MP 2.01.17

Sublingual Immunotherapy as a Technique of Allergen Specific Therapy

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Medical Policy
Section Medicine	Original Policy Date 3/31/96	Last Review Status/Date Reviewed with literature search/2:2009
Issue 2:2009		Return to Medical Policy Index

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Disclaimer

Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract.  Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage.  Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

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Description

Policy

Policy Guidelines

No applicable information

Benefit Application

Rationale

This policy is based on a 2003 TEC Assessment of sublingual immunotherapy (SLIT) that offered the following observations and conclusions (1):

2005 Update

A search of the literature was performed for the period of 2003 through February 2005. No additional published articles were identified that would prompt reconsideration of the policy statement, which remains unchanged. A number of randomized placebo-controlled trials were identified, (2-4) however, as noted in the 2003 TEC Assessment, the relevant comparison group is the gold standard of injection ASIT. One controlled trial comparing SLIT with injection ASIT in 75 patients was identified. (5) This trial randomized patients to 1 of 3 groups, SLIT, ASIT, or placebo. Thus there were only 25 patients in each group. There was no significant difference in the outcomes in either group. Therefore, the limitations noted in the TEC Assessment remain and the policy statement is unchanged.

2006 Update

A literature search was performed for the period of February 2005 through August 2006. The results of that review do not change the policy statement. Trials continue to be reported comparing sublingual immunotherapy (SLIT) with no treatment; for example, Durham and colleagues reported positive findings using grass allergen tablets for seasonal rhinoconjunctivitis. (6) However, trials have not been reported that compare SLIT with the standard subcutaneous injection immunotherapy. As noted above, these comparisons are needed to adequately evaluate SLIT. A recent review also commented that there is no allergy extract approved for this use (by the U.S. Food and Drug Administration) in the United States. (7)

2007 - 2008 Update
A literature search was performed for the period August 2006 through February 2008. Although additional studies were published, the policy statement is unchanged because no allergy extracts have been approved by the FDA for this use.
Nineteen non-US (17 European, 2 Asian) randomized placebo-controlled studies were identified, 8 of them in children. These studies report SLIT use for grass pollen, birch pollen, house dust mites, cat dander and latex allergens in allergic rhinoconjunctivitis, atopic dermatitis and asthma over a median of 9 months (range, 10 days to 3 years). Two meta-analyses related to asthma were published, one in children (8) and another in children and adults (9). A significant effect (using standardized mean difference) for symptoms (n=441) and medication use (n=366) was found in the analyses of SLIT use in children with asthma, although effect on medication use was driven by 2 studies. (8) Asthma parameters (n=876) showed small but significant improvements (using standardized mean difference) in the Cochrane meta-analysis of adults and children with asthma as well (9), although when just symptoms were analyzed (n=303), there was a non-significant improvement using SLIT over placebo. Only one direct comparison to allergen-specific immunotherapy (ASIT) was identified. (10) This was a one-month, randomized, non-blinded trial of SLIT vs. ASIT in 47 patients with birch allergy in which 34 patients (72%) completed the trial. No differences were noted in symptom and medication scores. Immunoglobulin levels were varied: not significantly different for IgE and significantly increased for IgG4 for ASIT but not SLIT. Despite extensive study, questions with SLIT remain. These include optimal dosing, duration of treatment, and the use of multiple allergens; and ideally comparison to ASIT and placebo.
In conclusion, given the lack of FDA approval and lack of adequate outcome data, this is considered investigational.

2009 Update
No products have been specifically approved by the FDA for use in sublingual immunotherapy as of January 2009; thus the policy statement is unchanged.

References:

1. 2003 TEC Assessment: Sublingual Immunotherapy for Allergies.
2. Bowen T, Greenbaum J, Charbonneau Y et al.Canadian trial of sublingual swallow immunotherapy for ragweed rhinoconjunctivitis. Ann Allergy Asthma Immunol 2004; 93(5):425-30.
3. Smith H, White P, Annila I et al. Randomized controlled trial of high-dose sublingual immunotherapy to treat seasonal allergic rhinitis. J Allergy Clin Immunol 2004; 114(4):831-7.
4. Bufe A, Ziegler-Kirbach E, Stoeckmann E et al. Efficacy of sublingual swallow immunotherapy in children with severe grass pollen allergic symptoms: a double-blind placebo-controlled study. Allergy 2004; 59(5):498-504.
5. Khinchi MS, Poulsen LK, Carat F et al.Clinical efficacy of sublingual and subcutaneous birch pollen allergen-specific immunotherapy: a randomized, placebo-controlled, double-blind, double-dummy study. Allergy 2004; 59(1):45-53.
6. Durham SR, Yang WH, Pedersen MR et al. Sublingual immunotherapy with once-daily grass allergen tablets: a randomized controlled trial in seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 2006; 117(4):802-9.
7. Cox LS, Linnemann DL, Nolte H et al. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol 2006; 117(5):1021-35.
8. Penagos M, Passalacqua G, Compalati E et al. Metaanalysis of the efficacy of sublingual immunotherapy in the treatment of allergic asthma in pediatric patients, 3 to 18 years of age. Chest 2008; 133(3): 599-609.
9. Calamita Z, Saconato H, Pelá AB et al. Efficacy of sublingual immunotherapy in asthma: systematic review of randomized-clinical trials using the Cochrane Collaboration method. Allergy 2006; 61(10):1162-72.
10. Mauro M, Russello M, Incorvaia C et al. 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(4):119-22.

Index

Policy History

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