Subcutaneous Versus Sublingual Immunotherapy for Allergic Rhinitis and/or Asthma

Nerin Nadir Bahceciler; Nazan Cobanoglu


Immunotherapy. 2011;3(6):747-756. 

In This Article

Clinical Efficacy

Subcutaneous Immunotherapy

Allergic rhinitis is certainly the disease in which SCIT efficacy is the most documented and proved. A meta-analysis was published in 2007 in the frame of the Cochrane collaboration.[20] A total of 51 trials including a total of 2871 participants were considered. None of them was conducted exclusively in children, but participants younger than 18 years of age were included in nine studies. Allergens tested were ragweed (n = 12), mixed grass (n = 16), Timothy (n = 5), Parietaria (n = 6), birch (n = 4), orchard (n = 2), cedar (n = 3), Bermuda (n = 1), Juniperus ashei (n = 1) and cocos (n = 1). A total of 15 studies suitable for symptom score analysis demonstrated a significant reduction. The medication score analysis (13 studies) showed a significant reduction in the specific immunotherapy group. It is worth noting that there was a significant heterogeneity among these studies. Passalacqua and colleagues updated this work in the frame of the GALEN network by collecting 15 recent studies published between 2000 and 2006.[21] Reduction of symptoms and/or the need for medications were confirmed with grass, birch, Parietaria and ragweed pollens, and HDMs. In addition, SCIT-treated patients' quality of life significantly improved.[22–24]

The proof of SIT efficiency in asthma has long been served by a meta-analysis by Abramson and colleagues, first published in 1995,[25] and then kept regularly up to date in the frame of the Cochrane Institute.[26–28] The allergens used in the trials were dust mite, pollen, animal dander, Cladosporium, latex and multiple allergens.

The latest Cochrane meta-analysis including 88 trials demonstrated a significant improvement in asthma symptom scores (standardized mean difference: -0.59; 95% CI: -0.83 to -0.35) and it would have been necessary to treat three patients (95% CI: 3–5) with immunotherapy to avoid one deterioration in asthma symptoms. Overall, it would have been necessary to treat four patients (95% CI: 3–6) with immunotherapy to avoid one requiring increased medication. This meta-analysis also showed significant reduction in specific bronchial hyper-reactivity.[29]

Sublingual Immunotherapy

To date, sublingual immunotherapy (SLIT) has been tested in rhinitis and asthma in approximately 40 double-blind, placebo-controlled (DBPC) studies. Indeed, four meta-analyses were published in the frame of the Cochrane collaboration[12] or with the Cochrane collaboration method.[30–32]

The first meta-analysis of SLIT for allergic rhinitis included 22 trials up to September 2002 and 979 patients. It concluded that SLIT was significantly more effective than placebo,[33] but the studies in allergic asthma were too few to perform a meta-analysis. A meta-analysis in asthma was recently repeated, including 25 trials (either open or blinded) and involving more than 1000 adults and children.[34] This meta-analysis demonstrated a significant effect of SLIT for most of the considered outcomes (symptoms plus medications, pulmonary function and overall improvement), with the exception of asthma symptoms alone. Another meta-analysis[30] of SLIT for allergic rhinitis in pediatric patients (aged 4–18 years) involved ten trials and 484 subjects demonstrating that SLIT was significantly more effective than placebo, as assessed by the reduction in both symptom scores and rescue medication usage. Although all the studies were of high methodological quality, there was a relevant heterogeneity (I2 >80%) owing to the large variability in study design, duration, outcome measures and inclusion criteria. Finally, a meta-analysis was also performed for asthma in pediatric patients.[31] This article included nine DBPC trials and 441 patients, and found a significant effect of SLIT on both asthma symptoms and rescue medication usage. Also in this case, the heterogeneity of the trials was very large (I2 >90%). The meta-analyses mentioned pooled together all the allergens, whereas a systematic evaluation of the efficacy of one specific allergen is available only for HDM[35] with positive results. In addition, it is noteworthy that in some pollen studies, positive results were delayed to the second year of treatment[36,37] and studies using a mix of various pollen extracts are negative[38] or marginally positive.[39]

The studies previously reported were mainly conducted with sublingual drops of extracts. Recently, sublingual orodispersible allergen tablets were developed in grass pollen immunotherapy, and are expected to rapidly replace the liquid formulation. During the last 3 years, adequately powered, well-designed, DBPC randomized controlled trials involving several hundreds of patients with allergic rhinitis and/or asthma using standardized grass pollen tablets were published.[40–46] In those studies, the magnitude of the effect, defined as the reduction in diary symptom and rescue medication scores compared with placebo was reported as 16 and 28%,[40] 30 and 38%,[46] 35 and 46%,[41] 28 and 24%,[43] 24 and 34%,[45] respectively.

Only few studies were specifically designed to assess the effect of SLIT tablets in asthma,[42,47–52] and most of them confirmed a significant effect on symptoms and/or medication intake. In the three asthma studies that reported negative results,[42,50,51] the patients were almost completely free of asthma symptoms at enrollment and remained so during the trial, so that the absence of efficacy is not substantiated. Only two DBPC randomized controlled trials assessed the efficacy of multiple noncross-reacting allergens.[53,54] The first one used grass and olive extracts, and confirmed the efficacy of SLIT in rhinitis. The second one compared the efficacy of SLIT with grass alone or with grass plus nine other pollens and found that the treatment with a single allergen had more effect on immunological parameters than that with multiple allergens. Owing to the low pollen count, no clinical difference between the two groups and placebo was observed in this study.


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