A systematic review and economic evaluation of subcutaneous and sublingual allergen immunotherapy in adults and children with seasonal allergic rhinitis

Health Technology Assessment

Volumn 17, Issue 27, 2013, Pages

  Meadows, A ^a   Kaambwa, B ^a   Novielli, N ^a   Huissoon, A ^b   Fry Smith, A ^a   Meads, C ^c   Barton, P ^a   Dretzke, J ^a  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b BIRMINGHAM HEARTLANDS HOSPITAL   (United Kingdom)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADRENALIN; ALLERGEN; ALLERGOVIT; ALUTARD; ANTIALLERGIC AGENT; ANTIHISTAMINIC AGENT; BUDELIN NOVOLIZER; BUDESONIDE; CORTICOSTEROID; DEPIGOID; DESLORATADINE; GRASS POLLEN VACCINE; IMMUNOGLOBULIN E; IPRATROPIUM BROMIDE; OMALIZUMAB; PLACEBO; POLLINEX; STALORAL; UNCLASSIFIED DRUG;

ANAPHYLAXIS; ARTICLE; ASTHMA; BURNING SENSATION; CLINICAL EFFECTIVENESS; CLINICAL FEATURE; CLINICAL PRACTICE; COMPARATIVE EFFECTIVENESS; CONJUNCTIVITIS; COST BENEFIT ANALYSIS; COST CONTROL; COST EFFECTIVENESS ANALYSIS; COST UTILITY ANALYSIS; DIZZINESS; DOSAGE SCHEDULE COMPARISON; DOSE RESPONSE; DRUG DOSE INCREASE; DRUG HYPERSENSITIVITY; DRUG INDUCED HEADACHE; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; ECONOMIC EVALUATION; ERYTHEMA; EVIDENCE BASED MEDICINE; FATIGUE; FLUSHING; GASTROINTESTINAL SYMPTOM; HAY FEVER; HEALTH CARE COST; HUMAN; INJECTION SITE REACTION; MAINTENANCE THERAPY; MATHEMATICAL MODEL; META ANALYSIS; MOUTH DISEASE; MOUTH EDEMA; ORAL PRURITUS; OUTCOME ASSESSMENT; PRACTICE GUIDELINE; PRURITUS; QUALITY ADJUSTED LIFE YEAR; RESOURCE ALLOCATION; RHINITIS; SENSITIZATION; SIDE EFFECT; SKIN REDNESS; SUBCUTANEOUS IMMUNOTHERAPY; SUBLINGUAL IMMUNOTHERAPY; SWELLING; SYSTEMATIC REVIEW; THROAT IRRITATION; UNITED KINGDOM; UNSPECIFIED SIDE EFFECT; URTICARIA;

EID: 84880261820     PISSN: 13665278     EISSN: 20464924     Source Type: Journal    
DOI: 10.3310/hta17270     Document Type: Article

References (272)

1. 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;63:8. http://dx.doi.org/10.1111/j.1398-9995.2007.01620.x
2. Scadding GK, Durham SR, Mirakian R, Jones NS, Leech SC, Farooque S, et al. BSACI guidelines for the management of allergic and non-allergic rhinitis. Clin Exp Allergy 2008;38:19-42. http://dx.doi.org/10.1111/j.1365-2222.2007.02888.x
3. Bauchau V, Durham SR. Prevalence and rate of diagnosis of allergic rhinitis in Europe. Eur Respir J 2004;24:758-64. http://dx.doi.org/10.1183/09031936.04.00013904
4. Emberlin J. Hayfever prevalence in the UK in 2020, 2040 and 2060. Worcester: National Pollen and Aerobiology Research Unit, University of Worcester; 2009.
5. Asher MI, Montefort S, Bjorksten B, Lai CKW, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet 2006;368:733-43. http://dx.doi.org/10.1016/S0140-6736(06)69283-0
6. Bodtger U, Linneberg A. Remission of allergic rhinitis: an 8-year observational study. J Allergy Clin Immunol 2004;114:1384-8. http://dx.doi.org/10.1016/j.jaci.2004.08.039
7. Nihlén U, Greiff L, Montnémery P, Löfdahl CG, Johannisson A, Persson C, et al. Incidence and remission of self-reported allergic rhinitis symptoms in adults. Allergy 2006;61(11):1299-304.
8. Fiocchi A, Fox AT. Preventing progression of allergic rhinitis: the role of specific immunotherapy. Arch Dis Child Educ Pract 2011;96:91-100. http://dx.doi.org/10.1136/adc.2010.183095
9. Burgess JA, Haydn-Walters E, Byrnes GB, Matheson MC, Jenkins MA, Wharton CL, et al. Childhood allergic rhinitis predicts asthma incidence and persistence to middle-age: a longitudinal study. J Allergy Clin Immunol 2007;120:863-9. http://dx.doi.org/10.1016/j.jaci.2007.07.020
10. Gupta R, Sheikh A, Strachan DP, Anderson HR. Burden of allergic disease in the UK secondary analyses of national databases. Clin Exp Allergy 2004;34:520-6. http://dx.doi.org/10.1111/j.1365-2222.2004.1935.x
11. White P, Smith H, Baker N, Davis W, Frew A. Symptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy? Clin Exp Allergy 1998;28:266-70. http://dx.doi.org/10.1046/j.1365-2222.1998.00237.x
12. Focke M, Swoboda I, Marth K, Valenta R. Developments in allergen-specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen-specific immunoglobulin E and T cell reactivity. Clin Exp Allergy 2010;40:385-97. http://dx.doi.org/10.1111/j.1365-2222.2009.03443.x
13. Fitzhugh DJ, Lockey RF. History of immunotherapy: the first 100 years. Immunol Allergy Clin North Am 2011;31:149-57, vii. http://dx.doi.org/10.1016/j.iac.2011.03.003
14. Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. J Allergy Clin Immunol 2004;113:1025-34. http://dx.doi.org/10.1016/j.jaci.2004.03.024
15. Okuda M. [A long-term follow-up study after discontinuation of immunotherapy for Japanese cedar pollinosis.] Arerugi 2006;55:655-61.
16. Eng PA, Borer-Reinhold M, Heijnen IAFM, Gnehm HPE. Twelve-year follow-up after discontinuation of preseasonal grass pollen immunotherapy in childhood. Allergy 2006;61:198-201.http://dx.doi.org/10.1111/j.1398-9995.2006.01011.x
17. 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;341:468-75. http://dx.doi.org/10.1056/NEJM199908123410702
18. Durham SR, Emminger W, Kapp A, deMonchy JGR, Rak S, Scadding GK, et al. SQ-standardised sublingual grass immunotherapy: confirmation of disease modification 2 years after 3 years of treatment in a randomized trial. J Allergy Clin Immunol 2012;129:717-25.e5 [published online ahead of print 29 January 2012].
19. Walker SM, Durham SR, Till SJ, Roberts G, Corrigan CJ, Leech SC, et al. BSACI guidelines. Immunotherapy for allergic rhinitis. Clin Exp Allergy 2011;41:1177-200. http://dx.doi.org/10.1111/j.1365-2222.2011.03794.x
20. Committee on Safety of Medicines (CSM), Medicine Control Agency. Desensitising vaccines: new advice in current problems in pharmacovigilance. 1994. Report no. 20.
21. Cox L, Li JT, Nelson H, Lockey RF. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol 2007;120:S25-85. http://dx.doi.org/10.1016/j.jaci.2007.06.019
22. Cox L. Advantages and disadvantages of accelerated immunotherapy schedules. J Allergy Clin Immunol 2008;122:432-4. http://dx.doi.org/10.1016/j.jaci.2008.06.007
23. Alvarez-Cuesta E, Bousquet J, Canonica GW, Durham SR, Mailing HJ, Valovirta E. Standards for practical allergen-specific immunotherapy. Allergy 2006;61:1-20. http://dx.doi.org/10.1111/j.1398-9995.2006.01219_1.x
24. Didier A, Malling HJ, Worm M, Horak F, Jager S, Montagut A, et al. Optimal dose, efficacy, and safety of once-daily sublingual immunotherapy with a 5-grass pollen tablet for seasonal allergic rhinitis. J Allergy Clin Immunol 2007;120:1338-45. http://dx.doi.org/10.1016/j.jaci.2007.07.046
25. Didier A, Worm M, Horak F, Sussman G, de Beaumont O, Le Gall M, et al. Sustained 3-year efficacy for pre- and coseasonal 5-grass-pollen sublingual immunotherapy tablets in patients with grass pollen-induced rhinoconjunctivitis. J Allergy Clin Immunol 2011;128:559-66. http://dx.doi.org/10.1016/j.jaci.2011.06.022
26. Wahn U, Tabar A, Kuna P, Halken S, Montagut A, de Beaumont O, et al. Efficacy and safety of 5-grass-pollen sublingual immunotherapy tablets in pediatric allergic rhinoconjunctivitis. J Allergy Clin Immunol 2009;123:160-6. http://dx.doi.org/10.1016/j.jaci.2008.10.009
27. Sieber J, Koberlein J, Mosges R, Sieber J, Koberlein J, Mosges R. Sublingual immunotherapy in daily medical practice: effectiveness of different treatment schedules - IPD meta-analysis. Curr Med Res Opin 2010;26:925-32. http://dx.doi.org/10.1185/03007991003659483
28. More DR, Hagan LL. Factors affecting compliance with allergen immunotherapy at a military medical center. Ann Allergy Asthma Immunol 2002;88:391-4. http://dx.doi.org/10.1016/S1081-1206(10)62370-8
29. Cox L. Accelerated immunotherapy schedules: review of efficacy and safety. Ann Allergy Asthma Immunol 2006;97:126-37. http://dx.doi.org/10.1016/S1081-1206(10)60003-8
30. Chakraborty P, Roy I, Chatterjee S, Chanda S, Gupta-Bharracharya S. Phoenix sylvestris Roxb pollen allergy: a 2-year randomized controlled trial and follow-up study of immunotherapy in patients with seasonal allergy in an agricultural area of West Bengal, India. J Investig Allergol Clin Immunol 2006;16:377-84.
