Safety and Tolerability of Sublingual Immunotherapy in Clinical Trials and Real Life

Gianenrico Senna; Marco Caminati; Giorgio Walter Canonica


Curr Opin Allergy Clin Immunol. 2013;13(6):656-662. 

In This Article

Abstract and Introduction


Purpose of review Sublingual immunotherapy (SLIT) is effective in allergic rhinitis and asthma. Apart from its efficacy, safety is crucial as this treatment is usually self-administered at home. Tolerability also plays a pivotal role, as mild local reactions, although not life-threatening, may represent a risk for treatment withdrawal and can therefore negatively affect clinical outcomes. The present study addresses this issue by reviewing double-blind, placebo-controlled, randomized trials and real-life studies.

Recent findings The number of life-threatening SLIT-related reactions is negligible. SLIT-related adverse events are not always consistently reported nor uniformly classified in published studies. However, systemic reactions are rare and side effects mostly consist of mild, self-limiting local reactions. No treatment-related risk factors for adverse events have been clearly defined, as far as type of allergen, dose or schedule.

Summary SLIT provides an optimal safety profile both in children and in adults. Apart from life-threatening reactions, the lack of standardization of adverse events reporting may account for the wide variability of the prevalence of side effects in clinical trials and in real-life setting. It can lead to a possible underestimation of adverse events, concerning, in particular, local reactions. Since poor tolerability may affect adherence and cause treatment discontinuation, adopting shared strategies in order to recognize, grade and manage adverse events is mandatory.


Allergen-specific immunotherapy (SIT) has been used for over a century. It is the only causal treatment currently available for allergic respiratory disease. However, the risk of systemic side effects has been the main drawback of subcutaneous immunotherapy (SCIT) and has led to the development of new routes of allergen administration. More recently, nasal and oral immunotherapies had been proposed, but dismissed as possible options, firstly because nasal effects were bothersome, and secondly for lack of efficacy. Sublingual immunotherapy (SLIT) has been found to be effective in allergic rhinitis and asthma,[1,2] and its use is growing in Europe as well as in United States, even without US Food and Drug Administration (FDA) official approval.[3] Apart from its efficacy, safety of SLIT is a crucial parameter as this treatment is usually self-administered at home. In this study, we address this issue by reviewing the double-blind, placebo-controlled, randomized clinical trials (DB-PC-RCTs), as well as postmarketing surveillances published up to now. Moreover, we also investigate the tolerability of SLIT, as mild reactions, although local and not life-threatening, may represent a risk for treatment withdrawal and therefore can negatively affect clinical outcomes.