, their immune systems will reject most kidneys because of antibodies circulating in their blood that react to proteins known as human leukocyte antigens (HLA). These proteins are found on most cells and are used by the immune system to recognize what is foreign to the body.

In HLA-sensitized patients, the body has been exposed to foreign HLA in the past, either through pregnancy, blood transfusion or previous kidney transplant. As such, it immediately recognizes most donor organs as unfamiliar. And, unless these antibodies can be removed, they will result in severe antibody mediated rejection (AMR) and early loss of the transplanted organ.

Apart from the scarcity of donor kidneys, the biggest barrier to kidney transplant is the percentage (nearly 1:3) of patients on the waiting list whose immune systems make them likely to reject most kidneys available to them. Highly HLA-sensitized patients are very difficult to match with less than 7% receiving transplants each year.

SRxA’s Word on Health was therefore interested to hear of a new study from Johns Hopkins which showed that desensitizing such patients with a combination of therapeutic plasmapheresis and intravenous immunoglobulin (IVIG) doubled their chance of survival eight years after transplant surgery, as compared with those who stay on dialysis awaiting compatible organs.

Additionally, the protocol enabled a dramatic 98% transplant rate rather than the traditional 7%.

The results of this study should be a game changer for health care decision makers, including insurance companies, Medicare and transplant centers,” said lead investigator Robert A. Montgomery, M.D., D. Phil. “There’s a dramatic survival benefit, so people should take note. If this were a cancer drug that doubled chances of survival, people would be lined up out the door to get it. It’s really extraordinary to go from 30 percent survival to 80 percent survival after eight years.”

Widespread use of the pre-surgery protocol developed at Johns Hopkins could potentially lead to 3,000 more kidney transplants from living donors each year. The protocol uses plasmapheresis to remove the HLA from the blood before the transplant, then the patient receives low-dose intravenous immune globulin (a human plasma protein) to replace the problematic antibodies and prevent their return. This process is performed every other day for several days before transplant and then for up to 10 days following the surgery.

Although the protocol has great benefit in living donor transplants, it cannot be used in patients receiving cadaver organs – where time is of the essence,  because several days of plasmapheresis and IVIG are needed before surgery can take place.

Additionally, the patient will still to take the same anti-rejection drugs as all other organ transplantation patients.

The desensitization protocol also makes kidney transplants more expensive, However, the cost savings when compared to remaining on dialysis are enormous. Better still, the patient no longer has to endure the difficulties of dialysis, a process that takes about five hours a day, three days a week, and which often makes the tasks of daily life from working to caring for children nearly impossible.

“This treatment increases survival, ensures a better lifestyle and saves the health care system money,” says Montgomery. “There aren’t many things like that.”

Let’s hope healthcare insurers are reading this and taking note.

Bursting the Bubble!

For many Americans, their only knowledge of Primary Immune Deficiency (PID) disease is the much maligned movie Bubble Boy.  The film was inspired by the true story of David Vetter who suffered from the rare genetic disease severe combined immune deficiency syndrome (SCID). Because of his inability to fight infections, David spent most of his short life living in a series of sterile bubbles.

However, the reality of PID is very different.  First off, it’s not one disease. The World Health Organization recognizes over 150 different forms of PID. Some, such as selective IgA deficiency, are not even that rare, affecting as many as 1:500 of the population.  Furthermore, today, if a baby like David receives a bone marrow transplant within the first 3.5 months of life, the survival rate can be as high as 94 percent.  For many of the other PID diseases, patients can live healthy and productive lives with the help of replacement immune globulin therapy.

Produced from the plasma of thousands of healthy donors, immunoglobulin, is a concentrated mixture of antibodies that provides the patient with an “artificial immune system.”  When first developed in the 1950’s, the treatment was administered by painful intramuscular injections (IMIG).

In the 1970’s, the first intravenous immunoglobulin (IVIG) preparations were developed. These quickly became the standard of therapy, as they were more effective, reducing both the need for antibiotics and hospitalizations for infections.  However, the required monthly infusions could take several hours and were associated with a high incidence of side effects.

In 2006 the FDA approved the first subcutaneous immunoglobulin (SCIg) therapy for PID. Because SCIg can be self-administered, patients can schedule infusions to suit their own lifestyle. The dosage schedule  also allows patients to maintain more consistent immunoglobulin levels and for some, SCIg is also associated with fewer side-effects.

Last week, life got even better for these patients.  CSL Behring announced that the U.S. Food and Drug Administration (FDA) had granted marketing approval for Hizentra™, Immune Globulin Subcutaneous (Human), 20% Liquid. Hizentra is the first 20% concentration SCIg. This concentration enable patients to administer up to 20g of IgG in a single infusion, making it the first once weekly SCIg. It’s also the first SCIg to be stabilized with L-proline, allowing the product to be stored at room temperature.

“With its high concentration, Hizentra is a welcome new SCIg treatment option for patients managing primary immunodeficiencies,” said John Sleasman, M.D., Professor and Chief of the Division of Allergy, Immunology and Rheumatology at the University of South Florida College of Medicine, Department of Pediatrics. “Hizentra’s ready-to-use attribute will allow patients to infuse the product where and when it suits them, and physicians now have another product to select to best meet the individual needs of their patients.”

SRxA and Word on Health congratulate CSL Behring on developing a product that will truly improve the lives of patients with PID.