АЛЛЕРГЕН-СПЕЦИФИЧЕСКАЯ ИММУНОТЕРАПИЯ: ЭФФЕКТИВНОСТЬ, ПРОДОЛЖИТЕЛЬНОСТЬ, МЕТОДЫ И ФАРМАКОЭКОНОМИКА
- Авторы: Уоллес Д1
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Учреждения:
- Современная Школа медицины Юго-Восточного Университета, Форт-Лодердейл, Флорида, США
- Выпуск: Том 22, № 3 (2018)
- Страницы: 288-301
- Раздел: АЛЛЕРГОЛОГИЯ. ДЕРМАТОЛОГИЯ
- URL: https://journals.rudn.ru/medicine/article/view/19679
- DOI: https://doi.org/10.22363/2313-0245-2018-22-3-288-301
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Аннотация
Несмотря на то, что аллерген-специфическая иммунотерапия (АСИТ) более ста лет применяется для лечения аллергического ринита (АР), аллергического конъюнктивита, астмы, атопического дерматита и гиперчувствительности к укусам насекомых, она постепенно достигла всеобщего признания. С опубликованием в 1998 году «Позиционного документа Всемирной организации здравоохранения аллерген-специфической иммунотерапии», в котором обобщены научные данные об эффективности и долгосрочной пользе этого способа терапии, аллерген-специфическая иммунотерапия стала признанной и уважаемой формой лечения. В обзоре обсуждаются следующие темы аллерген-специфической иммунотерапии: причины рекомендации по терапии АСИТ, механизм действия, подкожные и сублингвальные методы применения, продолжительность лечения, соблюдение пациентом назначений врача и экономическая эффективность. Особое внимание уделяется необходимости поддерживать, а не обвинять пациента в несоблюдении назначений врача, поскольку пациент, врач и система здравоохранения в целом должны заботиться о создании среды, в которой пациент будет неукоснительно соблюдать назначения врача. Несоблюдение пациентом назначений врача является следствием большого количества факторов, и врач должен учитывать все факторы с целью обеспечения соблюдения пациентом всех рекомендаций. Желание пациента соблюдать назначения врача необходимо рассматривать в динамике с целью выбора наилучшего времени для начала АСИТ, также необходимо обеспечить наблюдение за пациентом в течение нескольких лет после проведенной АСИТ. Пациент, неукоснительно исполняющий назначения врача в первый год лечения, не сможет быть столь же последовательным на третьем году терапии без дополнительной поддержки. Система здравоохранения и профессиональные организации должны помочь в обучении врачей эффективным и точным способам оценки причин несоблюдения пациентами назначений врача и осуществления мер по оптимизации приверженности пациентов к лечению на продолжении длительного срока. Междисциплинарный подход к решению этой проблемы потребует участия медицинских работников, исследователей, профессиональных организаций, страховых компаний и лиц, определяющих политику в сфере здравоохранения.
Об авторах
Д Уоллес
Современная Школа медицины Юго-Восточного Университета, Форт-Лодердейл, Флорида, США
Email: drdanawallace@gmail.com
Список литературы
- Bousquet J, Lockey R, Malling HJ, Alvarez-Cuesta E, Canonica GW, Chapman MD, et al. Allergen immunotherapy: therapeutic vaccines for allergic diseases. World Health Organization. American academy of Allergy, Asthma and Immunology. Ann Allergy Asthma Immunol. 1998;81[5]:401-5.
- Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma [ARIA] 2008 update [in collaboration with the World Health Organization, GA[2]LEN and AllerGen]. Allergy. 2008;63 Suppl 86:8-160.
- Dhami S, Nurmatov U, Arasi S, Khan T, Asaria M, Zaman H, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta-analysis. Allergy. 2017;72[11]:1597-631.
- Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998; 102[4 Pt 1]:558-62.
