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Wise et al.

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medication, and that SLIT results in an efficacy on top of the symptom improvement obtained with rescue medication.

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Efficacy in children.: Over 5 years ago, Dutch colleagues analyzed systematic reviews of SLIT in children and concluded that the methodological quality should be improved. They especially questioned the heterogeneity of the included trials and the risk of bias. 1669 Roder et al. 1670 also determined in 2008 that there was not enough evidence to support the usefulness of SLIT in children. These flaws have been improved in recent studies. There is strong 1671 evidence that grass pollen SLIT tablets in children reduce symptoms of AR. The evidence for aqueous SLIT is moderate. 1672 The evidence for HDM SLIT is of moderate-to low quality. Efficacy of SLIT over pharmacotherapy.: For PAR, SLIT with HDM tablets is more effective than any single pharmacotherapy, including antihistamines, antileukotrienes and INCS. 1673 For SAR, grass and ragweed tablet SLIT is almost as effective as INCS and more effective than the other pharmacotherapies. 1673 These data had already been confirmed for the SLIT grass pollen tablets by a previous meta-analysis; in this publication the separate analysis of the 5-grass tablet showed its superiority over all pharmacotherapy treatments. 1332 Efficacy of SLIT compared to SCIT.: Several investigators have tried to compare the efficacy of SLIT against that of SCIT. Most meta-analyses are based on indirect comparisons, as there are only a very few direct head-to-head randomized trials comparing both treatments; therefore, the evidence that SCIT is more effective than SLIT is weak. Also in children, SCIT seems more effective than SLIT, but again the quality of evidence is low. 1672 Safety.: Rare systemic and serious adverse events have been reported with SLIT, but in general, meta-analyses found SLIT to be safer than SCIT. In the complete data-set of systemic reviews there were 7 reports of the use of epinephrine in the SLIT group and 1 case of eosinophilic esophagitis with a grass pollen SLIT tablet. There was no administration of epinephrine in trials outside of the United States. A 2012 review by Calderon et al. 1674 estimated the anaphylaxis rate of SLIT to be 1 per 100 million doses, or 1 per 526,000 treatment years. Grass pollen SLIT tablets are just as safe in AR patients with and without mild asthma. 1675 Starting SLIT in-season appeared to be safe. Although there were 2 serious treatment-related adverse events with co-seasonal SLIT initiation, none required epinephrine administration. 1676 In the United States, the FDA requires patients be prescribed an epinephrine autoinjector and the first dose be given in the physician’s office for those on SLIT tablets. Continuing AIT during pregnancy did not augment the incidence of adverse outcomes during delivery nor alter the risk of developing atopic disease in the offspring. No conclusion can be drawn regarding the safety of starting SLIT in a pregnant woman, due to lack of cases. 1677 Preventative effects.: There are no systematic reviews specifically addressing the preventative effects of SLIT that fall within the allowable search date range of this ICAR:AR document. The preventative effect SLIT on asthma development was investigated in an open RCT by Marogna et al. 1678 involving 216 children treated with SLIT for 3 years. Mild

Int Forum Allergy Rhinol . Author manuscript; available in PMC 2020 June 10.