Allergen immunotherapy: Where is it now?
2007; Elsevier BV; Volume: 119; Issue: 4 Linguagem: Inglês
10.1016/j.jaci.2007.01.036
ISSN1097-6825
Autores Tópico(s)Dermatology and Skin Diseases
ResumoThe scientific basis and the proof of clinical effectiveness of allergen immunotherapy administered by subcutaneous injection (SCIT) are well established. It is effective treatment for sensitivity to Hymenoptera venom and for allergic rhinitis and allergic asthma. SCIT administered in the proper setting reduces the development of new sensitivities and progression from rhinitis to asthma. Further, the beneficial effects persist long after completion of a course of treatment. Although many people enjoy the benefits of SCIT, extension of its use to the many others who might be candidates for this treatment is limited by its drawbacks of safety concerns and the inconvenience of repeated clinic visits over several years to receive the injections. There are many attempts underway to improve on the safety and convenience while still retaining the benefits of SCIT. These include approaches using current allergen extracts, especially by administering them sublingually. Alternatively, through recombinant technology, extracts are being modified to reduce their allergenicity without reducing their immunogenicity. They are being linked to immunostimulatory DNA sequences that will modify their in vivo processing resulting in an enhanced nonallergic response or they are being incorporated into fusion proteins with inhibitory properties for mast cells and basophils. The scientific basis and the proof of clinical effectiveness of allergen immunotherapy administered by subcutaneous injection (SCIT) are well established. It is effective treatment for sensitivity to Hymenoptera venom and for allergic rhinitis and allergic asthma. SCIT administered in the proper setting reduces the development of new sensitivities and progression from rhinitis to asthma. Further, the beneficial effects persist long after completion of a course of treatment. Although many people enjoy the benefits of SCIT, extension of its use to the many others who might be candidates for this treatment is limited by its drawbacks of safety concerns and the inconvenience of repeated clinic visits over several years to receive the injections. There are many attempts underway to improve on the safety and convenience while still retaining the benefits of SCIT. These include approaches using current allergen extracts, especially by administering them sublingually. Alternatively, through recombinant technology, extracts are being modified to reduce their allergenicity without reducing their immunogenicity. They are being linked to immunostimulatory DNA sequences that will modify their in vivo processing resulting in an enhanced nonallergic response or they are being incorporated into fusion proteins with inhibitory properties for mast cells and basophils. As the practice of allergen immunotherapy approaches its 100th anniversary, major changes appear likely in the way it is practiced. The scientific rationale for immunotherapy has never been stronger. However, extension of the use of allergen immunotherapy to the many appropriate patients is hampered by 2 continuing drawbacks: concerns for safety and, because of these real concerns, the inconvenience of the treatment schedules used. In response to these drawbacks, attention is being given to developing safer and more convenient ways to administer the currently available allergen extracts or to making modifications in the allergen extracts, rendering them inherently safer and more convenient. It will be important, however, not to sacrifice the effectiveness of the current method of administering immunotherapy while seeking greater safety and convenience. As a background, this article reviews where we are in 2007 with immunotherapy using subcutaneous injections of unmodified extracts in aqueous or glycerin solutions with or without adsorption to alum. We then consider the alternative approaches that have advanced to clinical application, particularly