section name header

Information

Editors

JohannesSavolainen

Allergen Immunotherapy

Essentials

  • Allergen immunotherapy (also known as desensitization or hypo-sensitization) can be carried out either by giving subcutaneous injections or by sublingual immunotherapy, depending on the product and according to the marketing authorisation, from 5 years of age onwards, if the patient has an IgE-mediated allergic disease that impairs his/her quality of life.
  • It is recommended to start allergen immunotherapy at an early stage of an IgE-mediated allergic disease.
  • The physician and the nurse should actively discuss with the patient about allergen immunotherapy, since a large share of patients receiving such therapy have taken the issue up themselves.
  • The most common allergens used in the therapy include birch and timothy grass. More rarely used allergens include cat, dog, wasp, bee and house dust mite.
  • For sublingual immunotherapy, timothy grass, house dust mite and birch are the first more widely available allergen tablets.
  • The effect of allergen immunotherapy is good in allergic rhinitis and in allergy to Hymenoptera venoms both in adults and in children.
  • Allergen immunotherapy is also used in allergic asthma as a part of anti-inflammatory treatment with good effect both in adults and in children.

General

  • Allergen immunotherapy is the causal treatment of IgE-mediated
    • allergic rhinitis and conjunctivitis
    • allergic asthma and
    • allergy to wasp and bee venoms (i.e. Hymenoptera).
  • During allergen immunotherapy the allergic inflammatory reaction diminishes.
  • In allergy to Hymenoptera venoms, allergen immunotherapy suppresses any life-threatening reactions in 80% of patients and alleviates the severity of reactions in the rest 20%.
  • The treatment is usually continued for 3 years, in Hymenoptera allergy for 5 years.
  • The treatment has an effect in 80-90% of the patients. The effect lasts several years after the treatment has been stopped; in children with grass allergy it has been shown to last for 12 years.
  • The treatment is started by a physician with expertise in the investigation and treatment of allergic diseases.
  • Sublingual immunotherapy may be started even in primary care, in student health care services or in occupational health care, provided that the physician has adequate expertise.

Preconditions

  • General preconditions to be met before starting allergen immunotherapy
    • The patient has confirmed IgE-mediated allergy (allergic rhinoconjuctivitis) that causes symptoms.
    • There are no contraindications to the treatment.
    • The patient wishes to have the treatment.
    • Trained personnel are available to give and follow up the treatment according to current clinical guidelines.
  • The treatment can already be started at an early stage of the disease.
    • The risk of children allergic to pollen of birch or timothy grass to develop asthma may diminish when allergen immunotherapy is started sufficiently early.
  • Good patient guidance includes all information about the duration, expected efficacy and cost of the treatment as well as about the restrictions and possible adverse effects caused by it. This improves compliance.

Indications

  • The efficacy of each product in allergy to pollen, animals and house dust mite is presented below in the chapter Allergen immunotherapy products here. In allergy to Hymenoptera venoms allergen immunotherapy is the only effective causative treatment. Asthma in itself is hardly ever treated solely with allergen immunotherapy.
  • Allergy to Hymenoptera venoms
  • Allergic rhinitis and conjuctivitis caused by
    • pollens
    • house dust mite
    • animals/pets when indirect contact causes symptoms or when it is not possible to avoid direct contact (work, guide dogs)
  • Asthma caused by
    • pollens
    • house dust mite
    • animals/pets
  • Occupational allergies
    • animals

Contraindications

  • Asthma with poor control (FEV1 below 80%, z score <-1.65)
  • Active immunological or malignant disease
  • Severe heart and respiratory illnesses
  • Continuous oral glucocorticoid medication (over 10 mg of prednisolone or corresponding other glucocorticoid per day)
  • Beta-blocker medication (also as eye drops because in a severe reaction the effect of adrenaline is reduced)
  • Age under 5 years
  • Pregnancy and breastfeeding
  • Contraindications to injectable and sublingual allergen immunotherapy, as well as to immunotherapy for hymenoptera allergy are listed below, see table T1.

Contraindications to allergen immunotherapy. Source: Finnish Current Care Guideline Siedätyshoito [Allergen immunotherapy], Duodecim, 2019 http://www.kaypahoito.fi/en/ccs00046.

