MEDICATIONS: ORAL ALTERNATIVE TO ALLERGY SHOTS RAISES CONCERNS IN THE U.S.

Nov. 5, 2005 — Oral/sublingual immunotherapy (SLIT), which has gained wide acceptance in the treatment of allergic disease throughout Europe and South America, is not a proven alternative to standard subcutaneous immunotherapy (SCIT, or "allergy shots") said U.S. experts at the Annual Meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Anaheim.

Currently there is no product for SLIT approved by the Food and Drug Administration (FDA), but Phase I clinical studies have begun in the United States for sublingual-oral administration of dust mite allergenic extracts.

Preliminary findings were unveiled on an ongoing comprehensive evaluation of SLIT for the North American allergy community by a Joint Task Force of the ACAAI and the American Academy of Allergy, Asthma and Immunology (AAAAI).

"After reviewing 100 published papers in English, French and German, in the areas of dosing, efficacy, immunologic response and safety, the Task Force concluded there is not enough evidence to determine minimum and maximum doses for sublingual immunotherapy at this time," said Linda S. Cox, M.D., Nova University Osteopathic School of Medicine, Fort Lauderdale, Fla., co-chair of the ACAAI/AAAAI SLIT Joint Task Force.

"Non-injection routes for immunotherapy date back to the early 1900s. SLIT has been used with increasing frequency in Europe in the past 20 years, and in some parts it is the predominant route of administration. Its purported main advantages over traditional immunotherapy are patient convenience, since it can be administered at home, and it appears to be safer than conventional immunotherapy," Dr. Cox said.

According to Anthony J. Frew, M.D., of the University of Southampton in the United Kingdom, the sublingual route of administration overcomes limitations associated with the conventional route, which he said requires a longer course of treatment and has reactions.

"Increased safety is the biggest advantage, as demonstrated in 22 studies with the reporting of only minor local side effects, such as itching, swelling or oral mucosa," said Dr. Frew. "Greater patient acceptability greatly improves adherence to the prescribed therapy regimen. It also saves staff and office costs, but this is partially offset by higher costs of extracts."

Other experts discussed the preponderance of literature demonstrating the efficacy and safety of SCIT in treating allergic rhinitis, allergic asthma, insect venom allergy. Allergy shots have been used since 1911. This time-tested therapy decreases a patient's sensitivity by introducing increasingly larger doses of the substances to which the patient is allergic. The treatment is a method for increasing the allergic patient's natural resistance to the things that are triggering the allergic reactions.

The immunization procedure begins with injections of small amounts of purified "extracts" of the substances that are causing allergic reactions. They are approved for this use by the FDA, and over the years they have been improved considerably.

"With conventional subcutaneous immunotherapy we have established dosing, duration, and have demonstrated its mechanism of action," said Harold S. Nelson, M.D., National Jewish Medical and Research Center in Denver.

"Long-term effects of SCIT have been shown for allergic rhinitis and asthma after therapy has been discontinued. Research also has demonstrated that SCIT prevents new sensitization and the progression from rhinitis to asthma," Dr. Nelson said.

Dr. Nelson summarized the results of two double-blind placebo-controlled studies conducted in cat allergic subjects, one employing SLIT and the other SCIT. The number of patients and the duration of treatment were similar, and both used exposure to cats before and after treatment to measure the response to immunotherapy. With SCIT symptoms improved only 4 percent with placebo but 72 percent with active treatment, a highly significant difference. With SLIT the placebo group improved 47 percent and the active group only 58 percent, a non-significant difference. Comparison of these two studies highlights the greater effectiveness of SCIT over SLIT, he noted.

Clinical studies have also demonstrated that SCIT improves seasonal allergic asthma, whereas there have been inconclusive findings on the effect of SLIT on asthma.

"Conventional immunotherapy has been shown to be effective in significantly improving lung function while reducing asthma symptoms and the need for medication," said Ira Finegold, RA Cook Institute of Allergy, St. Luke's-Roosevelt Hospital, New York.

Experts analyzed 75 trials involving 3,188 patients with asthma and found there was a significant reduction in asthma symptoms and medication. There also was improvement in bronchial hyper-reactivity following allergen immunotherapy. Another meta-analysis of 24 studies finding similar results showed immunotherapy was effective for all age groups and demonstrated that pulmonary function improved as well.

According to Dr. Finegold, the introduction of Omalizumab, a monoclonal IgE molecule with anti-IgE properties, has helped define asthma as an IgE-mediated disease. Anti-IgE (trade name Xolair) was approved by the Food and Drug Administration in June 2003 for use by patients who are age 12 and older, who have moderate-to-severe allergic asthma and have allergic asthma that has not responded well to other treatments such as SCIT immunotherapy, prescription antihistamines and inhaled corticosteroids.

"For patients with asthma, the use of Omalizumab has decreased hospital stays and asthma medication use while improving pulmonary function and the quality of life. Further, several studies have shown a benefit of combining conventional immunotherapy with administration of Omalizumab," Dr. Finegold said.

"Complete asthma control does not occur with pharmacotherapy. There is an urgent need to recognize that treating the allergic component with immunotherapy may be the solution. Oral/sublingual immunotherapy has generated much interest, and while it may eventually be approved as treatment in the United States, at the present it still remains unproven and not considered accepted therapy," he said.