the administration of allergen extracts sublingually.Subcutaneous immunotherapyEstablished aspectsDiseases or conditions in which subcutaneous immunotherapy is effectiveCurrently subcutaneous immunotherapy (SCIT) is established as effective treatment for patients with IgE-mediated reactions to hymenoptera venom,1Ross R.N. Nelson H.S. Finegold I. Effectiveness of specific immunotherapy in the treatment of hymenoptera venom hypersensitivity: a meta-analysis.Clin Ther. 2000; 22: 351-358Abstract Full Text PDF PubMed Scopus (101) Google Scholar allergic rhinitis,2Ross R.N. Nelson H.S. Finegold I. Effectiveness of specific immunotherapy in the treatment of allergic rhinitis: an analysis of randomized prospective, single- or double-blind, placebo-controlled studies.Clin Ther. 2000; 22: 342-350Abstract Full Text PDF PubMed Scopus (119) Google Scholar and allergic bronchial asthma.3Abramson M.J. Puy R.M. Weiner J.M. Allergen immunotherapy for asthma.Cochrane Database Syst Rev. 2003; 4 (CD001186)PubMed Google ScholarEffective doses of allergen extractA problem in discussing doses for immunotherapy is the many ways allergen extract strength is expressed, some of which, such as weight by volume and protein nitrogen units, have no relation to allergenic potency—that is, the quantity of allergenic proteins per unit volume of extract. Even when relevant measures are used, such as the reaction on skin testing of subjects with allergy or in vitro inhibition assays, the units employed to express the results are often unique to a particular company or regulatory agency and are not interconvertible. Furthermore, measures of total allergenic potency are unable to detect differences in the relative amounts of the major allergens within the extract. For all the shortcomings in the use of major allergen content to express extract potency and dosing,4Grier T.J. Hazelhurst D.M. Duncan E.A. West T.K. Esch R.E. Major allergen measurements: sources of variability, validation, quality assurance, and utility for laboratories, manufacturers and clinics.Allergy Asthma Proc. 2002; 29: 125-131Google Scholar it remains the only international language currently available. Double-blind, placebo-controlled studies have been conducted with extracts of all of the allergens currently standardized in the United States, although only a few have been conducted with the US extracts. The effective dose may be expressed as the quantity of the major allergen delivered as a maintenance dose (Table I).5Creticos P.S. Adkinson N.F. Sobotka A. Proud D. Meier H.L. Naclerio R.M. et al.Nasal challenge with ragweed pollen in hay fever patients: effect of immunotherapy.J Clin Invest. 1985; 76: 2247-2253Crossref PubMed Scopus (181) Google Scholar, 6Furin M.J. Norman P.S. Creticos P.S. Proud D. Sobotka A. Lichtenstein L.M. Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity.J Allergy Clin Immunol. 1991; 88: 27-32Abstract Full Text PDF PubMed Scopus (164) Google Scholar, 7Creticos P.S. Marsh D.G. Proud D. Sobotka A. Adkinson N.F. Friedhoff L. Responses to ragweed-pollen nasal challenge before and after immunotherapy.J Allergy Clin Immunol. 1989; 84: 197-205Abstract Full Text PDF PubMed Scopus (96) Google Scholar, 8Frew A.J. Powell R.J. Corrigan C.J. Durham S.R. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 319-328Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar, 9Varney V.A. Edwards J. Tabbah K. Brewster H. Mavroleon G. Frew A.J. Clinical efficacy of specific immunotherapy to cat dander: a double-blind, placebo-controlled trial.Clin Exp Allergy. 1997; 27: 860-867Crossref PubMed Scopus (156) Google Scholar, 10Khinchi M.S. Poulsen L.K. Carat F. Andre C. Hansen A.B. Malling H.J. Clinical efficacy of sublingual and subcutaneous Birch pollen allergen specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study.Allergy. 2004; 59: 45-53Crossref PubMed Scopus (219) Google Scholar, 11Rak S. Heinrich C. Schevnius A. Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy.Allergy. 