- Burks AW, Calderon MA, Casale T, Cox L, Demoly P, Jutel M, et al. Update on allergy immunotherapy: American Academy of Allergy, Asthma & Immunology/European Academy of Allergy and Clinical Immunology/PRACTALL consensus report. J Allergy Clin Immunol. 2013;131[5]:1288-96 e3.
- Ponda P, Mithani S, Kopyltsova Y, Sison C, Gupta P, Larenas D, et al. Allergen immunotherapy practice patterns: a worldwide survey. Ann Allergy Asthma Immunol. 2012;108[6]:454-9 e7.
- Kim JM, Lin SY, Suarez-Cuervo C, Chelladurai Y, Ramanathan M, Segal JB, et al. Allergen-specific immunotherapy for pediatric asthma and rhinoconjunctivitis: a systematic review. Pediatrics. 2013;131[6]:1155-67.
- Lin SY, Erekosima N, Suarez-Cuervo C, Ramanathan M, Kim JM, Ward D, et al. AHRQ Comparative Effectiveness Reviews. Allergen-Specific Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and/or Asthma: Comparative Effectiveness Review. Rockville [MD]: Agency for Healthcare Research and Quality [US]; 2013.
- Senna G, Ridolo E, Calderon M, Lombardi C, Canonica GW, Passalacqua G. Evidence of adherence to allergen-specific immunotherapy. Curr Opin Allergy Clin Immunol. 2009;9[6]:544-8.
- Canonica GW, Bousquet J, Casale T, Lockey RF, Baena-Cagnani CE, Pawankar R, et al. Sub-lingual immunotherapy: World Allergy Organization Position Paper 2009. Allergy. 2009;64 Suppl 91:1-59.
- Halken S, Larenas-Linnemann D, Roberts G, Calderon MA, Angier E, Pfaar O, et al. EAACI guidelines on allergen immunotherapy: Prevention of allergy. Pediatr Allergy Immunol. 2017;28[8]:728-45.
- Dhami S, Kakourou A, Asamoah F, Agache I, Lau S, Jutel M, et al. Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis. Allergy. 2017;72[12]:1825-48.
- Nurmatov U, Dhami S, Arasi S, Roberts G, Pfaar O, Muraro A, et al. Allergen immunotherapy for allergic rhinoconjunctivitis: a systematic overview of systematic reviews. Clin Transl Allergy. 2017;7:24.
- Meadows A, Kaambwa B, Novielli N, Huissoon A, Fry-Smith A, Meads C, et al. A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis. Health Technol Assess. 2013; 17[27]:vi, xi-xiv, 1-322.
- Kristiansen M, Dhami S, Netuveli G, Halken S, Muraro A, Roberts G, et al. Allergen immunotherapy for the prevention of allergy: A systematic review and meta-analysis. Pediatr Allergy Immunol. 2017;28[1]:18-29.
- Roberts G, Pfaar O, Akdis CA, Ansotegui IJ, Durham SR, Gerth van Wijk R, et al. EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis. Allergy. 2018;73[4]:765-98.
- Eng PA, Borer-Reinhold M, Heijnen IA, Gnehm HP. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy. 2006;61[2]:198-201.
- Jutel M, Agache I, Bonini S, Burks AW, Calderon M, Canonica W, et al. International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics. J Allergy Clin Immunol. 2016; 137[2]:358-68.
- Tworek D, Bochenska-Marciniak M, Kuprys-Lipinska I, Kupczyk M, Kuna P. Perennial is more effective than preseasonal subcutaneous immunotherapy in the treatment of seasonal allergic rhinoconjunctivitis. Am J Rhinol Allergy. 2013;27[4]:304-8.
- Esch RE. Specific immunotherapy in the U.S.A.: general concept and recent initiatives. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M. 2003[94]:17-22; discussion 3.
- Cox L, Jacobsen L. Comparison of allergen immunotherapy practice patterns in the United States and Europe. Ann Allergy Asthma Immunol. 2009;103[6]:451-59; quiz 9-61, 95.