Illness, medication or other aspect to be consideredSubcutaneous immunotherapySublingual immunotherapyHymenoptera immunotherapy
Asthma (with poor control)AA2) A
Malignant tumourAAR
Pregnancy (starting therapy)AAA
Pregnancy (maintenance therapy)RRR
Diseases of the respiratory and circulatory systemRRN
Beta blockers1) RRN
ACE inhibitorsNNR
Active immunological disease, such as
  • autoimmune disease
AAA
  • HIV
RRR
  • AIDS
AAA
  • immunosuppressive medication
RRR
  • immune deficiencies
RRR
Chronic inflammatory disease in the oral cavityNAN
A = absolute contraindication
R = relative contraindication
N = not a contraindication
1) the efficacy of adrenaline may be decreased in the treament of anaphylaxis
2) does not apply to house dust mite desensitization
Subcutaneous immunotherapy

Practical aspects

  • The treatment is administered around the year by giving subcutaneous injections of aluminium hydroxide-bound depot allergen extracts.
  • During the updosing phase, which lasts 7 or 15 weeks, the injection dose is increased every 1-2 weeks. After the updosing phase the treatment can be given in a health care centre in cooperation with the centre where it was first started in accordance with the local practices and agreements.
  • In the maintenance phase the injections are usually given every 6 (4-10) weeks.
  • The maintenance dose is individual (the largest dose the patient can tolerate), but no more than recommended by the manufacturer of the allergen extract (the side-effects increase, but the effect does not).
  • The next dosage is dictated by the possible reaction from the previous injection and the symptoms the patient has at that time.
  • It is recommended to complete the updosing phase before the start of the pollen season.
  • The treatment duration is 3 years for inhaled allergens and 5 years for hymenoptera venoms.

Precautions

  • A qualified nurse should give the injections and a physician should always be present at the centre.
  • The patient is interviewed about possible reactions after the previous visit before giving the injection.
  • The patient should be observed for at least 30 minutes after the injection.
  • Patients below 15 years of age must be accompanied.
  • Intensive physical exercise and alcohol must be avoided after the injection.

Treatment-related reactions

  • Various injection reactions are a natural part of the treatment: local redness and swelling.
  • The dosage of the extract is estimated every time on the basis of the swelling reaction (a lump which can be felt and measured with the finger, not a possible prick lump on the skin!).
  • Generalized reactions (urticaria, asthma, fatigue, generalized allergic reaction) might occur.
  • The patient is given medication for the reactions:

Sublingual immunotherapy

  • Sublingual immunotherapy is effective and safe for allergic rhinitis and asthma caused by grass pollen, house dust mite, or birch.
  • The indications for sublingual immunotherapy are the same as for subcutaneous immunotherapy, and the contraindications are listed in table T1.
  • The first dose is administered at the nurse's office with a physician present.
  • The patient should be observed for at least 30 minutes after taking the tablet.
  • The tablet is placed under the tongue with dry, clean fingers immediately after taking the tablet from its package, and it is allowed to dissolve in the mouth.
  • Swallowing should be avoided for 1 minute after taking the tablet and eating or drinking should be avoided for 5 minutes.
  • After surgery of the mouth or dental procedures, the treatment is paused for 7 days. In children, a 1-day pause is warranted after shedding of a primary tooth (milk tooth).
  • If a patient with asthma has a respiratory infection, the treatment is paused for 7 days.
  • If the treatment is paused for 30 days or more, the patient should be instructed to contact the unit that started the therapy so that it can be restarted.