2005; 60: 643-649Crossref PubMed Scopus (10) Google Scholar, 13Ewan P.W. Alexander M.M. Snape C. Ind P.W. Agrell B. Dreborg S. Effective hyposensitization in allergic rhinitis using a potent partially purified extract of house dust mite.Clin Allergy. 1988; 18: 501-508Crossref PubMed Scopus (106) Google Scholar, 14Haugaard L. Dahl R. Jacobsen L. A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects.J Allergy Clin Immunol. 1993; 91: 709-722Abstract Full Text PDF PubMed Scopus (194) Google Scholar, 15Olsen O.T. Larsen K.R. Jacobsen L. Svendsen U.G. A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults.Allergy. 1997; 52: 853-859Crossref PubMed Scopus (97) Google Scholar, 16Alvarez-Cuesta E. Cuesta-Herranz J. Puyana-Ruiz J. Cuesta-Herranz C. Blanco-Quiros A. Monoclonal antibody-standardized cat immunotherapy: risk benefit effects from a double-blind study.J Allergy Clin Immunol. 1994; 93: 556-566Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 17Hedlin J.G. Lonnevig V. Heilbron H. Lilja G. Norrlind K. Pegelow K. Immunotherapy with cat- and dog-dander extracts, V: effects of 3 years of treatment.J Allergy Clin Immunol. 1991; 87: 955-964Abstract Full Text PDF PubMed Scopus (132) Google Scholar, 18Ewbank P.A. Murray J. Sanders K. Curran-Everett D. Dreskin S. Nelson H.S. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract.J Allergy Clin Immunol. 2003; 111: 155-161Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 19Nanda A. O'Connor M. Anand M. Dreskin S.C. Zhang L. Hines B. et al.Dose dependence and time course of the immunologic response to administration of standardized cal allergen extract.J Allergy Clin Immunol. 2004; 114: 1339-1344Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar, 20Lent A. Harbeck R. Strand M. Sills M. Schmidt K. Efaw B. et al.Immunological response to administration of standardized dog allergen extract at differing doses.J Allergy Clin Immunol. 2006; 118: 1249-1256Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar, 21Horst M. Hejjaoui A. Horst V. Michel F.-B. Bousquet J. Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract.J Allergy Clin Immunol. 1990; 85: 460-472Abstract Full Text PDF PubMed Scopus (213) Google Scholar Expressed in this way, the range of doses is seen to be relatively narrow (3-20 μg major allergen), with the exception of Alternaria, for which significant improvement was achieved with a dose containing only 1.6 μg of the major allergen Alt a 1.12Olaquibel J.M. Tabar A.I. Garcia B.E. Martin S. Rico P. Long-term immunotherapy with an optimal maintenance dose of a standardized Dermatophagoides pteronyssinus extract in asthmatic patients.J Investig Allergol Clin Immunol. 1999; 9: 110-116PubMed Google Scholar Information on dose responses is available for most of the extracts (Table I). In general, a dose 1/5 to 1/10 of the proven effective dose has been less effective or ineffective in eliciting the responses being assessed (Table I). Because, of the US standardized extracts, only cat and ragweed are standardized by major allergen, the content of major allergen varies quite widely for extracts of the same expressed potency. Nevertheless, information on the mean major allergen content of an extract is often available from the extract manufacturer (Table II). The markedly lower major allergen content of cat and house dust mite extracts is reflected in their lower Allergen or Bioequivalent Allergen Unit rating by the US system of expressing standardized extract potency. Because approximately the same amount of major allergen is required for effective immunotherapy with these weaker extracts (Table I), it follows that larger volumes of these extracts must be either administered as monotherapy or compounded into a treatment set (Table III). Studies of dosing with nonstandardized extracts are not performed because the results could not be applied to other manufacturers' extracts or even to other lots from the same manufacturer. However, on the basis of a limited number of analyses, it appears that most nonstandardized pollen extracts are of similar potency to the standardized ragweed and grasses and may be dosed accordingly.22Lavins B.J. Dolen W.K. Nelson H.S. Weber R.W. Use of standardized and conventional allergen extracts in prick skin testing.J Allergy Clin Immunol. 