31. Ott H, Sieber J, Brehler R, Folster-Holst R, Kapp A, Klimek L, et al. Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study. Allergy 2009;64:1394-401. http://dx.doi.org/10.1111/j.1398-9995.2009.02194.x
32. Durham S, on behalf of the GT-08 investigators. Sustained effects of grass pollen AIT. Allergy 2011;66:50-2. http://dx.doi.org/10.1111/j.1398-9995.2011.02639.x
33. DesRoches 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;51:430-3. http://dx.doi.org/10.1111/j.1398-9995.1996.tb00155.x
34. DesRoches A, Paradis L, Menardo JL, Bouges S, Daures JP, 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;99:450-3. http://dx.doi.org/10.1016/S0091-6749(97)70069-1
35. Pajno GB, Vita D, Parmiani S, Caminiti L, La Grutta S, Barberio G. Impact of sublingual immunotherapy on seasonal asthma and skin reactivity in children allergic to Parietaria pollen treated with inhaled fluticasone propionate. Clin Exp Allergy 2003;33:1641-7. http://dx.doi.org/10.1111/j.1365-2222.2003.01809.x
36. Cox L, Esch RE, Corbett M, Hankin C, Nelson M, Plunkett G. Allergen immunotherapy practice in the United States: guidelines, measures, and outcomes. Ann Allergy Asthma Immunol 2011;107:289-99. http://dx.doi.org/10.1016/j.anai.2011.06.018
37. Cox L, Calderon MA. Subcutaneous specific immunotherapy for seasonal allergic rhinitis: a review of treatment practices in the US and Europe. Curr Med Res Opin 2010;26:2723-33. http://dx.doi.org/10.1185/03007995.2010.528647
38. Passalacqua G, Compalati E, Canonica GW. Advances in allergen-specific immunotherapy. Current Drug Targets 2009;10:1255-62. http://dx.doi.org/10.2174/138945009789753237
39. Committee for Medicinal Products for Human Use (CHMP). Guideline on allergen products: production and quality issues. London: EMA; 2008. Report no.: EMEA/CHMP/BWP/304831/2007.
40. Calderon MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, et al. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'. Allergy 2011;66:1345-59. http://dx.doi.org/10.1111/j.1398-9995.2011.02669.x
41. EAACI. Position paper: immunotherapy. Allergy 1993;48:9-35. http://dx.doi.org/10.1111/j.1398-9995.1993.tb04754.x
42. Gidaro GB, Marcucci F, Sensi L, Incorvaia C, Frati F, Ciprandi G. The safety of sublingual-swallow immunotherapy: an analysis of published studies. Clin Exp Allergy 2005;35:565-71. http://dx.doi.org/10.1111/j.1365-2222.2005.02240.x
43. Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol 1998;102:558-62. http://dx.doi.org/10.1016/S0091-6749(98)70271-4
44. Nelson HS. The use of standardized extracts in allergen immunotherapy. J Allergy Clin Immunol 2000;106:41-5. http://dx.doi.org/10.1067/mai.2000.107197
45. eMC (electronic Medicines Compendium). Summary of Product Characteristics (SPC). GRAZAX 75,000 SQ-T oral lyophilisate. URL: www.medicines.org.uk/EMC/medicine/19565/SPC/GRAZAX+75%2c000+SQ-T+oral+lyophilisate/ (accessed 10 May 2011).
46. British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. No. 63, March 2012. London: BMA and RPS; 2012.
47. Fell P, Brostoff J. A single dose desensitization for summer hay fever. Results of a double blind study-1988. Eur J Clin Pharmacol 1990;38:77-9. http://dx.doi.org/10.1007/BF00314808
48. Di Stanislao C, Di Berardino L, Bianchi I, Bologna G. A double-blind, placebo-controlled study of preventive immunotherapy with E.P.D, in the treatment of seasonal allergic disease. Allerg Immunol 1997;30:39-42.
49. Van Metre TE, Adkinson NF Jr, Amodio FJ, Lichtenstein LM, Mardiney MR, Norman PS, et al. A comparative study of the effectiveness of the Rinkel method and the current standard method of immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol 1980;66:500-13. http://dx.doi.org/10.1016/0091-6749(80)90012-3
50. Van Metre TEJ, Adkinson NF Jr, Lichtenstein LM, Mardiney MR Jr, Norman PS Jr, Rosenberg GL, et al. A controlled study of the effectiveness of the Rinkel method of immunotherapy for ragweed pollen hay fever. J Allergy Clin Immunol 1980;65:288-97. http://dx.doi.org/10.1016/0091-6749(80)90158-X
51. Casale TB, Stokes JR. Future forms of immunotherapy. J Allergy Clin Immunol 2011;127:8-15. http://dx.doi.org/10.1016/j.jaci.2010.10.034
52. Pauli G, Purohit A, Oster JP, de Blay F, Vrtala S, Niederberger V, et al. Comparison of genetically engineered hypoallergenic rBet v 1 derivatives with rBet v 1 wild-type by skin prick and intradermal testing: results obtained in a French population. Clin Exp Allergy 2000;30:1076-84. http://dx.doi.org/10.1046/j.1365-2222.2000.00869.x
53. Swoboda I, De Weerd N, Bhalla PL, Niederberger V, Sperr WR, Valent P, et al. Mutants of the major ryegrass pollen allergen, Lol p 5, with reduced IgE-binding capacity: candidates for grass pollen-specific immunotherapy. Eur J Immunol 2002;32:270-80. http://dx.doi.org/10.1002/1521-4141(200201)32:1270::AID-IMMU2703.0.CO;2-X
54. Jacobsen L, Niggemann B, Dreborg S, Ferdousi HA, Halken S, Host A, et al. Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study. Allergy 2007;62:943-8. http://dx.doi.org/10.1111/j.1398-9995.2007.01451.x
55. Möller C, Dreborg S, Ferdousi HA, Halken S, Høst A, Jacobsen L, et al. Pollen immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT study). J Allergy Clin Immunol 2002;109:251-6. http://dx.doi.org/10.1067/mai.2002.121317
56. Niggemann B, Jacobsen L, Dreborg S, Ferdousi HA, 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;61:855-9. http://dx.doi.org/10.1111/j.1398-9995.2006.01068.x
57. Novembre E, Galli E, Landi F, Caffarelli C, Pifferi M, De Marco E, et al. Coseasonal sublingual immunotherapy reduces the development of asthma in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 2004;114:851-7. http://dx.doi.org/10.1016/j.jaci.2004.07.012
58. Polosa R, Li Gotti F, Mangano G, Paolino G, Mastruzzo C, Vancheri C, et al. Effect of immunotherapy on asthma progression, BHR and sputum eosinophils in allergic rhinitis. Allergy 2004;59:1224-8. http://dx.doi.org/10.1111/j.1398-9995.2004.00537.x
59. ClinicalTrials.gov. Grazax asthma prevention (GAP). URL: http://clinicaltrials.gov/ct2/show/NCT01061203 (accessed 12 October 2011).
60. Brozek JL, Bousquet J, Baena-Cagnani CE, Bonini S, Canonica GW, Casale TB, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines: 2010 revision. J Allergy Clin Immunol 2010;126:466-76. http://dx.doi.org/10.1016/j.jaci.2010.06.047
61. British Thoracic Society and Scottish Intercollegiate Guidelines Network (SIGN). British guidelines on the management of asthma. A national clinical guideline. 2008. Report No.: 101.
62. Royal College of Physicians (RCP). Allergy services: still not meeting the unmet need. London: RCP; 2010.
63. Committee on Safety of Medicines. CSM Update. Desensitising vaccines. BMJ 1986;293:948. http://dx.doi.org/10.1136/bmj.293.6552.948
64. Committee for Medicinal Products for Human Use (CHMP). Guideline on the clinical development of products for specific immunotherapy for the treatment of allergic diseases. London: 2008. Report no.: CHMP/EWP/18504/2006.
65. Vance GH, Goldring S, Warner JO, Cox H, Sihra B, Hughes S, et al. A national audit of pollen immunotherapy for children in the United Kingdom: patient selection and programme safety. Clin Exp Allergy 2011;41:1313-23. http://dx.doi.org/10.1111/j.1365-2222.2011.03803.x
66. Allergy UK. Night and day. Every day report. A report based on research amongst people with allergic rhinitis. URL: www.allergyuk.org/download.aspx?File=leaflets/Night_and_Day_Report.pdf (accessed 8 June 2011).
