Sublingual immunotherapy: efficacy--methodology and outcome of clinical trials.

Using Medline we identified 39 placebo-controlled, double-blind sublingual immunotherapy (SLIT) studies providing symptom-medication score. These were retrospectively evaluated for evidence of clinical efficacy and quality of study presentation. Clinical efficacy was estimated according to statistical significance and graded as: unequivocal efficacy (statistically significant difference from placebo in both symptom and medication scores or the combined score), which was observed in 28% of studies, possible efficacy (significant improvement in either symptom or medication scores) seen in 33%, and no efficacy (no statistical difference between active treatment and the placebo group), as found in 38% of studies. Generally, studies were limited by the number of patients, showed a high frequency of withdrawals, a short duration of treatment, and insufficient data on randomization. The magnitude of efficacy additional to placebo treatment must be >20% in order to justify the treatment. This review concludes that future SLIT studies should be planned in accordance with international recommendations in order to be conclusive.