Egging on Allergies?

Friends, family, colleagues and regular readers of SRxA’s Word on Health already know about my egg allergy.  What they may not know about is my egg aversion.  Just typing the “e” word makes me queasy.  Thinking about eggs makes me cringe and actually seeing them, especially hard boiled, fills me with revulsion.

So, with some trepidation, I bring you this breaking health story.

According to a study just published in the New England Journal of Medicine by giving children with egg allergies increasingly higher doses of the very food they are allergic to researchers found they could eliminate or ease reactions in most of them.

The study conducted at Johns Hopkins Children’s Center and four other U.S. institutions treated 40 egg allergic children with escalating doses of eggs – an approach known as oral immunotherapy.

In the 10 month study, 40 children, aged 5 -18, received escalating doses of egg-white powder while 15 received a cornstarch placebo.  35 of the 40 children treated with egg immunotherapy experienced improvement. Five dropped out of the study, four of them due to allergic reactions. Eleven of the 35 patients experienced complete long-term elimination of egg-related allergic reactions. The rest of the children were able to tolerate higher doses of egg with only mild or no symptoms.

“More than a quarter of the children in our study lost their egg allergies altogether, but we also saw dramatic improvements in those who didn’t, which in and of itself is an important therapeutic achievement,” says Robert Wood, M.D, director of allergy and immunology at Johns Hopkins Children’s Center. “These children went from having serious allergic reactions after a single bite of an egg-containing cookie to consuming eggs with minimal or no symptoms.”

This is important because it can protect against serious allergic reactions from accidental or incidental exposures and give patients and parents a peace of mind at restaurants, parties and other venues where food control is difficult or impossible.

But while this may be good news for the estimated 3% of U.S. with egg allergies, this blogger is not so sure she’d be a candidate.  The thought of having to eat escalating doses of the dreaded “e” word is more abhorrent to me than the thought of a future filled with quiche and ice cream!

On a more serious note, we’d also like to brings readers some sage advice from allergist David Amrol MD : “Although oral immunotherapy is our best chance for a food allergy cure, it is not ready for mainstream use until protocols are further refined. Patients who are not enrolled in clinical trials must continue to rely on allergen avoidance, patient education, and self-injectable epinephrine.”

Pharma Ads Under Fire

Although the back-to-school season has barely begun, both the pharmaceutical industry and the FDA have already received “could do better” report cards. According to researchers from Mount Sinai School of Medicine, only 18% of 192 pharmaceutical advertisements in biomedical journals were compliant with FDA guidelines.  And, over half failed to include serious risks including death. The study, was the first in almost 20 years to provide a systematic assessment of the adherence of US pharmaceutical ads to FDA guidance. Researchers looked at prescription pharmaceutical ads published in nine major peer-reviewed journals, including: the Annals of Internal Medicine,  Blood,  JAMA and the New England Journal of Medicine, during the month of November 2008.  They evaluated adherence to FDA standards and the presence of safety information.  Of the 192 advertisements for 82 unique products, only 15 fully adhered to all 20 FDA Prescription Drug Advertising Guidelines. Advertisements contained bias with regard to a wide variety of issues:

• 57.8% of the advertisements did not quantify serious risks
• 48.2% lacked verifiable references
• 28.9% failed to present adequate efficacy quantification

However, despite the high rates of FDA non-adherence, the mean number of biased features in each advertisement was low and most advertisements they reviewed satisfied the majority of FDA guidelines. Part of the problem it seems is that the FDA emphasizes avoiding frankly false information and balancing efficacy and safety information  but does little to encourage the presentation of useful and accurate information.  For example, an ad containing no specific efficacy claim, no quantification of drug safety and no verifiable references would adhere fully to FDA guidelines, despite presenting no practical information for clinicians.

Dr. Deborah Korenstein, lead author of the study and Associate Professor of Medicine at Mount Sinai School of Medicine is concerned by the lack of adherence. “While the majority of physicians deny that advertisements inform their prescribing marketing research has consistently shown that journal advertising is the most profitable form of drug marketing, with an estimated return on investment of $5 for every dollar spent.” She does however acknowledge that it may be unrealistic to expect  ads to inform rational prescribing by presenting complete drug safety and efficacy, since they primarily serve a marketing function and are not designed to train physicians to prescribe.  Her advice?  “Physicians should ensure that their prescribing is informed by the clinical literature and not by marketing materials.” She also notes that the findings have important policy implications. Although he FDA has already demonstrated a desire to improve the quality of pharma ads, by enlisting doctors to review advertisements through its “Bad Ad” program, Korenstein suggests that the current FDA guidelines are subjective, challenging to enforce and do not emphasize transparency and the inclusion of basic information relevant to prescribing. She suggests that the FDA should update and simplify its guidelines for physician ads. According to her, guidelines should be straightforward and objective. They should ensure that ads present clear risk quantification, absolute benefit information, description of the appropriate population to receive the drug, and verifiable references to published peer-reviewed  literature. In other words, the FDA may hold the key to improving the quality of pharmaceutical advertisements rather than the industry itself.

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.