Published Online: September 28, 2012
Allergen specific immunotherapy (ASI) is a unique therapy for allergic rhinitis because it modifies the allergic disease by targeting the underlying immunologic mechanisms. Sublingual (SLIT) and subcutaneous (SCIT) immunotherapy are the two most commonly prescribed routes for administering ASI, with considerable differences worldwide. In the United States SCIT is widely prescribed, since it is the only Food and Drug Administration (FDA) approved route, while SLIT is prescribed by only a small percentage of allergists (less than 6%); in contrast, in Europe SLIT is prescribed nearly as frequently as SCIT, and in southern Europe it accounts for approximately 80% of immunotherapy prescriptions. Several clinical trials demonstrated the efficacy of both SCIT and SLIT compared to placebo for seasonal allergic rhinitis to grass pollens, which is one of the most prevalent allergic diseases in the developed world. However, the relative efficacy of SCIT and SLIT has not yet been determined. The only two published comparative studies, one performed with grass allergens and another with birch pollen, were far too small to draw reliable conclusions.
In an article recently published in The Journal of Allergy & Clinical Immunology, Di Bona et al described an indirect approach to compare SLIT and SCIT for seasonal allergic rhinitis to grass pollens. The researchers indirectly compared randomized controlled trials (RCT) of SCIT and SLIT by meta-analysis of a fairly large number of double-blind, placebo-controlled trials on SCIT and SLIT (updating their previous published meta-analysis, published in JACI) in patients with seasonal allergic rhinitis to grass pollens. The evidence has to be considered indirect because it is based on trials comparing immunotherapy to placebo, not on a direct comparison between the two different treatments.
Description of Study
The authors identified 36 RCTs (22 for SLIT and 14 for SCIT) including a total of 3,014 patients treated with immunotherapy and 2,768 controls who received placebo. Symptom and medication scores were considered as measures of efficacy. SLIT was administered by sublingual drops in 10 RCTs and by tablets in 12 RCTs. Seven of the 22 SLIT studies enrolled only children (<18 years), another 2 included both adults and children; none of the 14 SCIT studies enrolled children only, although five of them included some patients under age 18. The sample size of the RCTs varied greatly (SLIT: 34-578 patients SCIT: 15- 943 patients). High variability was also observed in the dose of allergens administered both for SLIT and for SCIT. Withdrawals and drop-out rates varied among studies, (0-11% for SLIT, 0-21.2% for SCIT).
Results of Study
The authors found that SCIT was more effective than SLIT both in the reduction of symptoms (SCIT Symptom Score: SCIT, SMD, -0.92; 95%CI, -1.26 to -0.58; SLIT drops SMD, -0.25; 95%CI, -0.45 to -0.05; SLIT tablets SMD, -0.40; 95%CI, -0.54 to -0.27), and in the reduction of anti-allergic drug assumption (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). The evidence is strong for adults, while data from child studies are inconsistent (for SLIT) or missing (for SCIT). Secondary analyses showed that tablets are more effective than drops, in particular for reduction of symptoms, but this effect is likely due to the different dose administered, especially in child studies. Treatments lasting more than 1 year are more effective than short ultra-rush treatments for SCIT, while longer pre-seasonal treatments (>8 weeks) are associated with the higher response rate for SLIT.
The authors conclude that their results provide indirect but solid evidence that SCIT is more effective than SLIT in controlling symptoms and reducing the use of anti-allergic medications in seasonal allergic rhinoconjuntivitis to grass pollen.
The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.