67. British Society for Allergy and Clinical Immunology (BSACI). News release. Under performance during exams is linked to hay fever. URL: www.bsaci.org/index.php?option=com_content&task=view&id=184&Itemid=195 (accessed 11 May 2011).
68. Calderon MA, Alves B, Jacobson M, Hurwitz B, Sheikh A, Durham S. Allergen injection immunotherapy for seasonal allergic rhinitis. Cochrane Database Syst Rev 2007; Issue 1, Art No. CD001936. http://dx.doi.org/10.1002/14651858.CD001936.pub2
69. Karmakar PR, Das A, Chatterjee BP. Placebo-controlled immunotherapy with Cocos nucifera pollen extract. Int Arch Allergy Immunol 1994;103:194-201. http://dx.doi.org/10.1159/000236627
70. Bernstein DI, Epstein T. Systemic reactions to subcutaneous allergen immunotherapy. Immunol Allergy Clin North Am 2011;31:241-9. http://dx.doi.org/10.1016/j.iac.2011.02.007
71. Roder E, Berger MY, de GH, van-Wijk RG. Immunotherapy in children and adolescents with allergic rhinoconjunctivitis: a systematic review. Pediatr Allergy Immunol 2008;19:197-207. http://dx.doi.org/10.1111/j.1399-3038.2007.00648.x
72. Sanders S. The treatment of seasonal hay fever and asthma in children. A controlled trial of pre seasonal depot pollen therapy. Practitioner 1966;196:811-15.
73. Dreborg S, Agrell B, Foucard T, Kjellman NI, Koivikko A, Nilsson S. A double-blind, multicenter immunotherapy trial in children, using a purified and standardized Cladosporium herbarum preparation. Clinical results. Allergy 1986;41:131-40. http://dx.doi.org/10.1111/j.1398-9995.1986.tb00289.x
74. Fontana VJ, Holt LE Jr, Mainland D, Fontana VJ, Holt LEJ, Mainland D. Effectiveness of hyposensitization therapy in ragweed hay-fever in children. J Am Med Assoc 1966;195:985-92. http://dx.doi.org/10.1001/jama.1966.03100120053013
75. Weisnagel J. Nouvel agent hyposensibilisant dans le traitement de la rhinite allergique saisonnière (fièvre des foins) à l'herbe à poux chez l'enfant: le MRTA (modified ragweed tyrosine adsorbate). Union Med Canada 1979;108:685-90.
76. Wilson D, Torres Lima M, Durham SR. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2003;2:CD002893.
77. Di Bona D, Plaia A, Scafidi V, Leto-Barone MS, Di LG, Di Bona D, et al. Efficacy of sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: a systematic review and meta-analysis. J Allergy Clin Immunol 2010;126:558-66. http://dx.doi.org/10.1016/j.jaci.2010.06.013
78. Larenas-Linnemann D. Sublingual immunotherapy in children: complete and updated review supporting evidence of effect. Curr Opin Allergy Clin Immunol 2009;9:168-76. http://dx.doi.org/10.1097/ACI.0b013e328329a2a9
79. Olaguibel JM, varez Puebla MJ. Efficacy of sublingual allergen vaccination for respiratory allergy in children. Conclusions from one meta-analysis. J Investig Allergol Clin Immunol 2005;15:9-16.
80. Penagos M, Compalati E, Tarantini F, Baena-Cagnani R, Huerta J, Passalacqua G, et al. Efficacy of sublingual immunotherapy in the treatment of allergic rhinitis in pediatric patients 3 to 18 years of age: a meta-analysis of randomized, placebo-controlled, double-blind trials. Ann Allergy Asthma Immunol 2006;97:141-8. http://dx.doi.org/10.1016/S1081-1206(10)60004-X
81. Radulovic S, Calderon MA, Wilson DR, Durham SR. Cochrane systematic review: safety profile of sublingual immunotherapy (SLIT) for allergic rhinitis (AR). J Allergy Clin Immunol 2008;121:S142. http://dx.doi.org/10.1016/j.jaci.2007.12.1105
82. Sopo SM, Macchiaiolo M, Zorzi G, Tripodi S. Sublingual immunotherapy in asthma and rhinoconjunctivitis; systematic review of paediatric literature. Arch Dis Child 2004;89:620-4. http://dx.doi.org/10.1136/adc.2003.030411
83. Radulovic S, Calderon M, Wilson D, Durham S. Sublingual immunotherapy for allergic rhinitis. Cochrane Database Syst Rev 2010;12;CD002893. http://dx.doi.org/10.1002/14651858.CD002893.pub2
84. Bufe A, Ziegler-Kirbach E, Stoeckmann E, Heidemann P, Gehlhar K, Holland-Letz T, et al. Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study. Allergy 2004;59:498-504. http://dx.doi.org/10.1111/j.1398-9995.2004.00457.x
85. Bufe A, Eberle P, Franke-Beckmann E, Funck J, Kimmig M, Klimek L, et al. Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy. J Allergy Clin Immunol 2009;123:167-73. http://dx.doi.org/10.1016/j.jaci.2008.10.044
86. La Rosa M, Ranno C, Andre C, Carat F, Tosca MA, Canonica GW. Double-blind placebo-controlled evaluation of sublingual-swallow immunotherapy with standardized Parietaria judaica extract in children with allergic rhinoconjunctivitis. J Allergy Clin Immunol 1999;104:425-32. http://dx.doi.org/10.1016/S0091-6749(99)70388-X
87. Roder E, Berger MY, Hop WC, Bernsen RM, de Groot H, Gerth van WR. Sublingual immunotherapy with grass pollen is not effective in symptomatic youngsters in primary care. J Allergy Clin Immunol 2007;119:892-8. http://dx.doi.org/10.1016/j.jaci.2006.12.651
88. Rolinck-Werninghaus C, Wolf H, Liebke C, Baars JC, Lange J, Kopp MV, et al. A prospective, randomized, double-blind, placebo-controlled multi-centre study on the efficacy and safety of sublingual immunotherapy (SLIT) in children with seasonal allergic rhinoconjunctivitis to grass pollen. Allergy 2004;59:1285-93. http://dx.doi.org/10.1111/j.1398-9995.2004.00627.x
89. Vourdas D, Syrigou E, Carat F, Batard T, Andre C, Papageorgiou PS. Double-blind, placebo-controlled evaluation of sublingual immunotherapy with standardized olive pollen extract in pediatric patients with allergic rhinoconjunctivitis and mild asthma due to olive pollen sensitization. Allergy 1998;53:662-72. http://dx.doi.org/10.1111/j.1398-9995.1998.tb03952.x
90. Valovirta E, Jacobsen L, Ljorring C, Koivikko A, Savolainen J. Clinical efficacy and safety of sublingual immunotherapy with tree pollen extract in children. Allergy 2006;61:1177-83. http://dx.doi.org/10.1111/j.1398-9995.2006.01190.x
91. Drachenberg KJ, Wheeler AW, Stuebner P, Horak F. A well-tolerated grass pollen-specific allergy vaccine containing a novel adjuvant, monophosphoryl lipid A, reduced allergic symptoms after only four preseasonal injections. Allergy 2001;56:498-505. http://dx.doi.org/10.1034/j.1398-9995.2001.056006498.x
92. Caffarelli C, Sensi LG, Marcucci F, Cavagni G. Preseasonal local allergoid immunotherapy to grass pollen in children: a double-blind, placebo-controlled, randomized trial. Allergy 2000;55:1142-7. http://dx.doi.org/10.1034/j.1398-9995.2000.00655.x
93. Dahl R, Kapp A, Colombo G, deMonchy JGR, Rak S, Emminger W, et al. Efficacy and safety of sublingual immunotherapy with grass allergen tablets for seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;118:434-40. http://dx.doi.org/10.1016/j.jaci.2006.05.003
94. 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 multiallergen extract. J Allergy Clin Immunol 2009;124:150-6. http://dx.doi.org/10.1016/j.jaci.2009.04.037
95. Andre C, Perrin-Fayolle M, Grosclaude M, Couturier P, Basset D, Cornillon J, et al. A double-blind placebo-controlled evaluation of sublingual immunotherapy with standardized ragweed extract in patients with seasonal rhinitis. Int Arch Allergy Immunol 2003;131:111-18. http://dx.doi.org/10.1159/000070926
96. Ariano R, Spadolini I, Panzani RC. Efficacy of sublingual immunotherapy in Cupressaceae allergy using an extract of Cupressus arizonica. A double blind study. Allergol Immunopathol 2001;29:238-44.
97. Bowen T, Greenbaum J, Charbonneu Y, Hebert J, Filderman R, Sussman G, et al. Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjuctivitis. Annals Allergy Asthma Immunol 2004;93:425-30. http://dx.doi.org/10.1016/S1081-1206(10)61408-1
98. Casanovas M, Guerra F, Moreno C, Miguel R, Maranon F, Daza JC. Double-blind, placebo-controlled clinical trial of preseasonal treatment with allergenic extracts of Olea europaea pollen administered sublingually. J Invest Allergol Clin Immunol 1994;4:305-14.