- Pfaar O, Biedermann T, Klimek L, Sager A, Robinson DS. Depigmented-polymerized mixed grass/birch pollen extract immunotherapy is effective in polysensitized patients. Allergy. 2013;68[10]:1306-13.
- Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, et al. Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy. J Allergy Clin Immunol. 2012;130[1]:215-24 e7.
- Amar SM, Harbeck RJ, Sills M, Silveira LJ, O'Brien H, Nelson HS. Response to sublingual immunotherapy with grass pollen extract: monotherapy versus combination in a multiallergen extract. J Allergy Clin Immunol. 2009; 124[1]:150-6 e1-5.
- Lowell FC, Franklin W. A double-blind study of the effectiveness and specificity of injecton therapy in ragweed hay fever. N Engl J Med. 1965;273[13]:675-9.
- Franklin W, Lowell FC. Comparison of two dosages of ragweed extract in the treatment of pollenosis. JAMA. 1967;201[12]:915-7.
- Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children - a 14-year study. Pediatrics. 1968;42[5]:793-802.
- Bousquet J, Becker WM, Hejjaoui A, Chanal I, Lebel B, Dhivert H, et al. Differences in clinical and immunologic reactivity of patients allergic to grass pollens and to multiple-pollen species. II. Efficacy of a double-blind, placebo-controlled, specific immunotherapy with standardized extracts. J Allergy Clin Immunol. 1991;88[1]:43-53.
- Adkinson NF, Jr., Eggleston PA, Eney D, Goldstein EO, Schuberth KC, Bacon JR, et al. A controlled trial of immunotherapy for asthma in allergic children. N Engl J Med. 1997;336[5]:324-31.
- Durham SR, investigators GT. Sustained effects of grass pollen AIT. Allergy. 2011;66 Suppl 95:50-2.
- Durham SR, Emminger W, Kapp A, de Monchy JG, Rak S, Scadding GK, 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]:717-25 e5.
- Marogna M, Spadolini I, Massolo A, Canonica GW, Passalacqua G. Long-lasting effects of sublingual immunotherapy according to its duration: a 15-year prospective study. J Allergy Clin Immunol. 2010;126[5]:969-75.
- Frati F, Dell'Albani I, Incorvaia C. Long-term efficacy of allergen immunotherapy: what do we expect? Immunotherapy. 2013;5[2]:131-3.
- Durham SR, Walker SM, Varga EM, Jacobson MR, O'Brien F, Noble W, et al. Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med. 1999; 341[7]:468-75.
- Des 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[6]:430-3.
- Incorvaia C, Riario-Sforza GG, Incorvaia S, Frati F. Sublingual immunotherapy in allergic asthma: Current evidence and needs to meet. Ann Thorac Med. 2010; 5[3]:128-32.
- Cox L, Cohn JR. Duration of allergen immunotherapy in respiratory allergy: when is enough, enough? Ann Allergy Asthma Immunol. 2007;98[5]:416-26.
- Brehler R, Klimek L, Kopp MV, Christian Virchow J. Specific immunotherapy-indications and mode of action. Dtsch Arztebl Int. 2013;110[9]:148-58.
- Anolik R, Schwartz AM, Sajjan S, Allen-Ramey F. Patient initiation and persistence with allergen immunotherapy. Ann Allergy Asthma Immunol. 2014;113[1]: 101-7.
- Allam JP, Andreasen JN, Mette J, Serup-Hansen N, Wustenberg EG. Comparison of allergy immunotherapy medication persistence with a sublingual immunotherapy tablet versus subcutaneous immunotherapy in Germany. J Allergy Clin Immunol. 2018;141[5]:1898-901 e5.
- Egert-Schmidt AM, Kolbe JM, Mussler S, Thum-Oltmer S. Patients' compliance with different administration routes for allergen immunotherapy in Germany. Patient Prefer Adherence. 2014;8:1475-81.
