Efficacy, dosage concerns unresolved on sublingual immunotherapy

Nov 7 2008

Although sublingual immunotherapy (SLIT) is used in Europe and other countries, experts at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI) in Seattle say questions remain unanswered regarding its effectiveness, appropriate use, dosage, and safety of administration.

“Sublingual immunotherapy has gained wide acceptance in the treatment of allergic disease throughout Europe and South America, but the research studies in the United States have yet to show results that will convince the FDA to approve a product,” said Ira Finegold, M.D., clinical professor of medicine at Columbia University and chairman of the R.A. Cook Institute of Allergy, St. Luke's-Roosevelt Hospital, New York.

“The main advantage of SLIT over traditional immunotherapy is patient convenience, since it is not an injection but oral drops or tablets that can be administered at home, and it appears to be safer than conventional immunotherapy,” he said.

Time-tested for a century, subcutaneous immunotherapy (SCIT), or allergy shots, has evolved into newer methods of administration. 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 Food and Drug Administration (FDA).

In SLIT – a therapy considered investigational/experimental in the United States – the absorption of the allergens into the body is through the membranes of the mouth. Although serious adverse events are rare, efficacy is somewhat less than with SCIT. Other comparisons between SLIT and conventional immunotherapy discussed at the meeting include dosing, duration of effectiveness after discontinuation and treatment for multiple sensitivities.

“We do not know the optimal dose for U.S. licensed allergen extracts for SLIT,” said Linda Cox, M.D., assistant clinical professor of medicine at Nova Southeastern University Osteopathic College of Medicine, Fort Lauderdale. “There is no consistent relationship between allergen dose and clinical efficacy. Each formulation including U.S. licensed extracts will need to demonstrate its effective dosing regimen.”

In contrast, the effective dosing range for conventional immunotherapy has been established for major allergens, and long-term effects of subcutaneous immunotherapy have been shown for allergic rhinitis and asthma after therapy has been discontinued.

The majority of allergic U.S. patients are sensitive to more than one allergen, but with the exception of one study, there have been no SLIT studies that have demonstrated efficacy with more than one non-cross reacting allergen Dr. Cox said. In one large population skin test survey (NHANES III) the median number of positive skin test was three.

“Since SLIT treatment is administered at home with no direct medical supervision, the physician will need to provide specific instructions to patients on how to manage adverse reactions, unplanned treatment interruptions, situations in which the dose should be withheld, and dosing adjustments for any or all of these variables,” Dr. Cox said.

The conclusions of a comparison study of 193 subjects on the long-term efficacy of subcutaneous and sublingual immunotherapies on perennial rhinitis suggest SLIT is a simpler and safer method of immunotherapy, said Harold S. Nelson, professor of medicine at both the University of Colorado and National Jewish Health in Denver. It is suitable for people not accepting SCIT or for seasonal allergic rhinitis. However, SCIT was better than SLIT for treatment of perennial allergic rhinitis due to house dust mites.

“Reported studies with high-dose SLIT show greater efficacy with each year of treatment up to three years. In one study with post-treatment follow-up, efficacy began to wane the third year after treatment,” Dr. Nelson said.

Evidence suggests SLIT may be beneficial for adults with mild allergic rhinitis caused by grass or tree allergy according to Paul A. Greenberger, M.D., professor of medicine, division of Allergy-Immunology at Northwestern University, Feinberg School of Medicine in Chicago. However, it may be unrealistic for trees and grasses with overlapping seasons, and some patients may still require medications.

“Although 35 percent of studies show at least a 30 percent reduction in some symptoms of rhinitis and use of medications with SLIT, some 40 percent of studies result in no reduction in symptoms and the need for medications,” Dr. Greenberger said.

Studies of SLIT-treated ragweed sufferers showed a 35 percent reduction in sneezing score, but no significant benefit for total rhinitis scores and no change in total medications or conjunctivitis scores.

“Can we recommend such a treatment when it isn't impressive as compared with SCIT? For poly-sensitized patients, we can't vouch for safety, patient satisfaction, or lack of benefits a patient would have getting care here in the office. The indications may increase if there are FDA approved products, CPT codes and appropriate reimbursement and satisfied patients,” he said.

SLIT has been shown to reduce some new sensitivities, which is a feature of conventional immunotherapy, Dr. Greenberger noted.

Studies have shown conventional immunotherapy may prevent the progression of allergic disease and reduce the risk of developing asthma; reduce the need for medication; reduce utilization and costs of health care services; and provide long term remission after discontinuation of treatment. Clinical studies have demonstrated that subcutaneous immunotherapy also improves seasonal allergic asthma, whereas there have been inconclusive findings on the effect of SLIT on asthma.

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