99. D'Ambrosio F. Sublingual immunotherapy: a double-blind, placebo-controlled trial with Parietaria judaica extract standardised in mass units in patients with rhinoconjunctivitis, asthma, or both. Allergy 1999;54:968-73. http://dx.doi.org/10.1034/j.1398-9995.1999.00203.x
100. Dahl R, Stender A, Rak S. Specific immunotherapy with SQ standardized grass allergen tablets in asthmatics with rhinoconjunctivitis. Allergy 2006;61:185-90. http://dx.doi.org/10.1111/j.1398-9995.2005.00949.x
101. de Blay F, Purohit A, Kanny G, Le Sellin J, Wessel F, Leynadier F, et al. Sublingual-swallow immunotherapy with standardized 3-grass pollen extract: a double-blind placebo controlled study. Abstract. XXII Congress of the European Academy of Allergology and Clinical Immunology (EAACI), Paris, France, 7-11 June 2003, p. 780.
102. Di Rienzo V, Pucci S, D'Alo S, Di CG, Incorvaia C, Frati F, et al. Effects of high-dose sublingual immunotherapy on quality of life in patients with cypress-induced rhinitis: a placebo-controlled study. Clin Exp Allergy Rev 2006;6:67-70. http://dx.doi.org/10.1111/j.1365-2222.2005.00102.x
103. Dubakiene R, Kleinjans HAJ. Effectiveness of specific sublingual IT (SLIT) with tree pollen. A placebo controlled study in 119 patients. Abstract. XXII Congress of European Academy of Allergology and Clinical Immunology (EACCI), Paris, France, 7-11 June 2003.
104. Durham SR, Yang WH, Pedersen MR, Johansen N, Rak S. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:802-9. http://dx.doi.org/10.1016/j.jaci.2005.12.1358
105. Feliziani V, Lattuada G, Parmiani S, Dall'Aglio PP. Safety and efficacy of sublingual rush immunotherapy with grass allergen extracts. A double blind study. Allergol Immunopathol 1995;23:224-30.
106. Hordijk GJ, Antvelink JB, Luwema RA. Sublingual immunotherapy with a standardised grass pollen extract: a doubleblind, placebo-controlled study. Allergol Immunopathol 1998;26:234-40.
107. Lima M, Wilson DR, Roberts A, Walker SM, Durham SR. Grass pollen sublingual immunotherapy (SLIT) for seasonal rhinoconjunctivitis: a randomised controlled trial. Clin Exp Allergy 2002;32:507-14. http://dx.doi.org/10.1046/j.0954-7894.2002.01327.x
108. Ott H, Sieber J, Brehler R, Fölster-Holst R, Kapp A, Klimek L, et al. Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT study. Allergy 2009;64:179-86. [Erratum published in Allergy 2009;64:1394-401.] http://dx.doi.org/10.1111/j.1398-9995.2008.01875.x
109. Palma-Carlos AG, Santos AS, Branco-Ferreira M, Pregal AL, Palma-Carlos ML, Bruno ME, et al. Clinical efficacy and safety of preseasonal sublingual immunotherapy with grass pollen-carbamylated allergoid in rhinitis patients. A double-blind, placebo-controlled study. Allergol Immunopathol 2006;34:194-8. http://dx.doi.org/10.1157/13094026
110. Panzner P, Petrás M, Sýkora T, Lesná I. Double-blind, placebo controlled evaluation of grass pollen specific immunotherapy with oral drops administered sublingually or supralingually. Resp Medicine 2008;102:1296-304. http://dx.doi.org/10.1016/j.rmed.2008.03.024
111. Passalacqua G, Albano M, Riccio A, Fregonese L, Puccinelli P, Parmiani S, et al. Clinical and immunologic effects of a rush sublingual immunotherapy to Parietaria species: a double-blind, placebo-controlled trial. J Allergy Clinical Immunol 1999;104:964-8. http://dx.doi.org/10.1016/S0091-6749(99)70076-X
112. Peter R, Kleinjans H, Hecker H. Significant increase in IgG(4) levels after slit grass treatment. A double-blind, placebo-controlled, multi-center study (twin grasses study). Allergy 2009;90:353.
113. Pfaar O, Klimek L. Efficacy and safety of specific immunotherapy with a high-dose sublingual grass pollen preparation: a double blind, placebo-controlled trial. Ann Allergy Asthma Immunol 2008;100:256-63.
114. Pradalier A, Basset D, Claudel A, Couturier P, Wessel F, Galvain S, et al. Sublingual-swallow immunotherapy (SLIT) with a standardised five-grass-pollen extract (drops and sublingual tablets) versus placebo in seasonal rhinitis. Allergy 1999;54:819-28. http://dx.doi.org/10.1034/j.1398-9995.1999.00077.x
115. Smith H, White P, Annila I, Poole J, Andre C, Frew A. Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis. J Allergy Clin Immunol 2004;114:831-7. http://dx.doi.org/10.1016/j.jaci.2004.06.058
116. Troise C, Voltolini S, Canessa A, Pecora S, Negrini AC. Sublingual immunotherapy in Parietaria pollen-induced rhinitis: a double- blind study. J Invest Allergol Clin Immunol 1995;5:25-30.
117. Vervloet D, Birnbaum J, Laurent P, Hugues B, Fardeau MF, Massabie-Bouchat YP, et al. Safety and efficacy of Juniperus ashei sublingual-swallow ultra-rush pollen immunotherapy in cypress rhinoconjunctivitis: a double-blind, placebo-controlled study. Int Arch Allergy Immunol 2007;142:239-46. http://dx.doi.org/10.1159/000097026
118. Wessner DB, Wessner S, Mohrnschlager M, Rakoski J, Ring J. Efficacy and safety of sublingual immunotherapy in adults with allergic rhinoconjunctivitis: results after 2 years of controlled trial. Abstract. Allergy 2001;56(Suppl. 68):88.
119. Voltolini S, Modena P, Minale P, Bignardi D, Troise C, Puccinelli P, et al. Sublingual immunotherapy in tree pollen allergy. Double blind, placebo-controlled study with a biologically standardised extract of three pollens (alder, birch and hazel) administered by a rush schedule. Allergol Immunopathol 2001;29:103-10.
120. Valovirta E. PAT: the Preventive Allergy Treatment Study design and preliminary results. Wien Med Wochenschr 1999;149:442-3.
121. Wüthrich B, Bucher C, Jorg W, Bircher A, Eng P, Schneider Y, et al. Double-blind, placebo-controlled study with sublingual immunotherapy in children with seasonal allergic rhinitis to grass pollen. J Investig Allergol Clin Immunol 2003;13:145-8.
122. Yuksel H, Tanac R, Gousseinov A, Demir E. Sublingual immunotherapy and influence on urinary leukotrienes in seasonal pediatric allergy. J Investig Allergol Clin Immunol 1999;9:305-13.
123. Cox LS, Larenas LD, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol 2006;117:1021-35. http://dx.doi.org/10.1016/j.jaci.2006.02.040
124. Passalacqua G, Canonica GW. Sublingual immunotherapy for allergic respiratory diseases: efficacy and safety. Immunol Allergy Clin North Am 2011;31:265-77. http://dx.doi.org/10.1016/j.iac.2011.03.002
125. Pfaar O, Kleine-Tebbe J, Hormann K, Klimek L. Allergen-specific immunotherapy: which outcome measures are useful in monitoring clinical trials? Immunol Allergy Clin North Am 2011;31:289-309. http://dx.doi.org/10.1016/j.iac.2011.02.004
126. 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. http://dx.doi.org/10.1111/j.1398-9995.2009.02309.x
127. Hafner D, Reich K, Matricardi PM, Meyer H, Kettner J, Narkus A. Prospective validation of 'Allergy-Control-SCORE(TM)': a novel symptom-medication score for clinical trials. Allergy 2011;66:629-36. http://dx.doi.org/10.1111/j.1398-9995.2010.02531.x
128. Bousquet J, Schunemann HJ, Bousquet PJ, Bachert C, Canonica GW, Casale TB, et al. How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement. Allergy 2011;66:765-74. http://dx.doi.org/10.1111/j.1398-9995.2011.02590.x
129. Durham SR, Birk AO, Andersen JS. Days with severe symptoms: an additional efficacy endpoint in immunotherapy trials. Allergy 2011;66:120-3. http://dx.doi.org/10.1111/j.1398-9995.2010.02434.x
130. Ciprandi G, Klersy C, Cirillo I, Marseglia GL. Quality of life in allergic rhinitis: relationship with clinical, immunological, and functional aspects. Clin Exp Allergy 2007;37:1528-35.