- Hsu NM, Reisacher WR. A comparison of attrition rates in patients undergoing sublingual immunotherapy vs subcutaneous immunotherapy. Int Forum Allergy Rhinol. 2012;2[4]:280-4.
- Kiel MA, Roder E, Gerth van Wijk R, Al MJ, Hop WC, Rutten-van Molken MP. Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy. J Allergy Clin Immunol. 2013; 132[2]:353-60 e2.
- Leader BA, Rotella M, Stillman L, DelGaudio JM, Patel ZM, Wise SK. Immunotherapy compliance: comparison of subcutaneous versus sublingual immunotherapy. Int Forum Allergy Rhinol. 2016;6[5]:460-4.
- Lemberg ML, Berk T, Shah-Hosseini K, Kasche EM, Mosges R. Sublingual versus subcutaneous immunotherapy: patient adherence at a large German allergy center. Patient Prefer Adherence. 2017;11:63-70.
- Pajno GB, Vita D, Caminiti L, Arrigo T, Lombardo F, Incorvaia C, et al. Children's compliance with allergen immunotherapy according to administration routes. J Allergy Clin Immunol. 2005;116[6]:1380-1.
- Sieber J, De Geest S, Shah-Hosseini K, Mosges R. Medication persistence with long-term, specific grass pollen immunotherapy measured by prescription renewal rates. Curr Med Res Opin. 2011;27[4]:855-61.
- Calderon MA, Cox L, Casale TB, Mosges R, Pfaar O, Malling HJ, et al. The effect of a new communication template on anticipated willingness to initiate or resume allergen immunotherapy: an internet-based patient survey. Allergy Asthma Clin Immunol. 2015;11[1]:17.
- Sabate E. Adherence to Long-Term Therapies: Evidence for Action. Geneva, Switzerland; 2003.
- Denford S, Frost J, Dieppe P, Cooper C, Britten N. Individualisation of drug treatments for patients with long-term conditions: a review of concepts. BMJ Open. 2014;4[3]:e004172.
- Costa E, Giardini A, Savin M, Menditto E, Lehane E, Laosa O, et al. Interventional tools to improve medication adherence: review of literature. Patient Prefer Adherence. 2015;9:1303-14.
- Ho PM, Magid DJ, Masoudi FA, McClure DL, Rumsfeld JS. Adherence to cardioprotective medications and mortality among patients with diabetes and ischemic heart disease. BMC Cardiovasc Disord. 2006;6:48.
- Krishnan JA, Bender BG, Wamboldt FS, Szefler SJ, Adkinson NF, Jr., Zeiger RS, et al. Adherence to inhaled corticosteroids: an ancillary study of the Childhood Asthma Management Program clinical trial. J Allergy Clin Immunol. 2012;129[1]:112-8.
- Huetsch JC, Uman JE, Udris EM, Au DH. Predictors of adherence to inhaled medications among Veterans with COPD 2012 [updated NovPMC3475808]. 2012/07/12: [1506-12]. Available from: https://www.ncbi.nlm.nih.gov/ pubmed/22782274.
- Lamkin M, Elliott C. Curing the Disobedient Patient: Mediction Adherence Programs as Pharmaceutical Marketing Tools 2014 [Available from: https://digitalcommons. law.utulsa.edu/fac_pub/475.
- Institute NEH. Thinking outside the pillbox: a system-wide approach to improving patient medication adherence for chronic disease. 2009 [Available from: https://www.nehi.net/writable/publication_files/file/pa_ issue_brief_final.pdf.
- Cutler RL, Fernandez-Llimos F, Frommer M, Benrimoj C, Garcia-Cardenas V. Economic impact of medication non-adherence by disease groups: a systematic review. BMJ Open. 2018;8[1]:e016982.
- Lamkin M, Elliott C. Curing the disobedient patient: medication adherence programs as pharmaceutical marketing tools. J Law Med Ethics. 2014;42[4]:492-500.
