Allergies > Doctors: Immunotherapy
Allergen immunotherapy is effective in the treatment of allergic rhinitis and benefits may persist for several years after treatment has stopped.
It can modify the progression of allergic disease and may prevent the development of new allergies.
It is administered subcutaneously, but local routes of administration are in development.
Mode of Action
During immunotherapy, allergenic extracts are repeatedly administered to a patient in order to reduce the symptoms that are triggered by subsequent allergen exposure. The extract is given in gradually increasing doses (until a maximum maintenance dose is reached), leading to desensitisation. Both early-phase and late-phase responses to allergen challenge may also be inhibited.
The mechanisms by which immunotherapy improves allergic rhinitis have not been completely elucidated, and many complex immune changes appear to be involved:
- Specific IgE antibody levels increase during the pollen season in people with seasonal allergic rhinitis, and return to baseline when the season ends. Allergen immunotherapy blunts this seasonal rise
- IgG antibodies increase following immunotherapy; it has been suggested that these may compete with IgE and block it binding to the antigen
- The inflammatory infiltrate of late phase responses may be inhibited, eg grass pollen immunotherapy inhibits the infiltration of CD4+ cells and eosinophils to the nasal mucosa
- Cytokines released by TH2 cells are thought to be involved in the inflammatory process in allergic rhinitis, and an excess of TH2 cells contributes to an allergic reaction. Immunotherapy may alter cytokine production by modifying the TH2 cell response
Efficacy of Immunotherapy
There have been over 40 placebo-controlled, double-blind studies on the use of subcutaneous immunotherapy (SIT) in rhinitis (primarily using pollen allergens, but also dust mite and mould allergens). The majority of these studies demonstrated efficacy of SIT compared with controls. A meta-analysis also concluded that specific immunotherapy is effective in the treatment of allergic rhinitis.
The benefits of SIT may persist for several years after discontinuation of treatment.
- Grass pollen immunotherapy taken for 3–4 years produced beneficial effects for at least a further 3 years
- In 40 asthmatic patients given dust mite immunotherapy for 12–96 months, 45% did not have further asthmatic or rhinitis symptoms for up to 3 years; the duration of treatment was related to the duration of the beneficial effects post-treatment
Immunotherapy may prevent the development of new sensitivities, particularly in children, as allergic sensitisation begins early in life (symptoms usually present within 10 years).
- In a study of asthmatic children under 6 years old and allergic to dust mites, those given SIT with standardised allergen extracts had a reduction in the development of multiple allergic sensitivities compared with controls
Recent studies have suggested that immunotherapy may prevent the development of asthma in children with allergic rhinitis.
- Preliminary results of the Preventive Allergy Treatment Study found that, in children with allergic rhinoconjunctivitis (allergic to birch and/or timothy pollen), immunotherapy for 2 years reduced the risk of onset of asthma compared with regular treatment.
Safety of Immunotherapy
The primary risk of allergen immunotherapy is a local or systemic anaphylactic reaction. From surveys and retrospective studies, the risk of a systemic reaction has been calculated as 0.1–1% per injection, and about 5% per patient per year. Systemic reactions range from mild to fatal. Surveys in the US suggest the likelihood of a fatal reaction is 1 per 2 million doses.
Injections must always be administered by, or under the close supervision of, a trained doctor who can recognise the early symptoms of anaphylaxis and administer emergency treatment.
Asthma appears to be a significant risk factor for systemic reactions. This is considered a contraindication in UK guidelines, but not in other national or international guidelines.
Selection of Patients
Immunotherapy may be indicated for patients with a limited spectrum of allergies:
- in whom other medications insufficiently control symptoms
- who do not wish to be on pharmacotherapy
- in whom pharmacotherapy produces side effects
- who do not want long-term pharmacological treatment
The use of allergen immunotherapy requires specialist assessment, particularly in children; it is rarely given to children under 5 years old.
Patients must have evidence of specific IgE antibodies to clinically relevant allergens and have symptoms that warrant the time and risk of allergen immunotherapy.
Patients must be made aware of the benefits and risks of all available therapeutic options.
Treatment of Programs
A subcutaneous immunotherapy (SIT) course involves a build up phase (escalating doses of allergen are given in weekly injections) and a maintenance phase (maximum allergen dose is administered every 1–2 months). Maintenance doses are usually reached within a few months. Build up phases can be shortened with accelerated programmes (involving twice weekly injections), but these increase the risk of systemic reactions.
Clinical benefits are usually apparent within months, and treatment is usually advised for 3–5 years.
Developments in Immunotherapy
The use of purified allergens, T cell reactive peptides, humanised anti-IgE monoclonal antibodies, and plasmid DNA immunisation is currently being investigated.
- A monoclonal antibody against IL-5 was found to reduce the level of blood eosinophils in asthmatic patients.
- Tighe et al conjugated Amb a 1 (the major allergen in ragweed pollen) to immunostimulatory DNA sequences derived from bacterial DNA that are known to stimulate TH1 responses. The allergen-DNA conjugate induced strong TH1 responses in mice, even in mice that had been primed to produce TH2 responses to the allergen. It also caused less histamine release from basophils in blood samples from human volunteers with ragweed allergy than the unconjugated allergen
In addition, novel routes of administration are being investigated. Recent studies have shown that intranasal and sublingual immunotherapy may be a viable alternative to subcutaneous immunotherapy (SIT). Treatment programmes for these are similar to those of SIT. Oral and bronchial administration have not been sufficiently studied to determine whether they are effective.
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