131. Didier A, Melac M, Montagut A, Lheritier-Barrand M, Tabar A, Worm M. Agreement of efficacy assessments for five-grass pollen sublingual tablet immunotherapy. Allergy 2009;64:166-71. http://dx.doi.org/10.1111/j.1398-9995.2008.01767.x
132. Juniper EF, Guyatt GH. Development and testing of a new measure of health status for clinical trials in rhinoconjunctivitis. Clin Exp Allergy 1991;21:77-83. http://dx.doi.org/10.1111/j.1365-2222.1991.tb00807.x
133. Malling HJ. Immunotherapy as an effective tool in allergy treatment. Allergy 1998;53:461-72. http://dx.doi.org/10.1111/j.1398-9995.1998.tb04082.x
134. Canonica GW, Baena-Cagnani CE, Bousquet J, Bousquet PJ, Lockey RF, Malling HJ, et al. Recommendations for standardization of clinical trials with Allergen Specific Immunotherapy for respiratory allergy. A statement of a World Allergy Organization (WAO) taskforce. Allergy 2007;62:317-24. http://dx.doi.org/10.1111/j.1398-9995.2006.01312.x
135. Higgins JPT, Altman DG. Assessing risk of bias in included studies. In Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley-Blackwell; 2008. pp. 187-241. http://dx.doi.org/10.1002/9780470712184.ch8
136. Higgins JPT, Deeks JJ. Selecting studies and collecting data. In Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions. Chichester: Wiley-Blackwell; 2008. pp. 151-85. http://dx.doi.org/10.1002/9780470712184.ch7
137. Schunemann HJ, Oxman AD, Vist GE, Higgins JPT, Deeks JJ, Glasziou P, et al. Interpreting results and drawing conclusions. In Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley-Blackwell; 2008. pp. 359-87. http://dx.doi.org/10.1002/9780470712184.ch12
138. Donegan S, Williamson P, Gamble C, Tudur-Smith C. Indirect comparisons: a review of reporting and methodological quality. PLoS ONE 2010;5:e11054. http://dx.doi.org/10.1371/journal.pone.0011054
139. The BUGS project. URL: www.mrc-bsu.cam.ac.uk/bugs/winbugs/dicpage.shtml#q9 (accessed 29 February 2012).
140. Aberer W, von Weikersthal-Drachenberg F. European outcomes amongst allergic rhinoconjunctivitis patients participating in a placebo-controlled study of ultra short course subcutaneous immunotherapy (uSCIT) conducted during the 2007 grass pollen season. Allergy 2009;64:218.
141. Bhattacharya SG, Chakraborty P. A two-year aerobiological study and immunotherapy follow-up with Phoenix sylvestris pollen to seasonal allergic patients from West Bengal, India. J World Allergy Org 2007; November (XXth World Allergy Organization Congress & VIIth Asia Pacific Congress of Allergology, Asthma and Clinical Immunology, Bangkok, Thailand, 26 December 2007):S312.
142. Charpin D, Gouitaa M, Dron-Gonzalvez M, Fardeau MF, Massabie-Bouchat YP, Hugues B, et al. Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis: a double-blind, placebo-controlled study. Int Arch Allergy Immunol 2007;143:83-91. http://dx.doi.org/10.1159/000098656
143. Colas C, Monzon S, Venturini M, Lezaun A. Double-blind, placebo-controlled study with a modified therapeutic vaccine of Salsola kali (Russian thistle) administered through use of a cluster schedule. J Allergy Clin Immunol 2006;117:810-16. http://dx.doi.org/10.1016/j.jaci.2005.11.039
144. Creticos PS, Schroeder JT, Hamilton RG, Balcer-Whaley SL, Khattignavong AP, Lindblad R, et al. Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis. N Engl J Med 2006;355:1445-55. http://dx.doi.org/10.1056/NEJMoa052916
145. DuBuske LM, Frew AJ, Horak F, Keith PK, Corrigan CJ, Aberer W, et al. Ultrashort-specific immunotherapy successfully treats seasonal allergic rhinoconjunctivitis to grass pollen. Allergy Asthma Proc 2011;32:239-47. http://dx.doi.org/10.2500/aap.2011.32.3453
146. Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, et al. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol 2008;121:1120-5. http://dx.doi.org/10.1016/j.jaci.2008.01.072
147. Frew A, DuBuske L, Amersdorffer J, Holdich T. Significant benefits of combined symptom and medication scores for ultra short course subcutaneous immunotherapy compared with placebo in patients with grass pollen allergic rhinoconjunctivitis. Allergy 2009;64:227.
148. Hoiby AS, Strand V, Robinson DS, Sager A, Rak S, Hoiby AS, et al. Efficacy, safety, and immunological effects of a 2-year immunotherapy with Depigoid birch pollen extract: a randomized, double-blind, placebo-controlled study. Clin Exp Allergy 2010;40:1062-70. http://dx.doi.org/10.1111/j.1365-2222.2010.03521.x
149. Kettner J, Meyer H, Cromwell O, Narkus A, Jost K. Specific immunotherapy with recombinant birch pollen allergen rBet v 1-FV results of 2 years of treatment (Phase II trial). Allergy 2007;62:262.
150. Klimek L, Wolf H, Pfaar O, and Wustenberg E. Intraseasonal short-time updosing with SQ-standardised subcutaneous immunotherapy in patients with intermittent allergic rhinitis: a new therapeutic option. Allergy 2010;65:264.
151. Krishna T, Frew A, Durham S. Quality of life in specific immunotherapy with Alutard Sq grass pollen in allergic rhinoconjunctivitis: the Ukis-study results. J Allergy Clin Immunol 2006;117:S326. http://dx.doi.org/10.1016/j.jaci.2005.12.1288
152. Kuna P, Kaczmarek J, Kupczyk M. Efficacy and safety of immunotherapy for allergies to Alternaria alternata in children. J Allergy Clin Immunol 2011;127:502-8. http://dx.doi.org/10.1016/j.jaci.2010.11.036
153. Ljorring C, Shamji MH, Wnrtzen PA, Lund K, Frew AJ, Durham SR, et al. IgE-blocking antibodies may account for a large proportion of the observed treatment effect induced by specific immunotherapy (SIT). J Allergy Clin Immunol 2009;123:S154. http://dx.doi.org/10.1016/j.jaci.2008.12.577
154. Pauli G, Larsen TH, Rak S, Horak F, Pastorello E, Valenta R, et al. Efficacy of recombinant birch pollen vaccine for the treatment of birch-allergic rhinoconjunctivitis. J Allergy Clin Immunol 2008;122:951-60. http://dx.doi.org/10.1016/j.jaci.2008.09.017
155. Pfaar O, Robinson DS, Sager A, Emuzyte R. Immunotherapy with depigmented-polymerized mixed tree pollen extract: a clinical trial and responder analysis. Allergy 2010;65:1614-21. http://dx.doi.org/10.1111/j.1398-9995.2010.02413.x
156. Powell RJ, Frew AJ, Corrigan CJ, Durham SR. Effect of grass pollen immunotherapy with Alutard SQ((R)) on quality of life in seasonal allergic rhinoconjunctivitis. Allergy 2007;62:1335-8. http://dx.doi.org/10.1111/j.1398-9995.2007.01455.x
157. Sahin G, Pfaar O, Klimek L. Cluster-immunotherapy with a highly polymerized pollen extract: a randomized, double-blind, placebo-controlled study. Allergy 2011;66:652.
158. Ventura MT, Carretta A, Tummolo RA, Buquicchio R, Arsieni A, Murgia N. Clinical data and inflammation parameters in patients with cypress allergy treated with sublingual swallow therapy and subcutaneous immunotherapy. Int J Immunopathol Pharmacol 2009;22:403-13.
159. Casale TB, Busse WW, Kline JN, Ballas ZK, Moss MH, Townley RG, et al. Omalizumab pretreatment decreases acute reactions after rush immunotherapy for ragweed-induced seasonal allergic rhinitis. J Allergy Clin Immunol 2006;117:134-40. http://dx.doi.org/10.1016/j.jaci.2005.09.036
160. Ceuppens JL, Bullens D, Kleinjans H, van der Werf J. Immunotherapy with a modified birch pollen extract in allergic rhinoconjunctivitis: clinical and immunological effects. Clin Exp Allergy 2009;39:1903-9. http://dx.doi.org/10.1111/j.1365-2222.2009.03379.x
161. Frew AJ, Powell RJ, Corrigan CJ, Durham SR. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006;117:319-25. http://dx.doi.org/10.1016/j.jaci.2005.11.014
162. Meriney DK, Kothari H, Chinoy P, Grieco MH. The clinical and immunologic efficacy of immunotherapy with modified ragweed extract (allergoid) for ragweed hay fever. Ann Allergy 1986;56:34-8.
163. Balda BR, Wolf H, Baumgarten C, Klimek L, Rasp G, Kunkel G, et al. Tree-pollen allergy is efficiently treated by short-term immunotherapy (STI) with seven preseasonal injections of molecular standardized allergens. Allergy 1998;53:740-8. http://dx.doi.org/10.1111/j.1398-9995.1998.tb03969.x
164. Corrigan CJ, Kettner J, Doemer C, Cromwell O, Narkus A. Efficacy and safety of preseasonal-specific immunotherapy with an aluminium-adsorbed six-grass pollen allergoid. Allergy 2005;60:801-7. http://dx.doi.org/10.1111/j.1398-9995.2005.00790.x
165. Ferrer M, Burches E, Pelaez A, Munoz A, Hernandez D, Basomba A, et al. Double-blind, placebo-controlled study of immunotherapy with Parietaria judaica: clinical efficacy and tolerance. J Investig Allergol Clin Immunol 2005;15:283-92.