1992; 89: 658-666Abstract Full Text PDF PubMed Scopus (17) Google Scholar On the other hand, most dog dander (personal communication, ALK Laboratories, July 2006), cockroach,23Patterson M.L. Slater J.E. Characterization and comparison of commercially available German and American cockroach allergen extracts.Clin Exp Allergy. 2002; 32: 721-727Crossref PubMed Scopus (66) Google ScholarAlternaria, and Aspergillus24Vailes L. Sridhara S. Cromwell O. Weber B. Breitenbach M. Chapman M. Quantitation of the major fungal allergens, Alt a 1 and Asp f 1, in commercial_allergenic products.J Allergy Clin Immunol. 2001; 107: 641-646Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar extracts are quite low in major allergen content and, when tested, in overall allergenic potency.Table IImmunotherapy dosing by major allergen contentAllergen extractMajor allergenEffective dosingLess effective or ineffective dosingShort ragweedAmb a 165Creticos P.S. Adkinson N.F. Sobotka A. Proud D. Meier H.L. Naclerio R.M. et al.Nasal challenge with ragweed pollen in hay fever patients: effect of immunotherapy.J Clin Invest. 1985; 76: 2247-2253Crossref PubMed Scopus (181) Google Scholar to 246Furin M.J. Norman P.S. Creticos P.S. Proud D. Sobotka A. Lichtenstein L.M. Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity.J Allergy Clin Immunol. 1991; 88: 27-32Abstract Full Text PDF PubMed Scopus (164) Google Scholar μg0.67Creticos P.S. Marsh D.G. Proud D. Sobotka A. Adkinson N.F. Friedhoff L. Responses to ragweed-pollen nasal challenge before and after immunotherapy.J Allergy Clin Immunol. 1989; 84: 197-205Abstract Full Text PDF PubMed Scopus (96) Google Scholar and 26Furin M.J. Norman P.S. Creticos P.S. Proud D. Sobotka A. Lichtenstein L.M. Immunotherapy decreases antigen-induced eosinophil cell migration into the nasal cavity.J Allergy Clin Immunol. 1991; 88: 27-32Abstract Full Text PDF PubMed Scopus (164) Google Scholar μgTimothyPhl p 5158Frew A.J. Powell R.J. Corrigan C.J. Durham S.R. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 319-328Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar & 209Varney V.A. Edwards J. Tabbah K. Brewster H. Mavroleon G. Frew A.J. Clinical efficacy of specific immunotherapy to cat dander: a double-blind, placebo-controlled trial.Clin Exp Allergy. 1997; 27: 860-867Crossref PubMed Scopus (156) Google Scholar μg28Frew A.J. Powell R.J. Corrigan C.J. Durham S.R. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis.J Allergy Clin Immunol. 2006; 117: 319-328Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar μgBirchBet v 13.2810Khinchi M.S. Poulsen L.K. Carat F. Andre C. Hansen A.B. Malling H.J. Clinical efficacy of sublingual and subcutaneous Birch pollen allergen specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study.Allergy. 2004; 59: 45-53Crossref PubMed Scopus (219) Google Scholar & 1211Rak S. Heinrich C. Schevnius A. Comparison of nasal immunohistology in patients with seasonal rhinoconjunctivitis treated with topical steroids or specific allergen immunotherapy.Allergy. 2005; 60: 643-649Crossref PubMed Scopus (10) Google Scholar μgNDDermatophagoides pteronyssinusDer p 1712Olaquibel J.M. Tabar A.I. Garcia B.E. Martin S. Rico P. Long-term immunotherapy with an optimal maintenance dose of a standardized Dermatophagoides pteronyssinus extract in asthmatic patients.J Investig Allergol Clin Immunol. 1999; 9: 110-116PubMed Google Scholar & 1213Ewan P.W. Alexander M.M. Snape C. Ind P.W. Agrell B. Dreborg S. Effective hyposensitization in allergic rhinitis using a potent partially purified extract of house dust mite.Clin Allergy. 1988; 18: 501-508Crossref PubMed Scopus (106) Google Scholar μg0.714Haugaard L. Dahl R. Jacobsen L. A controlled dose-response study of immunotherapy with standardized, partially purified extract of house dust mite: clinical efficacy and side effects.J Allergy Clin Immunol. 