Although all studies included in this analysis assessed the symptom score (SS) and medication score (MS) as outcome measures of the treatment effect, different scoring systems and scales were used. For this reason analyses were performed by the method of standardised mean differences (SMD), expressing the differences in means between SLIT and placebo. Effect sizes of 0.2, 0.5, and 0.8 corresponded to small, medium, and large effects, respectively. The SMDs reported for both SS and MS were around 0.2, corresponding to a small benefit of grass pollen allergy immunotherapy tablets in the treatment of seasonal allergic rhinoconjunctivitis.
Most studies enrolled patients with reported moderate or severe seasonal allergic rhinoconjunctivitis, corresponding to a mean SS without any treatment of 12.5 on an 18-point SS scale. To make the results easier to interpret, the authors analysed the 11 studies that used an 18-point SS scale – this showed SLIT was associated with a mean reduction on this scale of −0.83 (95% CI −1.03 to −0.63; P=0.001) versus placebo.
A large proportion of patients receiving SLIT experienced adverse events (70% v 44.5% with placebo), and the withdrawal rate for adverse events was higher (6.0% v 2.2%, respectively). Although no cases of anaphylaxis were reported, nine events in the SLIT group required epinephrine (7 treatment-related).
In their discussion, the study authors comment that the small clinical benefit noted may be due to several methodological defects in the analysis of the data. Other limitations discussed include participation of sponsor companies in study design and interpretation, lack of detail of randomisation or allocation concealment method in some studies, small sample sizes, and use of a per-protocol analysis in one study. They note however that their findings are consistent with previous investigations, and that the benefit of SLIT may be even lower than previously assessed due to the inclusion of more recent studies. They say that the continued widespread use of SLIT is questionable.
An editorial comment on this study states that “Sublingual immunotherapy may seem more convenient than nasal corticosteroids or subcutaneous immunotherapy and therefore tempting to prescribe, but the evidence shows minimal benefit and moderate adverse effects for patients with seasonal grass pollen allergies”.