166. Jutel M, Jaeger L, Suck R, Meyer H, Fiebig H, Cromwell O. Allergen-specific immunotherapy with recombinant grass pollen allergens. J Allergy Clin Immunol 2005;116:608-13. http://dx.doi.org/10.1016/j.jaci.2005.06.004
167. Ortolani C, Pastorello EA, Incorvaia C, Ispano M, Farioli L, Zara C, et al. Double-blind, placebo-controlled study of immunotherapy with an alginate-conjugated extract of Parietaria judaica in patients with Parietaria hay-fever. Allergy 1994;49:13-21. http://dx.doi.org/10.1111/j.1398-9995.1994.tb00767.x
168. Zenner HP, Baumgarten C, Rasp G, Fuchs T, Kunkel G, Hauswald B, et al. Short-term immunotherapy: a prospective, randomized, double-blind, placebo-controlled multicenter study of molecular standardized grass and rye allergens in patients with grass pollen-induced allergic rhinitis. J Allergy Clin Immunol 1997;100:23-9. http://dx.doi.org/10.1016/S0091-6749(97)70190-8
169. Bodtger U, Poulsen LK, Jacobi HH, Malling HJ. The safety and efficacy of subcutaneous birch pollen immunotherapy: a one-year, randomised, double-blind, placebo-controlled study. Allergy 2002;57:297-305. http://dx.doi.org/10.1034/j.1398-9995.2002.1o3532.x
170. Bousquet J, Hejjaoui A, Soussana M, Michel FB. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. IV Comparison of the safety and efficacy of two dosages of a high-molecular-weight allergoid. J Allergy Clin Immunol 1990;85:490-7. http://dx.doi.org/10.1016/0091-6749(90)90160-6
171. Brewczynski PZ, Kroon AM. Efficacy and safety of immunotherapy with modified grass pollen allergens. Results of a placebo controlled study. [Wirksamkeit und vertraglichkeit einerimmuntherapie mit modifizierten graserpollenallergenen.] Allergologie 1999;22:411-20.
172. Varney VA, Gaga M, Frew AJ, Aber VR, Kay AB, Durham SR. Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs. BMJ 1991;302:265-9. http://dx.doi.org/10.1136/bmj.302.6771.265
173. Walker SM, Pajno GB, Torres-Lima M, Wilson DR, Durham SR. Grass pollen immunotherapy for seasonal rhinitis and asthma: a randomized, controlled trial. J Allergy Clin Immunol 2001;107:87-93. http://dx.doi.org/10.1067/mai.2001.112027
174. Ortolani C, Pastorello E, Moss RB, Hsu YP, Restuccia M, Joppolo G, et al. Grass pollen immunotherapy: a single year double-blind, placebo-controlled study in patients with grass pollen-induced asthma and rhinitis. J Allergy Clinical Immunol 1984;73:283-90. http://dx.doi.org/10.1016/S0091-6749(84)80021-4
175. Dolz I, Martinez-Cocera C, Bartolome JM, Cimarra M. A double blind, placebo-controlled study of immunotherapy with grass pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy. Allergy 1996;51:489-500.
176. Mirone C, Albert F, Tosi A, Mocchetti F, Mosca S, Giorgino M, et al. Efficacy and safety of subcutaneous immunotherapy with a biologically standardized extract of Ambrosia artemisiifolia pollen: a double-blind, placebo controlled study. Clin Exp Allergy 2004;34:1408-14. http://dx.doi.org/10.1111/j.1365-2222.2004.02056.x
177. Pastorello EA, Pravettoni V, Incorvaia C, Mambretti M, Franck E, Wahl R, et al. Clinical and immunological effects of immunotherapy with alum-absorbed grass allergoid in grass-pollen-induced hay-fever. Allergy 1992;47:281-90. http://dx.doi.org/10.1111/j.1398-9995.1992.tb02054.x
178. Bousquet J, Hejjaoui A, Skassa-Brociek W, Guerin B, Maasch HJ, Dhivert H, et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. I. Rush immunotherapy with allergoids and standardized orchard grass-pollen extract. J Allergy Clin Immunol 1987;80:591-8. http://dx.doi.org/10.1016/0091-6749(87)90013-3
179. Bousquet J, Maasch HJ, Hejjaoui A, Skassa-Brociek W, Wahl R, Dhivert H, et al. Double-blind, placebo-controlled immunotherapy with mixed grass-pollen allergoids. III. Efficacy and safety of unfractionated and high-molecular-weight preparations in rhinoconjunctivitis and asthma. J Allergy Clin Immunol 1989;84:546-56. http://dx.doi.org/10.1016/0091-6749(89)90369-2
180. Juniper EF, Roberts RS, Kennedy LK, O'Connor J, Syty-Golda M, Dolovich J, et al. Polyethylene glycol-modified ragweed pollen extract in rhinoconjunctivitis. J Allergy Clin Immunol 1985;75:578-85. http://dx.doi.org/10.1016/0091-6749(85)90033-8
181. Tari MG, Mancino M, Ghezzi E, Frank E, Cromwell O. Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study. Allergy 1997;52:65-74. http://dx.doi.org/10.1111/j.1398-9995.1997.tb02547.x
182. Fling JA, Ruff ME, Parker WA, Whisman BA, Martin ME, Moss RB, et al. Suppression of the late cutaneous response by immunotherapy. J Allergy Clin Immunol 1989;83:101-9. http://dx.doi.org/10.1016/0091-6749(89)90483-1
183. Metzger WJ, Clay DH, Richerson HB, Weiler JM, Donnelly A, Moran D. Clinical and immunologic evaluation of glutaraldehyde-modified, tyrosine-adsorbed short ragweed extract: A double-blind, placebo-controlled trial. J Allergy Clin Immunol 1981;68:442-8. http://dx.doi.org/10.1016/0091-6749(81)90198-6
184. Iliopoulos O, Proud D, Adkinson NJ, Creticos PS, Norman PS, Kagey S, et al. Effects of immunotherapy on the early, late, and rechallenge nasal reaction to provocation with allergen: changes in inflammatory mediators and cells. J Allergy Clin Immunol 1991;87:855-66. http://dx.doi.org/10.1016/0091-6749(91)90134-A
185. Bousquet J, Frank E, Soussana M, Hejjaoui A, Maasch HJ, Michel FB. Double-blind, placebo-controlled immunotherapy with a high-molecular-weight, formalinized allergoid in grass pollen allergy. Int Arch Allergy Appl Immunol 1987;82:550-2. http://dx.doi.org/10.1159/000234277
186. D'Amato G, Kordash TR, Liccardi G, Lobefalo G, Cazzola M, Freshwater LL. Immunotherapy with Alpare in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study. Clin Exp Allergy 1995; 25:149-58. http://dx.doi.org/10.1111/j.1365-2222.1995.tb01020.x
187. Grammer LC, Shaughnessy MA, Suszko IM, Shaughnessy JJ, Patterson R. A double-blind histamine placebo-controlled trial of polymerized whole grass for immunotherapy of grass allergy. J Allergy Clin Immunol 1983;72:448-53. http://dx.doi.org/10.1016/0091-6749(83)90580-8
188. Lee LK, Kniker WT, Campos T. Aggressive co-seasonal immunotherapy in mountain cedar pollen allergy. Arch Otolaryngol 1982;108:787-94. http://dx.doi.org/10.1001/archotol.1982.00790600031008
189. Blaiss M, Maloney J, Nolte H, Gawchik S, Yao R, Skoner DP. Efficacy and safety of timothy grass allergy immunotherapy tablets in North American children and adolescents. J Allergy Clin Immunol 2011;127:64-71. http://dx.doi.org/10.1016/j.jaci.2010.11.034
190. Cortellini G, Spadolini I, Patella V, Fabbri E, Santucci A, Severino M, et al. Sublingual immunotherapy for Alternaria-induced allergic rhinitis: a randomized placebo-controlled trial. Ann Allergy Asthma Immunol 2010;105:382-6. http://dx.doi.org/10.1016/j.anai.2010.08.007
191. Fujimura T, Yonekura S, Horiguchi S, Taniguchi Y, Saito A, Yasueda H, et al. Increase of regulatory T cells and the ratio of specific IgE to total IgE are candidates for response monitoring or prognostic biomarkers in 2-year sublingual immunotherapy (SLIT) for Japanese cedar pollinosis. Clin Immunol 2011;139:65-74. http://dx.doi.org/10.1016/j.clim.2010.12.022
192. Nelson HS, Nolte H, Creticos P, Maloney J, Wu J, Bernstein DI, et al. Efficacy and safety of timothy grass allergy immunotherapy tablet treatment in North American adults. J Allergy Clin Immunol 2011;127:72-80. http://dx.doi.org/10.1016/j.jaci.2010.11.035
193. Panizo C, Cimarra M, Gonzalez-Mancebo E, Vega A, Senent C, Martin S. In vivo and in vitro immunological changes induced by a short course of grass allergy immunotherapy tablets. J Investig Allergol Clin Immunol 2010;20:454-62.
194. Pfaar O, Barth C, Jaschke C, Hormann K, Klimek L. Sublingual allergen-specific immunotherapy adjuvanted with monophosphoryl lipid A: a phase I/IIa study. Int Arch Allergy Immunol 2011;154:336-44. http://dx.doi.org/10.1159/000321826
195. Reich K, Gessner C, Kroker A, Schwab JA, Pohl W, Villesen H, et al. Immunologic effects and tolerability profile of in-season initiation of a standardized-quality grass allergy immunotherapy tablet: a phase III, multicenter, randomized, double-blind, placebo-controlled trial in adults with grass pollen-induced rhinoconjunctivitis. Clinical Therapeutics 2011;33:828-40. http://dx.doi.org/10.1016/j.clinthera.2011.06.006
196. Skoner D, Gentile D, Bush R, Fasano MB, McLaughlin A, Esch RE, et al. Sublingual immunotherapy in patients with allergic rhinoconjunctivitis caused by ragweed pollen. Int Arch Allergy Immunol 2010;125:660-6.