1993; 91: 709-722Abstract Full Text PDF PubMed Scopus (194) Google Scholar μgDermatophagoides farinaeDer f 11015Olsen O.T. Larsen K.R. Jacobsen L. Svendsen U.G. A 1-year, placebo-controlled, double-blind house-dust-mite immunotherapy study in asthmatic adults.Allergy. 1997; 52: 853-859Crossref PubMed Scopus (97) Google Scholar μgNDCat danderFel d 11116Alvarez-Cuesta E. Cuesta-Herranz J. Puyana-Ruiz J. Cuesta-Herranz C. Blanco-Quiros A. Monoclonal antibody-standardized cat immunotherapy: risk benefit effects from a double-blind study.J Allergy Clin Immunol. 1994; 93: 556-566Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar-1717Hedlin J.G. Lonnevig V. Heilbron H. Lilja G. Norrlind K. Pegelow K. Immunotherapy with cat- and dog-dander extracts, V: effects of 3 years of treatment.J Allergy Clin Immunol. 1991; 87: 955-964Abstract Full Text PDF PubMed Scopus (132) Google Scholar μg0.618Ewbank P.A. Murray J. Sanders K. Curran-Everett D. Dreskin S. Nelson H.S. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract.J Allergy Clin Immunol. 2003; 111: 155-161Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 19Nanda A. O'Connor M. Anand M. Dreskin S.C. Zhang L. Hines B. et al.Dose dependence and time course of the immunologic response to administration of standardized cal allergen extract.J Allergy Clin Immunol. 2004; 114: 1339-1344Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar and 3 μg18Ewbank P.A. Murray J. Sanders K. Curran-Everett D. Dreskin S. Nelson H.S. A double-blind, placebo-controlled immunotherapy dose-response study with standardized cat extract.J Allergy Clin Immunol. 2003; 111: 155-161Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar, 19Nanda A. O'Connor M. Anand M. Dreskin S.C. Zhang L. Hines B. et al.Dose dependence and time course of the immunologic response to administration of standardized cal allergen extract.J Allergy Clin Immunol. 2004; 114: 1339-1344Abstract Full Text Full Text PDF PubMed Scopus (117) Google ScholarDog danderCan f 11520Lent A. Harbeck R. Strand M. Sills M. Schmidt K. Efaw B. et al.Immunological response to administration of standardized dog allergen extract at differing doses.J Allergy Clin Immunol. 2006; 118: 1249-1256Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar μg0.620Lent A. Harbeck R. Strand M. Sills M. Schmidt K. Efaw B. et al.Immunological response to administration of standardized dog allergen extract at differing doses.J Allergy Clin Immunol. 2006; 118: 1249-1256Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar & 320Lent A. Harbeck R. Strand M. Sills M. Schmidt K. Efaw B. et al.Immunological response to administration of standardized dog allergen extract at differing doses.J Allergy Clin Immunol. 2006; 118: 1249-1256Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar μgAlternariaAlt a 11.621Horst M. Hejjaoui A. Horst V. Michel F.-B. Bousquet J. Double-blind, placebo-controlled rush immunotherapy with a standardized Alternaria extract.J Allergy Clin Immunol. 1990; 85: 460-472Abstract Full Text PDF PubMed Scopus (213) Google Scholar μgNDND, Not determined. Open table in a new tab Table IIMajor allergen content: US standardized and unstandardized extractsExtractExpressed concentrationMajor allergenMean major allergen contentShort ragweed∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.1:10 wt/volAmb a 1424 μg/mLTimothy grass∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.100,000 BAU/mLPhl p 5680 μg/mLKentucky blue grass∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.100,000 BAU/mLGroup 5300 μg/mLOrchard grass∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.100,000 BAU/mLGroup 5750 μg/mLBermuda grass∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.10,000 BAU/mLGroup 1300 μg/mLDermatophagoides pteronyssinus∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.10,000 AU/mLDer p 176 μg/mLDermatophagoides farinae∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.10,000 AU/mLDer f 156 μg/mLCat dander∗Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.10,000 BAU/mLFel d 143 μg/mLAP dog dander†Personal communication, Hollister-Stier Laboratories, Spokane, Wash, November 2006.1:100 wt/volCan f 1180 μg/mLAP, Acetone precipitated (product of Hollister-Stier Laboratories, Spokane, Wash); AU, allergy units; BAU, bioequivalent allergy units.