Immunological Comparison of AIT and SCIT Immunotherapy Against Grass Pollen
Condition: Allergic Rhinitis Due to Grass Pollens
MeSH terms: Rhinitis; Rhinitis, Allergic
Study type: Interventional

Summary: 
      Treatment of pollen allergies can be roughly divided into symptomatic treatment (e.g.
      antihistamines, steroids) and potentially curative immunotherapy. Immunotherapy can be
      delivered using subcutaneous or oral (mucosal) routes, with similar clinical outcome. The
      study seeks to compare immunological changes during subcutaneous (SCIT) and sublingual tablet
      (AIT) immunotherapy of grass pollen allergy (hayfever).
    

Detailed description: 
      Worldwide, more than 400 million people have allergic rhinitis, and sick-leave due to this
      condition costs societies billions of dollars annually1. Allergic rhinitis is most commonly
      treated with oral antihistamines and intranasal corticosteroids2. For moderate-severe
      rhinitis with poor control on topical treatment, immunotherapy should be considered3.
      Allergen immunotherapy is the only disease-modifying treatment available for IgE mediated
      allergy.

      Immunotherapy is most commonly administered with subcutaneous injections of SQ-standardized
      allergen extracts (SCIT) and to a lesser extent, as sublingual drops (SLIT). However, other
      options now exist with the newly developed sublingual allergen immunotherapy tablets (AIT).
      The clinical effect of AIT4 and SCIT5 against grass pollen allergy has been demonstrated in
      large double-blind-placebo-controlled registration trials. These studies report significant
      reductions of symptom scores (AIT 30%, SCIT 32%) and seasonal rescue medication scores (AIT
      38%, SCIT 41%) when compared with placebo4,5, persisting several years after withdrawal4,6.
      Immunotherapy may prevent new sensitizations and progression of rhinitis to asthma7-11.
      Allergen immunotherapy is generally well tolerated with few side effects, although a
      potential risk of anaphylactic reactions exists 12. A review of recent parallel meta-analyses
      on immunotherapy for grass pollen rhinitis suggests that the safety profile of AIT is
      superior to that of SCIT13.

      The recommended length of immunotherapy with both SCIT and AIT is 3-5 years2, although the
      route of administration and the doses of allergen differ substantially. SCIT involves an
      up-dosing phase lasting 12-15 weeks with one or more weekly injections of increasing doses of
      allergen followed by a maintenance dose every 6-10 weeks. AIT starts with the daily
      maintenance dose, resulting in high cumulative doses. It is largely unknown whether the
      immunological mechanisms involved in the clinical effect are the same.

      The changes in immunology have been extensively investigated for SCIT, and the most
      pronounced patterns are: 1) the induction of blocking antibodies, 2) a shift in Th1/Th2
      balance towards Th1, and 3) induction of regulatory T cells. Similar mechanisms seem to be in
      play for AIT 14-16. Increases in allergen-specific non-IgE antibodies have been demonstrated
      in large trials of both SCIT and AIT treatment17,18, and studies have demonstrated that serum
      antibodies can reduce in vitro reactions mimicking allergic responses, such as IgE binding to
      allergen, IgE facilitated antigen presentation and basophil activation19-22, suggesting that
      both humoral and cellular effects play a role23.

      The aim of the present study was to compare the effect of AIT and SCIT on antibody titers
      (IgE and IgG4), on allergen-IgE interaction in competition assays (IgE-blocking factor and
      FAP inhibition) and on effector cell activation (BAT). Nasal challenges were included to
      assess the changes in nasal response to grass pollen allergen.
    

Intervention name(s): ALK Grazax 75,000 SQ-T "Phleum pratense"; ALK AluTard 225 "Phleum pratense"
Intervention type(s): Drug; Drug
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Basic Science