197. Voltolini S, Troise C, Incorvaia C, Bignardi D, Di Cara G, Marcucci F, et al. Effectiveness of high dose sublingual immunotherapy to induce a stepdown of seasonal asthma: a pilot study. Curr Med Res Opin 2010;26:37-40. http://dx.doi.org/10.1185/03007990903431886
198. Blaiss M, Maloney J, Nolte H, Gawchik S, Skoner D. Efficacy and Safety of Grass Allergy Immunotherapy Tablet (AIT) in a North American Pediatric Population. Int Arch Allergy Immunol 2010;125:AB358.
199. Didier A, Horak F, Worm M, Melac M, de Beaumont O, Le Gall M. An assessment of sustained efficacy and safety of a 300 IR five-grass pollen sublingual immunotherapy tablet in adults with grass pollen induced allergic rhinoconjunctivitis during a 3-year treatment study. Allergy 2010;65:422.
200. Durham SR, Emminger W, Kapp A, Colombo G, de Monchy JGR, Rak S, et al. Long-term clinical efficacy in grass pollen-induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet. J Allergy Clin Immunol 2010;125:131-8. http://dx.doi.org/10.1016/j.jaci.2009.10.035
201. Dahl R, Kapp A, Ribel M, Durham SR. Sublingual immunotherapy with SQ standardized grass allergen tablets. Abstract. Annual Meeting of the AAAACI; 2006.
202. Horak F, Jaeger S, Worm M, Melac M, Didier A. Implementation of pre-seasonal sublingual immunotherapy with a five-grass pollen tablet during optimal dosage assessment. Clin Exp Allergy 2009;39:394-400. http://dx.doi.org/10.1111/j.1365-2222.2008.03153.x
203. Tari MG, Mancino M, Madonna F, Buzzoni L, Parmiani S. Immunologic evaluation of 24 month course of sublingual immunotherapy. Allergol Immunopathol 1994;22:209-16.
204. Bahceciler NN, Isik U, Barlan IB, Basaran MM. Efficacy of sublingual immunotherapy in children with asthma and rhinitis: a double blind, placebo-controlled study. Pediatr Pulmonol 2001;32:49-55. http://dx.doi.org/10.1002/ppul.1088
205. Cao LF, Lu Q, Gu HL, Chen YP, Zhang Y, Lu M, et al. Clinical evaluation for sublingual immunotherapy of allergic asthma and atopic rhinitis with Dermatophagoides farinae drops. Zhonghua Er Ke Za Zhi 2007;45:736-41.
206. Hirsch T, Sahn M, Leupold W. Double-blind placebo-controlled study of sublingual immunotherapy with house dust mite extract (D. pt.) in children. Pediatr Allergy Immunol 1997;8:21-7. http://dx.doi.org/10.1111/j.1399-3038.1997.tb00138.x
207. Marcucci F, Sensi L, Di Cara G, Salvatori S, Bernini M, Pecora S, et al. Three-year follow-up of clinical and inflammation parameters in children monosensitized to mites undergoing sub-lingual immunotherapy. Pediatr Allergy Immunol 2005;16:519-26. http://dx.doi.org/10.1111/j.1399-3038.2005.00301.x
208. Ibanez MD, Kaiser F, Knecht R, Armentia A, Schopfer H, Tholstrup B, et al. Safety of specific sublingual immunotherapy with SQ standardized grass allergen tablets in children. Pediatr Allergy Immunol 2007;18:516-22. http://dx.doi.org/10.1111/j.1399-3038.2007.00556.x
209. Calderon M, Essendrop M. Specific immunotherapy with high dose SQ standardized grass allergen tablets was safe and well tolerated. J Investig Allergol Clin Immunol 2006;16:338-44.
210. Khinchi MS, Poulsen LK, Carat F, Andre C, Hansen AB, Malling HJ. Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Allergy 2004;59:45-53. http://dx.doi.org/10.1046/j.1398-9995.2003.00387.x
211. Mauro M, Russello M, Incorvaia C, Gazzola GB, Di Cara G, Frati F. Comparison of efficacy, safety and immunologic effects of subcutaneous and sublingual immunotherapy in birch pollinosis: a randomized study. Eur Ann Allergy Clin Immunol 2007;39:119-22.
212. Quirino T, Iemoli E, Siciliani E, Parmiani S, Milazzo F. Sublingual versus injective immunotherapy in grass pollen allergic patients: a double blind (double dummy) study. Clin Exp Allergy 1996;26:1253-61. http://dx.doi.org/10.1111/j.1365-2222.1996.tb00522.x
213. Hróbjartsson A, Gøtzsche PC. Placebo interventions for all clinical conditions. Cochrane Database Syst Rev 2004;2:CD003974. http://dx.doi.org/10.1002/14651858.CD003974.pub2
214. Spiegelhalter SD, Abrams KR, Myles J. Baysian approaches to clinical trials and health care evaluation. Statistics in practice. Chichester: Wiley; 2004.
215. ClinicalTrials.gov website. Long-term effects of sublingual grass therapy. http://clinicaltrials.gov/show/NCT01335139 (accessed 21 November 2012).
216. ClinicalTrials.gov website. 2nd Pivotal Study rPhleum: adults and adolescents with rhinoconjunctivitis +/- controlled asthma. http://clinicaltrials.gov/ct2/show/NCT01353755?term=NCT01353755&rank=1 (accessed 21 November 2012).
217. ClinicalTrials.gov website. Evaluation of safety and efficacy of specific immunotherapy with recombinant major allergens of timothy grass pollen adsorbed onto aluminium-hydroxide in patients with IgE-mediated allergic rhinoconjunctivitis +/- controlled asthma (AMETHYST). http://clinicaltrials.gov/ct2/show/NCT00671268?term=NCT00671268&rank=1 (accessed 21 November 2012).
218. ClinicalTrials.gov website. Safety and efficacy of recombinant grass pollen allergen cocktail in the treatment of allergic rhinoconjunctivitis. http://clinicaltrials.gov/ct2/show/NCT00309036?term=NCT00309036&rank=1 (accessed 21 November 2012).
219. ClinicalTrials.gov website. Safety and efficacy of recombinant birch pollen allergen in the treatment of allergic rhinoconjunctivitis. http://clinicaltrials.gov/ct2/show/NCT00309062?term=NCT00309062&rank=1 (accessed 21 November 2012).
220. Philips Z, Ginnelly L, Sculpher M, Claxton K, Golder S, Riemsma R, et al. Review of guidelines for good practice in decision-analytic modelling in health technology assessment. Health Technol Assess 2004;8(36).
221. Evers S, Goossens M, de Vet H, van Tulder M, Ament A. Criteria list for assessment of methodological quality of economic evaluations: consensus on health economic criteria. Int J Technol Assess Health Care 2005;21:240-5.
222. 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;27:159-63.
223. Berto P, Bassu N, Incorvaia C, Frati F, Puccinelli P, Giaquinto C, et al. Cost effectiveness of sublingual immunotherapy in children with allergic rhinitis and asthma. Eur Ann Allergy Clin Immunol 2005;37:303-8.
224. Claes C, Mittendorf T, von der Schulenburg JM. Health economic modeling of allergen-specific immunotherapy in seasonal allergic rhinitis from a health care payer's perspective. Allergo J 2009;18:60-70.
225. Pokladnikova J, Krcmova I, Vlcek J. Economic evaluation of sublingual vs subcutaneous allergen immunotherapy. Brief record. Ann Allergy Asthma Immunol 2008;100:482-9. http://dx.doi.org/10.1016/S1081-1206(10)60475-9
226. Berto P, Passalacqua G, Crimi N, Frati F, Ortolani C, Senna G, et al. Economic evaluation of sublingual immunotherapy vs symptomatic treatment in adults with pollen-induced respiratory allergy: the Sublingual Immunotherapy Pollen Allergy Italy (SPAI) study. Structured abstract. Ann Allergy Asthma Immunol 2006;97:615-21. http://dx.doi.org/10.1016/S1081-1206(10)61090-3
227. Omnes LF, Bousquet J, Scheinmann P, Neukirch F, Jasso MG, Chicoye A, et al. Pharmacoeconomic assessment of specific immunotherapy versus current symptomatic treatment for allergic rhinitis and asthma in France. Structured abstract. Allergie Immunol 2007;39:148-56.