∗ Personal communication, ALK Laboratories, Round Rock, Tex, July 2006.† Personal communication, Hollister-Stier Laboratories, Spokane, Wash, November 2006. Open table in a new tab Table IIIEffective dosing with US extractsExtractMajor allergen dose requiredAdd to 10 mL vial, assuming 0.5-mL maintenance injectionTimothy grass20 μg Phl p 50.6 mL 100,000 BAU/mLShort ragweed12 μg Amb a 10.8 mL 1:10 wt/volDermatophagoides pteronyssinus7 μg Der p 12.2 mL 10,000 AU/mLDermatophagoides farinae10 μg Der f 13.3 mL 10,000 AU/mLCat dander15 μg Fel d 16 mL 10,000 BAU/mLDog dander15 μg Can f 12.1 mL 1:100 wt/vol AP dog (Hollister-Stier Laboratories)AP, Acetone precipitated; AU, allergy units; BAU, bioequivalent allergy units. Open table in a new tab Prevention of disease progressionAlthough the clinical response to immunotherapy has been proven to be allergen-specific,25Lowell F.C. Franklin W. A double-blind study of the effectiveness and specificity of injection therapy in ragweed hay fever.N Engl J Med. 1965; 273: 675-679Crossref PubMed Scopus (197) Google Scholar, 26Norman P.S. Lichtenstein L.M. The clinical and immunologic specificity of immunotherapy.J Allergy Clin Immunol. 1978; 61: 370-377Abstract Full Text PDF PubMed Scopus (90) Google Scholar there is now good evidence that administration of appropriate monotherapy to monosensitized patients can reduce the likelihood of the patients developing additional sensitivities.27Des Roches A. Paradis L. Menardo J.-L. Bouges S. Daures J.-P. Bousquet J. Immunotherapy with a standardized Dermatophagoides pteronyssinus extract, VI: specific immunotherapy prevents the onset of new sensitizations in children.J Allergy Clin Immunol. 1997; 99: 450-453Abstract Full Text Full Text PDF PubMed Scopus (589) Google Scholar, 28Pajno G.B. Barberio G. De Luca F. Morabito L. Parmiani S. Prevention of new sensitization in asthmatic children monosensitized to house dust mite by specific immunotherapy: a six-year, follow-up study.Clin Exp Allergy. 2001; 31: 1392-1397Crossref PubMed Scopus (539) Google Scholar, 29Purello-D'Ambrosio F. Gangemi S. Merendino R.A. Isola S. Puccinelli P. Parmiani S. et al.Prevention of new sensitization in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study.Clin Exp Allergy. 2001; 31: 1295-1302Crossref PubMed Scopus (278) Google Scholar In the 2 largest studies,28Pajno G.B. Barberio G. De Luca F. Morabito L. Parmiani S. Prevention of new sensitization in asthmatic children monosensitized to house dust mite by specific immunotherapy: a six-year, follow-up study.Clin Exp Allergy. 2001; 31: 1392-1397Crossref PubMed Scopus (539) Google Scholar, 29Purello-D'Ambrosio F. Gangemi S. Merendino R.A. Isola S. Puccinelli P. Parmiani S. et al.Prevention of new sensitization in monosensitized subjects submitted to specific immunotherapy or not: a retrospective study.Clin Exp Allergy. 2001; 31: 1295-1302Crossref PubMed Scopus (278) Google Scholar the likelihood of developing additional positive skin tests was reduced from about 2/3 to 1/4, and further, the protection was shown to persist 3 years after the 3-year to 4-year course of specific immunotherapy was completed.Three years of immunotherapy with birch and/or timothy in children with only seasonal allergic rhinitis was found to reduce the likelihood of their developing asthma by a factor of approximately 2.5.30Moller C. Dreborg S. Ferdousi H.A. Halken S. Host A. Jacobsen L. et al.Pollen immunotherapy reduces he development of asthma in children with seasonal rhinoconjunctivitis (the PAT Study).J Allergy Clin Immunol. 2002; 109: 251-256Abstract Full Text Full Text PDF PubMed Scopus (994) Google Scholar Follow-up reports 231Niggemann B. Jacobsen L. Dreborg S. Ferdousi H.A. Halken S. Host A. et al.Five-year follow-up on the PAT study: specific immunotherapy and long term prevention of asthma in children.Allergy. 