Allergen immunotherapy products

  • According to the recommendation by the WAO (World Allergy Organization), the evidence on the efficacy and safety of the different therapies is indicated below per product. The products and their names may vary accross countries.
  • Timothy grass sublingual tabletGrazax®
    • The treatment is effective, safe and well-tolerated in allergic rhinitis, both in adults 1 2 3 and children 4 5.
    • The treament may reduce asthma symptoms and the need for asthma medication in adults 6 7, and it apparently reduces the development of asthma symptoms and use of asthma medication in children with allergic rhinitis 8.
    • For adults and children from 5 years of age
  • House dust mite sublingual tabletAcarizax®
    • The treatment is effective, safe and well-tolerated in allergic rhinitis in adults 9 10 11 12 13 and, apparently, also in children 14 15.
    • Sublingual immunotherapy for asthma associated with house dust mite allergy apparently reduces the development of asthma symptoms in adults and adolescents 16 11 18 7.
    • Sublingual immunotherapy may reduce the need for asthma medication in adults and adolescents 20.
    • For adults (allergic rhinitis and asthma) and children from 12 years of age (allergic rhinitis)
  • Birch pollen sublingual tabletItulazax®
    • The treament is well-tolerated and reduces nasal and eye symptoms in adults with birch allergy 21 22 23 24.
    • For adults
  • Timothy grass subcutaneous immunotherapyAlutard SQ timotei®
    • The treatment reduces symptoms and it is well-tolerated in allergic rhinitis in adult patients 25 26.
    • For adults and children from 5 years of age
  • Birch subcutaneous immunotherapy Alutard SQ birch®
    • The treatment reduces symptoms and it is well-tolerated in allergic rhinitis in adult patients 27 28 26.
    • For adults and children from 5 years of age
  • House dust mite subcutanous immunotherapyAlutard SQ house dust mite®
    • The treatment is apparently effective and well-tolerated in allergic rhinitis in adults 30 31 32.
    • The treament may reduce the need for asthma medication in adults 33, children and adolescents 34.
    • For adults and children from 5 years of age
  • Cat subcutaneous immunotherapyAlutard SQ cat®
    • Research evidence is scarce concerning the effectiveness of the treatment in allergic rhinitis and asthma.
    • For adults and children from 5 years of age.
  • Dog subcutanous immunotherapyAlutard SQ dog®
    • Research evidence is scarce concerning the effectiveness of the treatment in allergic rhinitis and asthma.
    • For adults and children from 5 years of age.

Organization of treatment

  • Find out about the availability and organization of locally available allergen immunotherapy.

Follow-up

  • The doctor who first started the treatment should evaluate the efficacy annually.
  • This evaluation is based on the allergic symptoms and the use of other medication.
  • So-called VAS evaluation (visual analogue scale) is a method for evaluating efficacy. The patient may give his estimate of the effect yearly by using the VAS. The evaluation is based on changes in symptoms and use of medication during the treatment.

