ALLERGEN IMMUNOTHERAPY: EFFICACY, PERSISTENCE, CONSISTENCY, AND COST EFFECTIVENESS

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Abstract

Although allergen immunotherapy (AIT) has been used for the treatment of allergic rhinitis (AR), allergic conjunctivitis, asthma, stinging insect hypersensitivity, and atopic dermatitis for over 100 years, it has been slow to gain universal acceptance. With the publication of the “World Health Organization Position Paper, Allergen Immunotherapy” in 1998 which summarized the scientific evidence for the efficacy and long-term benefit of this therapy, it has become an accepted and respected modality of treatment. In this review there are discussed following topics of allergen immunotherapy: the reasons for recommending AIT, mechanism of action, subcutaneous and sublingual methods of application, duration, adherence and cost effectiveness. It is necessary to support, not blame, the patient for nonadherence as it is the responsibility of the patient, the physician, and the health-care system to create an environment in which the patient can be adherent. Nonadherence is multifactorial in most every patient and the physician must address all of the factors if adherence is to be improved. The greatest challenge is taking the time to create an individualized patient-tailored strategy to improve adherence, as one size does not fit all. Adherence is dynamic and selecting the best time to start AIT and assuring that there is close follow-up through AIT years of treatment is essential. The patient who is persistent and consistent in year one of AIT may not continue to be so in year three without added encouragement and support. The health-care systems and professional organizations need to help train physicians and their staff both in efficient and accurate ways to assess nonadherence and in implementing interventions to optimize adherence. The multidisciplinary approach to treating this disease of nonadherence will require the involvement of all healthcare professionals, researchers, professional organizations, insurance companies, and policy-makers.

About the authors

Dana Wallace

Nova Southeastern University School of Medicine, Fort Lauderdale, Florida, USA

Email: drdanawallace@gmail.com

References

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
  26. Franklin W, Lowell FC. Comparison of two dosages of ragweed extract in the treatment of pollenosis. JAMA. 1967;201[12]:915-7.
  27. Johnstone DE, Dutton A. The value of hyposensitization therapy for bronchial asthma in children - a 14-year study. Pediatrics. 1968;42[5]:793-802.
  28. 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.
  29. 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.
  30. Durham SR, investigators GT. Sustained effects of grass pollen AIT. Allergy. 2011;66 Suppl 95:50-2.
  31. 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.
  32. 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.
  33. Frati F, Dell'Albani I, Incorvaia C. Long-term efficacy of allergen immunotherapy: what do we expect? Immunotherapy. 2013;5[2]:131-3.
  34. 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.
  35. 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.
  36. 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.
  37. Cox L, Cohn JR. Duration of allergen immunotherapy in respiratory allergy: when is enough, enough? Ann Allergy Asthma Immunol. 2007;98[5]:416-26.
  38. Brehler R, Klimek L, Kopp MV, Christian Virchow J. Specific immunotherapy-indications and mode of action. Dtsch Arztebl Int. 2013;110[9]:148-58.
  39. 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.
  40. 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.
  41. 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.
  42. 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.
  43. 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.
  44. 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.
  45. 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.
  46. 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.
  47. 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.
  48. 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.
  49. Sabate E. Adherence to Long-Term Therapies: Evidence for Action. Geneva, Switzerland; 2003.
  50. 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.
  51. 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.
  52. 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.
  53. 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.
  54. 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.
  55. 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.
  56. 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.
  57. 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.
  58. Lamkin M, Elliott C. Curing the disobedient patient: medication adherence programs as pharmaceutical marketing tools. J Law Med Ethics. 2014;42[4]:492-500.
  59. 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.
  60. Rhodes BJ. Patient dropouts before completion of optimal dose, multiple allergen immunotherapy. Ann Allergy Asthma Immunol. 1999;82[3]:281-6.
  61. 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.
  62. 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.
  63. 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.
  64. Vita D, Caminiti L, Ruggeri P, Pajno GB. Sublingual immunotherapy: adherence based on timing and monitoring control visits. Allergy. 2010;65[5]:668-9.
  65. 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.
  66. 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.
  67. 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.
  68. 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.
  69. 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.
  70. 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.
  71. More DR, Hagan LL. Factors affecting compliance with allergen immunotherapy at a military medical center. Ann Allergy Asthma Immunol. 2002;88[4]:391-4.
  72. 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.
  73. 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.
  74. 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.
  75. 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.
  76. Jonasson G, Carlsen KH, Mowinckel P. Asthma drug adherence in a long term clinical trial. Arch Dis Child. 2000;83[4]:330-3.
  77. 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.
  78. May JR, Dolen WK. Management of Allergic Rhinitis: A Review for the Community Pharmacist. Clin Ther. 2017;39[12]:2410-9.
  79. 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.
  80. 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.
  81. DiMatteo MR. Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med Care. 2004;42[3]:200-9.
  82. Bender BG. Can health care organizations improve health behavior and treatment adherence? Popul Health Manag. 2014;17[2]:71-8.
  83. 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.
  84. 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.
  85. Lockey RF, Hankin CS. Health economics of allergen-specific immunotherapy in the United States. J Allergy Clin Immunol. 2011;127[1]:39-43.
  86. 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.
  87. Hankin CS, Cox L. Allergy immunotherapy: what is the evidence for cost saving? Curr Opin Allergy Clin Immunol. 2014;14[4]:363-70.
  88. Canonica GW, Passalacqua G. Disease-modifying effect and economic implications of sublingual immunotherapy. J Allergy Clin Immunol. 2011;127[1]:44-5.
  89. 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.
  90. 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.
  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.
  92. 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.
  93. 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.
  94. Pokladnikova J, Krcmova I, Vlcek J. Economic evaluation of sublingual vs subcutaneous allergen immunotherapy. Ann Allergy Asthma Immunol. 2008;100[5]:482-9.
  95. 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.
  96. Schadlich PK, Brecht JG. Economic evaluation of specific immunotherapy versus symptomatic treatment of allergic rhinitis in Germany. Pharmacoeconomics. 2000;17[1]: 37-52.

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