I was approached about the use of grass tablets to use for sublingual immunotherapy (projecting in the fall). While this isn't "news", I was surprised at the claims made about comparisons between monotherapy with grass and our current poly-allergen treatment with subQ route. Am I correct that some but not all studies show equal efficacy between the oral tablets and subQ injections? I was also under the impression that comparison between single grass pollen tablets and our current subQ multiple allergen mixes have not been performed--could you enlighten me on this as well. Thank you.


Thank you for your inquiry.

I believe the best way for me to answer your question is to direct you to what I feel is probably the best, to date, review of the issue of subcutaneous versus sublingual immunotherapy (Di Bona, et al). I have copied below several sections of this article for your convenience. These sections adequately summarize the results of the authors metaanalysis comparing these two forms of therapy.

I believe that the thoughts expressed in this article adequately reflect my own opinion, at this time, regarding these two treatments. I have also copied below abstracts of other publications should you wish to obtain a more through perspective regarding the comparative efficacy of the two therapies.

Thank you again for your inquiry and we hope this response is helpful to you.

Immunotherapy. 2011 Jun;3(6):747-56. doi: 10.2217/imt.11.48.
Subcutaneous versus sublingual immunotherapy for allergic rhinitis and/or asthma.
Bahceciler NN, Cobanoglu N.
Pediatric Pulmonology, Faculty of Medicine, Near East University, Nicosia, Cyprus. Abstract
Subcutaneous allergen-specific immunotherapy has long been used in allergic rhinitis and/or asthma and has been recognized to be efficacious. However, owing to the inconvenience of injection and the risk of serious side effects, alternative concepts inspiring the search for effective noninjective routes, namely sublingual administration of allergens, have emerged. Sublingual immunotherapy (SLIT) appears to be associated with a lower incidence of systemic reactions. The clinical efficacy of subcutaneous immunotherapy (SCIT) is well established for both rhinitis and asthma. Meta-analyses relating to its efficacy on asthma and rhinitis are available. SLIT has also been validated in this respect. Comparative clinical studies of SLIT versus SCIT are scarce demonstrating both routes to be clinically efficient. Knowledge of the exact mechanism of action of SLIT has been increasing in the last decade. In addition, recent studies have proved similarities of the immunological changes with the treatment of both routes. Further comparative clinical and immunological studies of SLIT versus SCIT are needed to confirm the long-term efficacy and to complete the knowledge of immunological mechanisms of both routes. Moreover, better understanding of the interaction of allergen and oral mucosal dendritic cells during SLIT may allow improved targeting of SLIT vaccines.

Am J Rhinol Allergy. 2012 Jan-Feb;26(1):18-22. doi: 10.2500/ajra.2012.26.3691.
Subcutaneous and sublingual immunotherapy for allergic rhinitis: what is the evidence?
Wise SK, Schlosser RJ.
Department of Otolaryngology-Head and Neck Surgery, Emory University, Atlanta, Georgia, USA.
Background: Increasing interest in sublingual immunotherapy (SLIT) among practitioners and patients has resulted in numerous publications and clinical trials in recent years. With the clinical growth of SLIT, discussions of its efficacy, safety, and immunologic effects have intensified, as have comparisons to subcutaneous immunotherapy (SCIT). In the United States, SCIT has been the traditional form of immunotherapy for inhalant allergy and is the only immunotherapy method approved by the U.S. Food and Drug Administration at this time. The similarities and differences between SLIT and SCIT are often discussed, yet clinical studies directly comparing these immunotherapy methods are scarce.
Methods: A literature review of specific issues and controversies between SLIT and SCIT for allergic rhinitis was conducted.
Results: Safety, efficacy, and immunologic effects of these two immunotherapy techniques are reviewed.
Conclusion: Unanswered questions relating to SLIT are examined.

Efficacy of subcutaneous and sublingual immunotherapy with grass allergens for seasonal allergic rhinitis: A meta-analysis¨Cbased comparison
Di Bona et al:The Journal of Allergy and Clinical Immunology
Volume 130, Issue 5 , Pages 1097-1107.e2, November 2012
Background: Subcutaneous (SCIT) and sublingual (SLIT) immunotherapy are the 2 most prescribed routes for administering allergen-specific immunotherapy. They were shown to be effective in control of symptoms and in reducing rescue medication use in patients with allergic diseases, but their effectiveness has to be balanced against side effects. In recent years, SLIT has been increasingly prescribed, instead of SCIT, because of improved safety and easy administration.
Objective: We assessed which route is the most effective in the treatment of patients with seasonal allergic rhinitis to grass pollen.
Methods: An indirect meta-analysis¨Cbased comparison between SCIT and SLIT was performed. Treatment efficacy was determined as the standardized mean difference (SMD) in symptom and medication scores obtained with active treatment, SCIT or SLIT, compared with placebo. Studies were included if they were double-blind randomized controlled trials comparing SCIT or SLIT with placebo. Thirty-six randomized controlled trials (3014 patients; 2768 controls) were analyzed.
Results: The overall effect size of SCIT for symptom score (SMD, −0.92; 95%CI, −1.26 to −0.58) was significantly higher than SLIT, both administered via drops (SMD, −0.25; 95% CI, −0.45 to −0.05) and tablets (SMD, −0.40; 95%CI, −0.54 to −0.27). Similar results were reported for medication score (SCIT: SMD, −0.58; 95% CI, −0.86 to −0.30. SLIT drops: SMD, −0.37; 95% CI, −0.74 to −0.00. SLIT tablets SMD, −0.30; 95% CI, −0.44 to −0.16).
Conclusions: Our results provide indirect but solid evidence that SCIT is more effective than SLIT in controlling symptoms and in reducing the use of antiallergic medications in seasonal allergic rhinoconjuntivitis to grass pollen.

In conclusion, the available data provide indirect evidence that for seasonal allergic rhinoconjunctivitis SCIT with grass allergens is more effective than SLIT in the control of symptoms and in the reduction of antiallergic medications. Trials directly comparing these 2 routes of immunotherapy are needed to confirm this evidence.

On the basis of the findings from this and the previous meta-analysis,6 an ideal comparative study should be a randomized, placebo-controlled, double-blind, double-dummy study that enrolls a large number of patients from a single center or a single country or a few countries with similar pollen exposure and with people of similar ethnicity. The treatment should be started at least 16 weeks before the expected beginning of the pollen season and should last 1 or 2 years. A vaccine with a dose of the main extract ¡Ý275 ¦Ìg for SLIT should be used. The ideal dose for SCIT vaccines has still to be defined.

Phil Lieberman, M.D.

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