Subcutaneous Allergen Immunotherapy for Allergic Disease

Examining Efficacy, Safety and Cost-Effectiveness of Current and Novel Formulations

Linda Cox; Moisés Calderón; Oliver Pfaar

Disclosures

Immunotherapy. 2012;4(6):601-616. 

In This Article

Preventive Effect of SCIT on Asthma Development & New Allergen Sensitizations

SIT's unique disease-modifying effect may translate into reduced direct and indirect costs associated with AR and asthma. These savings may be a result of reduced current and long-term medication requirements and healthcare utilization as well as reduced progression of the allergic disease. This progression is often called the 'atopic march', which refers to the progression of AR to asthma and/or the development of new allergen sensitizations. AR is an identified risk factor for the development of asthma, with up to 40% of individuals with AR developing asthma later in life.[64–67]

The preventive benefit of SIT on asthma development was suggested as early as 1968 in a 14 year study that investigated the dose–response relationship of SCIT in asthmatic children randomized to receive either one of three doses of an allergen mixture or placebo.[68] At the age of 16 years, a dose-dependent difference in terms of being 'free of asthma' was demonstrated with the lowest incidence being in the group receiving the highest dose. There was essentially no difference between the lowest-dose and placebo groups.

One prospective, randomized, controlled, open-label study of 147 children, aged 16–25 years, evaluated the effect of a 3 year course of grass and/or birch pollen SCIT on the development of asthma compared with pharmacotherapy alone (referred to as the Preventive Allergy Treatment or PAT study).[69–71] SCIT was associated with a significantly lower incidence of asthma compared with pharmacotherapy alone at the end of treatment and at 5 and 7 years after discontinuation (OR: 2.5; 95% CI: 1.1–5.9 at 7 years).[69] The authors concluded that SCIT administered for 3 years results in a long-term preventive effect on the development of asthma.

The asthma-preventive effect of SCIT has also been demonstrated in the adult AR population. A 3 year, double-blind, RCT of 30 nonasthmatic AR adults assigned to receive Parietaria SCIT or placebo suggested that SCIT may prevent progression from AR to asthma.[72] At the end of the study, a time-dependent progression of asthmatic symptoms and asthma medication scores was apparent with nine of the 29 participants who completed the 3 year study developing asthma symptoms; of these, seven (47%) belonged to the placebo group whereas only two (14%) belonged to the SCIT-treated group (p = 0.056). In a subsequent 10 year retrospective study of 1104 nonasthmatic adults designed to investigate the natural history of AR and the potential effect of SCIT in reducing the incidence of asthma, the same authors found that the lowest risk factor for development of asthma was treatment with SCIT (OR: 0.53; 95% CI: 0.32–0.86).[73] AR at baseline was the highest risk factor associated with an asthma diagnosis at the end of follow-up (OR: 7.8; 95% CI: 3.1–20.00).[73]

A similar preventive effect was seen in a 3 year open-label study of 113 children, aged 5–14 years, with grass pollen rhinitis, who were randomized to receive coseasonal SIT for 3 years or standard symptomatic therapy.[74] There was a significantly higher incidence of new-onset asthma in the control group compared with the group who received SLIT. After 3 years, the frequency of asthma was 3.8-times greater for control subjects than for those receiving SIT (95% CI: 1.5–10.0).

In addition to preventing progression to asthma, several randomized, controlled and open-label studies have demonstrated that SCIT[56,75–77] may reduce the development of new allergen sensitizations. Three studies demonstrated a significantly lower incidence of new allergen sensitizations in monosensitized patients who received SCIT compared with matched controls who did not receive SCIT. New allergies developed in 23, 24 and 54% of those who received SCIT compared with 68, 67 and 100% of those who did not, respectively.[75–77] Similar results were found in a 3 year open-label study of 511 patients with AR ± asthma randomized to either SLIT or pharmacological treatment.[78] New allergen sensitizations developed in 38% of the control patients and in 5.9% of the SIT patients (p = 0.01).

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