Subcutaneous Allergen Immunotherapy for Allergic Disease

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

Linda Cox; Moisés Calderón; Oliver Pfaar


Immunotherapy. 2012;4(6):601-616. 

In This Article

Abstract and Introduction


Subcutaneous immunotherapy (SCIT) is a unique therapy for allergic disease because it provides symptomatic relief while modifying the allergic disease by targeting the underlying immunological mechanism. Its efficacy and safety have been established in the treatment of asthma, allergic rhinitis/rhinoconjunctivitis and stinging insect hypersensitivity in numerous controlled clinical trials. This review evaluates a spectrum of clinical factors, ranging from efficacy to cost–effectiveness, which should be considered in evaluating SCIT. The evidence for SCIT safety and efficacy for these conditions is reviewed in an evaluation of the systematic reviews and meta-analyses. The evidence for the persistent and preventive effects of SCIT is also examined. An overview of the SCIT outcomes measures utilized in clinical trials is presented. The cost–effectiveness of SCIT compared with conventional medication treatment, novel indications and formulations for SCIT are also explored in this review.


Subcutaneous immunotherapy (SCIT) has been employed in the treatment of allergic conditions for over a century, in a manner largely unchanged from the practice established by Noon and Freeman, the pioneers who first described successful treatment of grass pollen-induced hay fever with grass pollen inoculations.[1–3] Noon had been influenced by the work of William Dunbar, who believed a pollen 'toxin' was the cause of allergic rhinitis (AR).[4] Unfortunately, Dunbar's experiments with passive immunization utilizing serum from immunized rabbits and horses produced poor results and serious adverse events. Noon also believed a pollen 'toxin' was the cause of hay fever but, unlike Dunbar, was able to demonstrate effective treatment of hay fever patients with a protocol of increasing doses of grass pollen extract administered via subcutaneous injections. Using conjunctival allergen challenge, he established objective proof of SCIT efficacy by demonstrating that an immunotherapy-treated patient could tolerate an increase of up to 100-fold of allergen exposure before experiencing a conjunctival reaction.[3] He also showed that anaphylaxis may be induced by SCIT allergen 'overdose'. These early studies suggested that SCIT's clinical benefits may persist for at least 1 year after treatment cessation.[2] Subsequent clinical trials confirmed SCIT's persistent clinical benefits as well its possible preventive effect in terms of progression of the allergic disease from rhinitis to asthma or the development of new allergen sensitivities. In the ensuing century, multiple randomized controlled trials (RCTs) have demonstrated that SCIT is clearly effective and safe in the treatment of allergic asthma, rhinitis and stinging insect hypersensitivity and may be beneficial in other clinical conditions such as atopic dermatitis.

Although it has been over 100 years since SCIT's efficacy was first established, the mechanisms responsible for its efficacy are still being elucidated (Box 1). Despite this, multiple studies have demonstrated that both the efficacy and safety of SCIT are largely dependent on dose regardless of the specific allergen used. This paper will review the evidence for SCIT safety and efficacy beginning with an evaluation of the systematic reviews and meta-analyses for the approved indications discussed above. This evaluation will include a review of how SCIT outcomes are assessed and reported and novel formulations and indications for SCIT. The evidence for persistent and preventive effect of SCIT, as well as the cost–effectiveness of SCIT compared with conventional medication treatment, will also be examined.


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