CHICAGO-- Allergy shots have been used for almost a century to treat patients with allergic rhinitis or asthma. But does this form of immunotherapy really work--or is it, as some critics have claimed, no better than placebo? Several new meta-analyses suggest that immunotherapy--with specific standardized and potent extracts--improves allergy and asthma symptoms, reduces medication needs in some patients with allergen-triggered asthma and allergic rhinitis, and prevents the progression of allergic rhinitis. It may even reduce costs for some patients. However, careful patient selection is the key to maximizing the benefits from immunotherapy.

Although immunotherapy has been a hallmark of care among allergists for decades, considerable controversy remains regarding its clinical efficacy and economic consequences, especially in patients with asthma. Some clinicians question whether immunotherapy is really necessary, considering the array of new drugs that target allergy and asthma symptoms. To address these issues, a series of meta-analyses were undertaken to assess the effectiveness of specific immunotherapy (vaccination against specific allergens) in the treatment of allergic rhinitis, asthma, and insect venom hypersensitivity. Results were presented at the recent annual meeting of the American College of Allergy, Asthma, and Immunology (ACAAI).

Three of the meta-analyses were conducted by Robert Ross, PhD, Ira Finegold, MD, and Harold Nelson, MD. A similar meta-analysis was performed by Michael Abramson, MB, PhD, and colleagues from Australia.

FEWER SYMPTOMS, DECREASED MEDICATION USE

The meta-analysis by Ross et al of allergic rhinitis included 16 studies in which 416 subjects had received immunotherapy (either grass or ragweed extract) and 343 had been given placebo. Immunotherapy was clinically effective in all but one study, and that study had methodological flaws, according to the investigators. Ross et al also found that symptom-medication scores were significantly lower in the subjects who received immunotherapy than in the placebo group.

The second meta-analysis was based on 24 studies that compared the effectiveness of standard asthma treatment alone with a combination of standard asthma treatment and specific immunotherapy. Subjects included 962 patients with allergic asthma. Immunotherapy was found to be effective in 17 of these studies (71%), ineffective in four (17%), and equivocal in three (12%). However, most of the studies in which immunotherapy was ineffective were conducted at least 15 years ago and tested only house-dust immunotherapy, which may limit their relevance to current treatment approaches, the investigators noted.

Overall, Ross et al found that patients who received specific immunotherapy experienced a greater reduction in asthma symptoms than did those who received only standard treatment. Consequently, there was a significant reduction in the use of medications in those patients who received immunotherapy. Specific immunotherapy also appeared to improve pulmonary function and provide protection against bronchial challenge.

The third meta-analysis examined venom injection therapy for hymenopteran venom sensitivity. Thirty articles were identified, but only eight were placebo-controlled. Most studies used honeybee and yellow-jacket venom. All of the studies demonstrated that venom immunotherapy was effective in reducing the risk from repeat hymenopteran stings.

INTERNATIONAL PERSPECTIVES

Hans-Jørgen Malling, MD, and colleagues from the University of Copenhagen in Denmark analyzed the results of 59 double-blind, placebo-controlled trials of specific immunotherapy that included symptom-medication scores. They found that of the 43 studies that included patients with allergic rhinitis, six demonstrated high-grade efficacy, 14 found moderate-grade efficacy, and 13 suggested low-grade efficacy. However, the remaining 10 studies found no benefit. The mean clinical improvement in symptom-medication scores with treatment was 45%. The best results were obtained in patients with grass pollen allergies.

Of the 16 studies that evaluated asthma patients, four demonstrated high-grade efficacy, another four found moderate-grade efficacy, and three suggested low-grade efficacy. No benefit was detected in five studies.

The mean reduction in disease severity was 40%. Patients with allergies to grass pollen or cats were most likely to respond to specific immunotherapy.

PATIENT SELECTION: KEY TO SUCCESS

As these results suggest, successful outcome with specific immunotherapy requires careful patient selection. According to Dr. Malling, who is an associate professor at the University of Copenhagen, the patients most likely to respond include:

• Patients with symptoms primarily induced by allergens.
• Patients with sensitivity to a single or few allergens.
• Young patients without chronic irreversible changes in the airway.

Those with a chronic inflammatory process in the airways may not benefit from this form of treatment. In addition, the precise identification of the responsible allergens is necessary.

IMMUNOTHERAPY CUTS COSTS

According to the ACAAI, the direct and indirect costs of allergic rhinitis and asthma total several billion dollars annually; medications alone account for over a billion dollars each year. The meta-analyses have demonstrated that immunotherapy reduces the need for medications in patients with allergic rhinitis and asthma by 80% and 88%, respectively. What impact does this reduction have on the total cost of care?

Timothy J. Sullivan, III, MD, a professor of medicine at Emory University in Atlanta, examined this issue. He estimated that yearly drug costs for perennial allergic rhinitis and for moderately severe asthma are $1,200 and $1,000, respectively.

He then calculated that the cost for the first year of immunotherapy is approximately $800, and costs for subsequent years range from $170 to $290. Thus, he estimated that immunotherapy would reduce total costs over six years by $1,300 to $2,900 for a patient with perennial allergic rhinitis.

For a patient who has both perennial allergic rhinitis and asthma, cost reductions over the same six years could reach as high as $7,000. However, the costs would increase (by $730 over six years) for a patient who has seasonal allergic rhinitis, although the improvement in symptoms might justify the added expense, Dr. Sullivan said.

--Janis Kelly