2006; 61: 855-859Crossref PubMed Scopus (292) Google Scholar and 732Valovirta E. Jacobsen L. Niggemann B. Dreborg S. Ferdousi H. Halken S. et al.A 3-year course of subcutaneous specific immunotherapy results in long-term prevention of asthma in children: ten-year follow-up on the PAT-Study.J Allergy Clin Immunol. 2006; 117 ([abstract]): 721Abstract Full Text Full Text PDF Google Scholar years after stopping immunotherapy have shown persistence of the reduced risk for developing asthma.Persistence of effect after discontinuationGiven the persistence of the protective effect after discontinuing immunotherapy on the development of new sensitizations and progression to asthma, it is not surprising that there is also persistence of reduction of clinical symptoms.33Ebner C. Kraft D. Ebner H. Booster immunotherapy (IT).Allergy. 1994; 49: 38-42Crossref PubMed Scopus (30) Google Scholar, 34Des Roches A. Paradis L. Knani J. Hejjaoui A. Dhivert H. Chanez P. et al.Immunotherapy with a standardized Dermatophagoides pteronyssinus extract, V: duration of the efficacy of immunotherapy after its cessation.Allergy. 1996; 51: 430-433PubMed Google Scholar, 35Durham S.R. Walker S.M. Varga E.-M. Jacobson M.R. O'Brien F. Noble W. et al.Long-term clinical efficacy of grass pollen immunotherapy.N Engl J Med. 1999; 344: 468-475Crossref Scopus (1246) Google Scholar This has been shown most convincingly by a double-blind study in which subjects who had received 3 or 4 years of timothy grass immunotherapy were randomized to continue receiving monthly maintenance injections of grass extract or to receive placebo injections.35Durham S.R. Walker S.M. Varga E.-M. Jacobson M.R. O'Brien F. Noble W. et al.Long-term clinical efficacy of grass pollen immunotherapy.N Engl J Med. 1999; 344: 468-475Crossref Scopus (1246) Google Scholar After 3 more years, there was no difference in control of symptoms or medication use between the 2 groups.Concerns and controversiesImmunotherapy for atopic dermatitis and food allergyThere have been a number of uncontrolled studies reporting improvement in atopic dermatitis with allergen immunotherapy.36Werfel T. Breuer K. Rueff F. Przybilla B. Worm M. Grewe M. et al.Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.Allergy. 2006; 61: 202-205Crossref PubMed Scopus (241) Google Scholar Recently, a double-blind study of injection immunotherapy was conducted in 89 adults with chronic atopic dermatitis and sensitivity to house dust mites.36Werfel T. Breuer K. Rueff F. Przybilla B. Worm M. Grewe M. et al.Usefulness of specific immunotherapy in patients with atopic dermatitis and allergic sensitization to house dust mites: a multi-centre, randomized, dose-response study.Allergy. 2006; 61: 202-205Crossref PubMed Scopus (241) Google Scholar Maintenance doses of 20, 2000, and 20,000 standardized quality units were given weekly for 1 year. The top dose was 1/5 the customary maintenance dose for treating allergic respiratory diseases; the lowest dose could be considered a placebo. Fifty-one subjects completed the study, with those receiving the 2 higher doses showing significant reduction in symptom scores and topical steroid use.Injection immunotherapy has also been tried for food allergy. Although patients with anaphylactic sensitivity to peanuts could tolerate larger doses of peanuts when they were receiving injections of peanut extract, the frequency of systemic reactions to the injections proved unacceptable.37Nelson H.S. Lahr J. Rule R. Bock A. Leung D. Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract.J Allergy Clin Immunol. 1997; 99: 744-751Abstract Full Text PDF PubMed Scopus (504) Google Scholar However, in 3 studies, SCIT for birch allergy reduced symptoms of the oral allergy syndrome caused by eating apples.38Bucher X. Pichler W.J. Dahinden C.A. Helbling A. Effect of tree pollen specific subcutaneous immunotherapy on the oral allergy syndrome to apple and hazelnut.Allergy. 2004; 59: 1272-1276Crossref PubMed Scopus (137) Google Scholar, 39Bolhaar S.T.H.P. Tiemessen M.M. Zuidmeer I. van Leeuwen A. Hoffmann-Sommergruber K. Bruijnzeel-Koomen C.A.F.M. et al.Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind foo
Referência(s)