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September 9, 2013

Role for SCIT


Because of the huge safety profile of SLIT versus SCIT, in terms of both recorded deaths and episodes of anaphylaxis, is there any role at all for SCIT in treating aeroallergen disease in countries where both are available and approved?


By Dr. Linda Cox

The answer to the question is: yes. There will be a role for SLIT and SCIT in the treatment of aeroallergen-induced allergic disease in countries where both are available.

Before explaining why I believe this is the case, I would like to address the first part of the question; the safety profile of SLIT versus SCIT. While I agree that SLIT has a more favorable safety profile than SCIT, which allows for home administration, I do not think there is a “huge” safety issue with SCIT when appropriately administered in a supervised medical setting. 1 To the contrary, most surveys and studies suggest the SCIT systemic rate is approximately 0.1 % of injections or 2 to 5 % of patients.2 In the AAAAI/ACAAI immunotherapy safety survey, there were no confirmed fatalities from 2008 to 2011, which included approximately 8 million injection visits per year. Previous AAAAI membership surveys reported SCIT-related fatalities at a rate of 1 in 2 to 2.5 million injections.3 The authors of the most recent AAAAI/ACAAI survey speculated that improved safety measures, especially regarding asthma assessment before SCIT injections, may be factor in the reduced SCIT mortality rate.4

In essence, I believe SCIT and SLIT have comparable safety when they are appropriately administered.

In terms of treatment efficacy, I think they are also reasonably comparable. However, there have been few well-controlled studies directly comparing the two methods. Two recent meta-analyses found that SCIT was more effective than SLIT in controlling rhinoconjuctivitis 5,6 and asthma symptoms.5

The magnitude of effect in many of the individual SCIT and SLIT studies appears to be similar and consistent with the WAO guideline recommendation of improved combined symptom-medication score of 20% greater than placebo.7,8

With comparable efficacy and safety profiles, when appropriately administered, factors that would clearly make one treatment preferred over the other – such that the other is longer used – are multiplex and include patient preference, costs, physician accessibility (geographic location, specialty training) and patients ability/willingness to comply with the treatment program. Both treatments have been found to be cost-effective. However, SLIT cost-efficacy has been demonstrated primarily in single allergen treatment studies.9 If a patient has more than one clinically relevant allergen sensitivity, the costs of SLIT related to allergen extracts may be prohibitive. In contrast, SCIT was associated with a significant cost savings (38% reduction) in a 12-year retrospective claims analysis study of a large US population (> 7 million adults & children), that compared health care cost and utilization of patients who received SCIT with a matched control population who did not.10 It can be presumed that the majority of patients in this study received multiallergen SCIT, as this is the common practice in the United States.11

The convenience of home-administered SLIT may clearly outweigh office-based SCIT in the beginning of treatment (updosing/build-up phase), but this “advantage” may be reversed during the maintenance phase. During this phase once a month office-visit injections may be preferred to daily tablets or drops.

Adherence with SCIT’s and SLIT’s multi-year treatment regimen has been shown equally problematic” ~16% adherence at year 3.12,13 Strategies aimed at monitoring and, if need be, improving adherence to both regimens are needed.

In summary, there is a role for SLIT and SCIT in the treatment of aeroallergen-induced disease. If appropriately administered, their efficacy and safety are comparable and factors such as patient preference (injection vs tablets/drops, monthly vs daily, etc.), patient profile (polysenisitized vs monosensitized, distant location vs near), and availability of the relevant allergen extracts will determine which treatment route is prescribed in locations where both are available.


  1. Cox L, Aaronson D, Casale T, Hansinger R, Weber R. Allergy Immunotherapy Safety: Location Matters! Journal of Allergy and Clinical Immunology: In Practice 2013;in press.
  2. 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, 74 e1-74 e7.
  3. Lockey RF, Benedict LM, Turkeltaub PC, Bukantz SC. Fatalities from immunotherapy (IT) and skin testing (ST). J Allergy Clin Immunol 1987;79:660-77.
  4. Epstein TG, Liss GM, Murphy-Berendts K, Bernstein DI. AAAAI and ACAAI surveillance study of subcutaneous immunotherapy, Year 3: what practices modify the risk of systemic reactions? Annals of Allergy, Asthma & Immunology 2013;110:274-8.e1.
  5. Chelladurai Y, Suarez-Cuervo C, Erekosima N, et al. Effectiveness of Subcutaneous Versus Sublingual Immunotherapy for the Treatment of Allergic Rhinoconjunctivitis and Asthma: A Systematic Review. Journal of Allergy and Clinical Immunology: In Practice 2013;1:361-9.
  6. Di Bona D, Plaia A, Leto-Barone MS, La Piana S, Di Lorenzo G. Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: A meta-analysis-based comparison. J Allergy Clin Immunol 2012;130:1097-107 e2.
  7. Frew A.J. PRJ, Corrigan C.J. , Durham S.R.,. Efficacy and safety of specific immunotherapy with SQ allergen extract in treatment-resistant seasonal allergic rhinoconjunctivitis J Allergy Clin Immunol 2006;117:319-25.
  8. Cox L, Casale T, Nayak A, et al. Efficacy And Safety Of Sublingual 300IR 5-grass Pollen Tablets In Adult Patients With Grass-pollen Rhinoconjunctivitis In United States. The Journal of Allergy and Clinical Immunology 2011;127:AB74.
  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;37:772-9.
  10. 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;131:1084-91.
  11. Esch RE. Specific immunotherapy in the U.S.A.: general concept and recent initiatives. Arb Paul Ehrlich Inst Bundesamt Sera Impfstoffe Frankf A M 2003:17-22; discussion 3.
  12. Senna G, Lombardi C, Canonica GW, Passalacqua G. How adherent to sublingual immunotherapy prescriptions are patients? The manufacturers' viewpoint. J Allergy Clin Immunol 2010;126:668-9.
  13. Hankin CS, Cox L, Lang D, et al. Allergy immunotherapy among Medicaid-enrolled children with allergic rhinitis: patterns of care, resource use, and costs. J Allergy Clin Immunol 2008;121:227-32.

Linda Cox, MD
Allergy and Asthma Center, Fort Lauderdale, Florida
Current President, American Academy of Allergy Asthma and Immunology
United States

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