- Senna G, Lombardi C, Canonica GW, Passalacqua G. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers' viewpoint. J Allergy Clin Immunol. 2010;126[3]:668-9.
- Rhodes BJ. Patient dropouts before completion of optimal dose, multiple allergen immunotherapy. Ann Allergy Asthma Immunol. 1999;82[3]:281-6.
- Kiotseridis H, Arvidsson P, Backer V, Braendholt V, Tunsater A. Adherence and quality of life in adults and children during 3-years of SLIT treatment with Grazax-a real life study. NPJ primary care respiratory medicine. 2018;28[1]:4.
- Hankin CS, Cox L, Lang D, Levin A, Gross G, Eavy G, et al. Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis: patterns of care, resource use, and costs. J Allergy Clin Immunol. 2008;121[1]: 227-32.
- Savi E, Peveri S, Senna G, Passalacqua G. Causes of SLIT discontinuation and strategies to improve the adherence: a pragmatic approach. Allergy. 2013;68[9]: 1193-5.
- Vita D, Caminiti L, Ruggeri P, Pajno GB. Sublingual immunotherapy: adherence based on timing and monitoring control visits. Allergy. 2010;65[5]:668-9.
- Epstein TE, Tankersley MS. Are Allergen Immunotherapy Dose Adjustments Needed for Local Reactions, Peaks of Season, or Gaps in Treatment? J Allergy Clin Immunol Pract. 2017;5[5]:1227-33.
- Wong PH, Quinn JM, Gomez RA, Webb CN. Systemic reactions to immunotherapy during mountain cedar season: implications for seasonal dose adjustment. J Allergy Clin Immunol Pract. 2017;5[5]:1438-9 e1.
- Brehler R, Klimek L, Pfaar O, Hauswald B, Worm M, Bieber T. Safety of a rush immunotherapy build-up schedule with depigmented polymerized allergen extracts. Allergy Asthma Proc. 2010;31[3]:e31-8.
- Cardona R, Lopez E, Beltran J, Sanchez J. Safety of immunotherapy in patients with rhinitis, asthma or atopic dermatitis using an ultra-rush buildup. A retrospective study. Allergol Immunopathol [Madr]. 2014;42[2]:90-5.
- Casanovas M, Martin R, Jimenez C, Caballero R, Fernandez-Caldas E. Safety of an ultra-rush immunotherapy build-up schedule with therapeutic vaccines containing depigmented and polymerized allergen extracts. Int Arch Allergy Immunol. 2006;139[2]:153-8.
- Pfaar O, Mosges R, Hormann K, Klimek L. Safety aspects of Cluster immunotherapy with semi-depot allergen extracts in seasonal allergic rhinoconjunctivitis. Eur Arch Otorhinolaryngol. 2010;267[2]:245-50.
- More DR, Hagan LL. Factors affecting compliance with allergen immunotherapy at a military medical center. Ann Allergy Asthma Immunol. 2002;88[4]:391-4.
- Carlson GS, Wong PH, White KM, Quinn JM. Evaluation of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy in immunotherapy-associated systemic reactions. J Allergy Clin Immunol Pract. 2017;5[5]:1430-2.
- Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allergen immunotherapy: a practice parameter third update. J Allergy Clin Immunol. 2011; 127[1 Suppl]:S1-55.
- Lim CE, Sison CP, Ponda P. Comparison of Pediatric and Adult Systemic Reactions to Subcutaneous Immunotherapy. J Allergy Clin Immunol Pract. 2017;5[5]: 1241-7 e2.
- Comberiati P, Marseglia GL, Barberi S, Passalacqua G, Peroni DG. Allergen-Specific Immunotherapy for Respiratory Allergy in Children: Unmet Needs and Future Goals. J Allergy Clin Immunol Pract. 2017;5[4]:946-50.
- Jonasson G, Carlsen KH, Mowinckel P. Asthma drug adherence in a long term clinical trial. Arch Dis Child. 2000;83[4]:330-3.