    References

    • Radulovic S, Calderon MA, Wilson D et al. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2010;(12):CD002893. [PubMed]
    • Dahl R, Kapp A, Colombo G et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;118(2):434-40. [PubMed]
    • Calderón M, Essendrop M. Specific immunotherapy with high dose SO standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol 2006;16(6):338-44. [PubMed]
    • Bufe A, Eberle P, Franke-Beckmann E et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 2009;123(1):167-173.e7. [PubMed]
    • Blaiss M, Maloney J, Nolte H et al. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol 2011;127(1):64-71, 71.e1-4. [PubMed]
    • Dahl R, Stender A, Rak S. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy 2006;61(2):185-90. [PubMed]
    • Durham SR, Emminger W, Kapp A et al. SQ-standardized sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 2012;129(3):717-725.e5. [PubMed]
    • Valovirta E, Petersen TH, Piotrowska T et al. Results from the 5-year SQ grass sublingual immunotherapy tablet asthma prevention (GAP) trial in children with grass pollen allergy. J Allergy Clin Immunol 2018;141(2):529-538.e13. [PubMed]
    • Demoly P, Emminger W, Rehm D et al. Effective treatment of house dust mite-induced allergic rhinitis with 2 doses of the SQ HDM SLIT-tablet: Results from a randomized, double-blind, placebo-controlled phase III trial. J Allergy Clin Immunol 2016;137(2):444-451.e8. [PubMed]
    • Nolte H, Bernstein DI, Nelson HS et al. Efficacy of house dust mite sublingual immunotherapy tablet in North American adolescents and adults in a randomized, placebo-controlled trial. J Allergy Clin Immunol 2016;138(6):1631-1638. [PubMed]
    • Virchow JC, Backer V, Kuna P et al. Efficacy of a House Dust Mite Sublingual Allergen Immunotherapy Tablet in Adults With Allergic Asthma: A Randomized Clinical Trial. JAMA 2016;315(16):1715-25. [PubMed]
    • Zieglmayer P, Nolte H, Nelson HS et al. Long-term effects of a house dust mite sublingual immunotherapy tablet in an environmental exposure chamber trial. Ann Allergy Asthma Immunol 2016;117(6):690-696.e1. [PubMed]
    • Bernstein DI, Kleine-Tebbe J, Nelson HS et al. SQ house dust mite sublingual immunotherapy tablet subgroup efficacy and local application site reaction duration. Ann Allergy Asthma Immunol 2018;121(1):105-110. [PubMed]
    • Maloney J, Prenner BM, Bernstein DI et al. Safety of house dust mite sublingual immunotherapy standardized quality tablet in children allergic to house dust mites. Ann Allergy Asthma Immunol 2016;116(1):59-65. [PubMed]
    • Masuyama K, Okamoto Y, Okamiya K et al. Efficacy and safety of SQ house dust mite sublingual immunotherapy-tablet in Japanese children. Allergy 2018;73(12):2352-2363. [PubMed]
    • Nolte H, Maloney J, Nelson HS ym. Effect of 12 SQ house dust mite sublingual immunotherapy tablet on asthma symptoms using an environmental exposure chamber. Ann Allergy Asthma Immunol 2015;115(5 Suppl 1):A112
    • de Blay F, Kuna P, Prieto L et al. SQ HDM SLIT-tablet (ALK) in treatment of asthma--post hoc results from a randomised trial. Respir Med 2014;108(10):1430-7. [PubMed]
    • Mosbech H, Deckelmann R, de Blay F et al. Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol 2014;134(3):568-575.e7. [PubMed]
    • Birk AO, Andersen JS, Villesen HH et al. Tolerability of the SQ Tree SLIT Tablet in Adults. Clin Ther 2017;39(9):1858-1867. [PubMed]
    • Couroux P, Ipsen H, Stage BS et al. A birch sublingual allergy immunotherapy tablet reduces rhinoconjunctivitis symptoms when exposed to birch and oak and induces IgG4 to allergens from all trees in the birch homologous group. Allergy 2019;74(2):361-369. [PubMed]
    • Mäkelä MJ, Gyllfors P, Valovirta E et al. Immunotherapy With the SQ Tree SLIT-tablet in Adults and Adolescents With Allergic Rhinoconjunctivitis. Clin Ther 2018;40(4):574-586.e4. [PubMed]
    • Biedermann T, Kuna P, Panzner P et al. The SQ tree SLIT-tablet is highly effective and well tolerated: Results from a randomized, double-blind, placebo-controlled phase III trial. J Allergy Clin Immunol 2019;143(3):1058-1066.e6. [PubMed]
    • Frew AJ, Powell RJ, Corrigan CJ et al. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117(2):319-25. [PubMed]
    • Calderon MA, Alves B, Jacobson M et al. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007;(1):CD001936. [PubMed]
    • Arvidsson MB, L�whagen O, Rak S. Effect of 2-year placebo-controlled immunotherapy on airway symptoms and medication in patients with birch pollen allergy. J Allergy Clin Immunol 2002;109(5):777-83. [PubMed]
    • Bødtger U, Poulsen LK, Jacobi HH et al. The safety and efficacy of subcutaneous birch pollen immunotherapy - a one-year, randomised, double-blind, placebo-controlled study. Allergy 2002;57(4):297-305. [PubMed]
    • Wang H, Lin X, Hao C et al. A double-blind, placebo-controlled study of house dust mite immunotherapy in Chinese asthmatic patients. Allergy 2006;61(2):191-7. [PubMed]
    • Dong X, Huang N, Li W et al. Systemic Reactions to Dust Mite Subcutaneous Immunotherapy: A 3-Year Follow-up Study. Allergy Asthma Immunol Res 2016;8(5):421-7. [PubMed]
    • Varney VA, Tabbah K, Mavroleon G et al. Usefulness of specific immunotherapy in patients with severe perennial allergic rhinitis induced by house dust mite: a double-blind, randomized, placebo-controlled trial. Clin Exp Allergy 2003;33(8):1076-82. [PubMed]
    • Blumberga G, Groes L, Haugaard L et al. Steroid-sparing effect of subcutaneous SQ-standardised specific immunotherapy in moderate and severe house dust mite allergic asthmatics. Allergy 2006;61(7):843-8. [PubMed]
    • Zielen S, Kardos P, Madonini E. Steroid-sparing effects with allergen-specific immunotherapy in children with asthma: a randomized controlled trial. J Allergy Clin Immunol 2010;126(5):942-9. [PubMed]