228. 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;37:772-9. http://dx.doi.org/10.1111/j.1365-2222.2007.02706.x
229. Brüggenjürgen B, Reubhold T, Brehler R, Laake E, Wiese G, Machate Uea. Cost-effectiveness of specific subcutaneous immunotherapy in patients with allergic rhinitis and allergic asthma. Ann Allergy Asthma Immunol 2008;101:316-24. http://dx.doi.org/10.1016/S1081-1206(10)60498-X
230. Canonica GW, Poulsen PB, Vestenbaek U. Cost-effectiveness of GRAZAX for prevention of grass pollen induced rhinoconjunctivitis in Southern Europe. Respir Med 2007;101:1885-94. http://dx.doi.org/10.1016/j.rmed.2007.05.003
231. Nasser S, Vestenbaek U, Beriot-Mathiot A, Poulsen PB. Cost-effectiveness of specific immunotherapy with Grazax in allergic rhinitis co-existing with asthma. Allergy 2008;63:1624-9. http://dx.doi.org/10.1111/j.1398-9995.2008.01743.x
232. Beriot-Mathiot A, Vestenbaek U, Poulsen PB. Influence of time horizon and treatment patterns on cost-effectiveness measures: the case of allergen-specific immunotherapy with Grazax. Provisional abstract. J Med Econ 2007;10:215-28. http://dx.doi.org/10.3111/13696990701438587
233. Keiding H, Jorgensen KP. A cost-effectiveness analysis of immunotherapy with SQ allergen extract for patients with seasonal allergic rhinoconjunctivitis in selected European countries. Curr Med Res Opin 2007;23:1113-20. http://dx.doi.org/10.1185/030079907X187865
234. Petersen KD, Gyrd HD, Dahl R. Health-economic analyses of subcutaneous specific immunotherapy for grass pollen and mite allergy. Allergol Immunopathol 2005;33:296-302. http://dx.doi.org/10.1016/S0301-0546(05)73246-8
235. Schadlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics 2000;17:37-52. http://dx.doi.org/10.2165/00019053-200017010-00003
236. Berto P, Frati F, Incorvaia C, Cadario G, Contiguglia R, Di GM, et al. Comparison of costs of sublingual immunotherapy and drug treatment in grass-pollen induced allergy: results from the SIMAP database study. Brief record. Curr Med Res Opin 2008;24:261-6. http://dx.doi.org/10.1185/030079908X253726
237. Hankin CS, Cox L, Bronstone A. The health economics of allergen immunotherapy. Immunol Allergy Clin North Am 2011;31:325-41. http://dx.doi.org/10.1016/j.iac.2011.03.007
238. Brecht JG, Schädlich PK. Krankheitslast chronischer Krankheiten in Deutschland. Hamburg: InForMed GmbH; 1995.
239. Büchner K. Die jährlichen Kosten der allergischen Rhinitis und des Asthmas in der Bundesrepublik Deutschland. Basel: Infratest-Suisse; 1993.
240. Wettengel R, Volmer T. Asthma: Medizinische und ökonomische Bedeutung einer Volkskrankheit. Stuttgart: EuMe-Com; 1994.
241. Andronis L, Barton P, Bryan S. Sensitivity analysis in economic evaluation: an audit of NICE current practice and a review of its use and value in decision-making. Health Technol Assess 2009;13(29).
242. Tamayama K, Kondo M, Shono A, Okubo I. Utility weights for allergic rhinitis based on a community survey with a time trade-off technique in Japan. Allergol Int 2009;58:201-7. http://dx.doi.org/10.2332/allergolint.08-OA-0032
243. Chen H, Cisternas MG, Katz PP, Omachi TA, Trupin L, Yelin EH, et al. Evaluating quality of life in patients with asthma and rhinitis: English adaptation of the rhinasthma questionnaire. Ann Allergy Asthma Immunol 2011;106:110-18. http://dx.doi.org/10.1016/j.anai.2010.10.027
244. Wasserfallen JB, Gold K, Schulman KA, Baraniuk JN. Item responsiveness of a rhinitis and asthma symptom score during a pollen season. J Asthma 1999;36:459-65. http://dx.doi.org/10.3109/02770909909087288
245. Whitehead S, Taylor MJ, Christensen J. An economic evaluation of Grazax for the treatment of grass pollen induced rhinoconjunctivitis in children. Value Health 2009;12:A125.
246. Whitehead SJ, Taylor MJ, Bech PG, Prenzler A. Cost-effectiveness of grazax in the paediatric population for the treatment of grass pollen induced rhinoconjunctivitis in Germany. Value Health 2009;12:A303.
247. Berto P, Frati F, Incorvaia C. Economic studies of immunotherapy: a review. Curr Opin Allergy Clin Immunol 2008;8:585-9. http://dx.doi.org/10.1097/ACI.0b013e32831411e9
248. Buchner K, Siepe M. Nutzen der Hyposensibilierung unter wirtschaftlichen Aspekten. Allergo J 1995;4:156-63.
249. National Institute for Clinical Excellence (NICE). Guide to the methods of technology appraisal. London: NICE; 2004.
250. British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. No. 62, September 2011. London: BMA and RPS; 2011.
251. Curtis L. Unit costs of health and social care 2011. URL: www.pssru.ac.uk/project-pages/unit-costs/2011/index.php (accessed 19 March 2012).
252. Medisave (UK) Ltd. Consumables and general supplies. URL: www.medisave.co.uk/consumables-general-supplies.html (accessed 17 March 2012).
253. Office for National Statistics (ONS) Annual survey of hours and earnings - 2011. URL: www.ons.gov.uk/ons/rel/ashe/annual-survey-of-hours-and-earnings/2011-provisional-results--soc-2010-/stb--ashe-results-2011--soc-2010-.html (accessed 19 March 2012).
254. Robinson S, Roberts T, Barton P, Bryan S, Macleod J, McCarthy A, et al. Healthcare and patient costs of a proactive chlamydia screening programme: the Chlamydia Screening Studies project. Sex Transm Infect 2007;83:276-81. http://dx.doi.org/10.1136/sti.2006.023374
255. Drummond MF, Sculpher MJ, O'Brien B, Stoddart GL, Torrance GW. Methods for the economic evaluation of health care programmes. Oxford: Oxford University Press; 2005.
256. Armitage P, Berry G, Matthews JNS. Statistical methods in medical research. 4th edn. Oxford: Blackwell Science; 2002. http://dx.doi.org/10.1002/9780470773666
257. Juniper EF, Roberts RS, Kennedy LK, O'Connor J, Syty Golda M, Dolovich J, et al. Polyethylene glycol-modifed ragweed; pollen extract in rhinoconjunctivitis. J Allergy Clin Immunol 1985;75:578-85. http://dx.doi.org/10.1016/0091-6749(85)90033-8
258. Cox L, Nelson H, Lockey R, Calabria C, Chacko T, Finegold I, et al. Allegeren immunotherapy: a practice parameter third update. J Allergy Clin Immunol 2011;127:S1-55. http://dx.doi.org/10.1016/j.jaci.2010.09.034
259. Sterne JAC, Egger M, Moher D, on behalf of the Cochrane Bias Methods Group. Addressing reporting biases. In Higgins JPT, Green S, editors. Cochrane handbook for systematic reviews of interventions. Chichester: Wiley-Blackwell; 2008. pp. 297-333. http://dx.doi.org/10.1002/9780470712184.ch10
260. The COMET Initiative. URL: www.comet-initiative.org/(accessed 28 February 2012).
261. Cox L, Larenas-Linnemann D, Lockey RF, Passalacqua G. Speaking the same language: the World Allergy Organization Subcutaneous Immunotherapy Systemic Reaction Grading System. J Allergy Clin Immunol 2010;125:569-74. http://dx.doi.org/10.1016/j.jaci.2009.10.060
262. Bousquet J, Bachert C, Canonica GW, Casale TB, Cruz AA, Lockey RJ, et al. Unmet needs in severe chronic upper airway disease (SCUAD). J Allergy Clin Immunol 2009;124:428-33. http://dx.doi.org/10.1016/j.jaci.2009.06.027
263. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F. Methods for meta-analysis in medical research. Chichester: Wiley; 2000.
264. Welton NJ, Caldwell DM, Adamopoulos E, Vedhara K. Mixed treatment comparison meta-analysis of complex interventions: psychological interventions in coronary heart disease. Am J Epidemiol 2009;169:1158-65. http://dx.doi.org/10.1093/aje/kwp014
265. Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J Roy Stat Soc A Sta 2009;172:137-59.
266. Gelman A. Prior distributions for variance parameters in hierarchical models. Bayesian Anal 2006;1:515-33. http://dx.doi.org/10.1214/06-BA117A
267. Racine-Poon A, Wakefield JC. Bayesian analysis of population pharmacokinetic and instantaneous pharmacodynamic relationships. In Berry DA, Stangl DK, editors. Bayesian biostatistics. New York, NY: Marcel Dekker; 1996. pp. 355-87.
268. Ntzoufras I. Bayesian modeling using WinBUGS. Hoboken, NJ: Wiley; 2009. http://dx.doi.org/10.1002/9780470434567
269. Spiegelhalter SD, Best NG, Carlin BP, van der Linde A. Bayesian measures of model complexity and fit. J Roy Stat Soc B Met 2002;64:583-639. http://dx.doi.org/10.1111/1467-9868.00353
270. Dahl R, Kapp A, Colombo G, de Monchy JGR, Rak S, Emminger W, et al. Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years. J Allergy Clin Immunol 2008;121:512-18. http://dx.doi.org/10.1016/j.jaci.2007.10.039
271. Schramm B, Ehlken B, Smala A, Quednau K, Berger K, Nowak D. Cost of illness of atopic asthma and seasonal allergic rhinitis in Germany: 1-yr retrospective study. Eur Respir J 2003;21:116-22.
272. Jacobsen L, Dreborg S, Moller C, Valovirta E, Wahn U, Urbanek R, et al. Preventive Allergy Treatment (PAT) by use of specific immunotherapy (SIT). Allergy 1995;50:50