Pharmacoeconomics of subcutaneous allergen immunotherapy.

The current burden of allergic diseases, estimated by both direct and indirect costs, is very relevant. In fact the cost estimation for rhinitis amount globally to 4-10 billion dollars/year in the U.S. and to an average annual cost of 1089 euros per child/adolescent and 1543 euros per adult in Europe. The estimated annual costs in Northern America for asthma amounted to 14 billion dollars. Consequently, preventive strategies aimed at reducing the clinical severity of allergy are potentially able to reduce its costs. Among them, specific immunotherapy (SIT) joins to the preventive capacity the carryover effect once treatment is discontinued. A number of studies, mainly conducted in the US and Germany demonstrated a favourable cost-benefit balance. In the nineties, most surveys on patients with allergic rhinitis and asthma reported significant reductions of the direct and indirect costs in subjects treated with SIT compared to those treated with symptomatic drugs. This is fully confirmed in recent studies conducted in European countries: in Denmark the direct cost per patient/year of the standard care was more than halved following SIT; in Italy a study on Parietaria allergic patients demonstrated a significant difference in favor of SIT plus drug treatment for three years versus drug treatment alone, with a cost reduction starting from the 2nd year and increasing to 48% at the 3rd year, with a highly statistical significance which was maintained up to the 6th year, i.e. 3 years after stopping immunotherapy, corresponding to a net saving for each patient at the final evaluation of 623 euros per year; in France a cost/efficacy analysis comparing SIT and current symptomatic treatment in adults and children with dust mite and pollen allergy showed remarkable savings with SIT for both allergies in adults and children.

Economic evaluation of sublingual immunotherapy: an analysis of literature.

Allergic rhinitis and asthma constitute a global health problem because of their very high prevalence and the consequent burden of disease, concerning medical and economical issues. Among the treatments of allergy, specific immunotherapy has the capacity to favourably alter the natural history of the disease both during and after its performance and thus to reduce the direct and indirect costs of allergic rhinitis and asthma. A number of studies reported such cost reduction for traditional, subcutaneous immunotherapy and recent data demonstrate that also sublingual immunotherapy (SLIT) is associated to economic advantages and/or monetary savings, specifically in terms of reduction of disease economic burden. Only few formal economic assessments of SLIT have been carried out so far, this article will present and discuss the published studies addressed to this issue. The data obtained, although the number of studies is still limited, provide preliminary evidence supporting a SLIT effect on sparing costs for respiratory allergy.

Dose dependence of efficacy and safety of subcutaneous immunotherapy.

A number of experimental and clinical evidence has shown that exposure to high amounts of allergen molecules favours the development of tolerance. This is true also for subcutaneous immunotherapy (SCIT), for which a dose dependence of clinical efficacy was clearly demonstrated. The effective doses, measured as microg of major allergens, to be administered during maintenance treatment were established for the main allergens. Regarding pollens, the range of effectiveness corresponds to 25-41 and 13-20 microg of major allergens Phl p 5 and Phl p 6 for grasses, to 10-47 microg of Amb a 1 for ragweed, to 12 microg of Bet v 1 for birch, and to 6.2 microg of Par j 1 for Parietaria. With house dust mites, a maintenance dose of 5-11.5 microg of the major allergen from Dermatophagoides pteronyssinus Der p 1 is associated to clinically relevant effects, and with cat epithelium the clinical success is observed using a dose of 13-15 microg of Fel d 1. Nevertheless, there are adverse reactions facing SCIT, which are related to the amount of injected allergen. In fact, the safety decreases when the administered doses increase. This has led to "optimal doses" being defined which show a good balance between efficacy and safety (corresponding for example to a dose of 7 microg for Der p 1 and of 13 microg for Fel d 1). The dose dependency with respect to both efficacy and safety makes essential to accurately consider the risk/benefit ratio in each patient eligible for SCIT.

Dose dependence of efficacy but not of safety in sublingual immunotherapy.

Sublingual immunotherapy (SLIT) currently represents, as indicated by meta-analysis of its efficacy and safety, a valid option to the generally used traditional subcutaneous immunotherapy (SCIT) for treating respiratory allergy. Regarding efficacy, recent studies demonstrated that, similar to what has already been observed in SCIT as well as in experimental and clinical studies about the magnitudo of allergen exposure, the effectiveness on both clinical symptoms and immunologic changes depends on the amount of allergen administered during treatment. In addition, in vitro studies addressed with the role of dendritic cells, currently considered to be of pivotal importance in orienting toward tolerance the immune response to allergens, showed that the internalisation of allergen molecules, which is followed by tolerogenic presentation to T cells, depends on the amount of allergen. However, such dose dependence is not apparent concerning the safety. In fact, the comparison of studies respectively conducted with high and low allergen doses did not show differences in the rate of systemic reactions, which in any case never had the presentation of anaphylaxis, and instead a significant difference in the rate of local reactions, following the oral and gastrointestinal contact with the allergen extract, in favour of high dose studies.

Pollen-related allergy in Italy.

Pollen-related allergies are very common in Italy and pollinosis is the commonest allergic disease. The type of allergenic plants and the prevalence of hay fever varies among regions. In the Mediterranean area there are characteristic climatic conditions (mildness of winter, summer dryness) that facilitate the growth of a typical vegetation with its associated various types of allergenic pollen grains, some of them very different from those of central and northern Europe. Italy has a central position in the Mediterranean basin, but because of its geographic characteristics, there are different climatic aspects with different vegetation between northern, central, and southern areas. Gramineae are the most common allergenic plants in northern and central Italy, where more than 60% of patients with pollinosis are grass-pollen sensitive. Parietaria is the most important pollinating plant in southern Italy and Liguria. Olea europaea, the olive tree with cultivation widespread in the whole Mediterranean basin, is responsible for frequently severe pollinosis, particularly in some regions of the southern Italy.