- Bousquet J, Hellings PW, Agache I, Bedbrook A, Bachert C, Bergmann KC, et al. ARIA 2016: Care pathways implementing emerging technologies for predictive medicine in rhinitis and asthma across the life cycle. Clin Transl Allergy. 2016;6:47.
- May JR, Dolen WK. Management of Allergic Rhinitis: A Review for the Community Pharmacist. Clin Ther. 2017;39[12]:2410-9.
- Jansen A, Andersen KF, Bruning H. Evaluation of a compliance device in a subgroup of adult patients receiving specific immunotherapy with grass allergen tablets [GRAZAX] in a randomized, open-label, controlled study: an a priori subgroup analysis. Clin Ther. 2009; 31[2]:321-7.
- Rand CS, Wise RA. Measuring adherence to asthma medication regimens. Am J Respir Crit Care Med. 1994; 149[2 Pt 2]:S69-76; discussion S7-8.
- DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42[3]:200-9.
- Bender BG. Can health care organizations improve health behavior and treatment adherence? Popul Health Manag. 2014;17[2]:71-8.
- ACAAI. New toolkit helps patients understand immunotherapy choices 2017 [cited 2018 Aug 19]. Available from: https://college.acaai.org/publications/college-insider/ new-toolkit-helps-patients-understand-immunotherapy-choices.
- Borrelli B, Riekert KA, Weinstein A, Rathier L. Brief motivational interviewing as a clinical strategy to promote asthma medication adherence. J Allergy Clin Immunol. 2007;120[5]:1023-30.
- Lockey RF, Hankin CS. Health economics of allergen-specific immunotherapy in the United States. J Allergy Clin Immunol. 2011;127[1]:39-43.
- Hankin CS, Cox L, Bronstone A. The health economics of allergen immunotherapy. Immunology and allergy clinics of North America. 2011;31[2]:325-41, x.
- Hankin CS, Cox L. Allergy immunotherapy: what is the evidence for cost saving? Curr Opin Allergy Clin Immunol. 2014;14[4]:363-70.
- Canonica GW, Passalacqua G. Disease-modifying effect and economic implications of sublingual immunotherapy. J Allergy Clin Immunol. 2011;127[1]:44-5.
- Hankin CS, Cox L, Lang D, Bronstone A, Fass P, Leatherman B, et al. Allergen immunotherapy and health care cost benefits for children with allergic rhinitis: a large-scale, retrospective, matched cohort study. Ann Allergy Asthma Immunol. 2010;104[1]:79-85.
- Hankin CS, Cox L, Bronstone A, Wang Z. Allergy immunotherapy: reduced health care costs in adults and children with allergic rhinitis. J Allergy Clin Immunol. 2013;131[4]:1084-91.
- Allen-Ramey F, Mao J, Blauer-Peterson C, Rock M, Nathan R, Halpern R. Healthcare costs for allergic rhinitis patients on allergy immunotherapy: a retrospective observational study. Curr Med Res Opin. 2017;33[11]: 2039-47.
- Ariano R, Berto P, Tracci D, Incorvaia C, Frati F. Pharmacoeconomics of allergen immunotherapy compared with symptomatic drug treatment in patients with allergic rhinitis and asthma. Allergy Asthma Proc. 2006;27[2]: 159-63.
- Petersen KD, Gyrd-Hansen D, Dahl R. Health-economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy. Allergol Immunopathol [Madr]. 2005;33[6]:296-302.
- Pokladnikova J, Krcmova I, Vlcek J. Economic evaluation of sublingual vs subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol. 2008;100[5]:482-9.
- Bachert C, Vestenbaek U, Christensen J, Griffiths UK, Poulsen PB. Cost-effectiveness of grass allergen tablet [GRAZAX] for the prevention of seasonal grass pollen induced rhinoconjunctivitis - a Northern European perspective. Clin Exp Allergy. 2007;37[5]:772-9.
- Schadlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics. 2000;17[1]: 37-52.