The Efficacy and Safety of Epicutaneous Immunotherapy for Allergic Diseases: A Systematic Review and Meta-Analysis

Abstract

<b><i>Objectives:</i></b> To systematically review the effect and safety of epicutaneous immunotherapy (EPIT) for allergic diseases. <b><i>Methods:</i></b> We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, CQ VIP Database, Wanfang Data, and international trial register from their inception to July 29, 2019, without language restrictions, for randomized controlled trials (RCTs) that compared EPIT versus no EPIT for allergen-triggered allergic reactions. We assessed certainty of evidence by the GRADE approach. <b><i>Results:</i></b> Ten RCTs with 1,085 participants (aged from 10 months to 65 years) comparing EPIT with placebo for peanut, cow milk, or grass-pollen allergy met the eligibility criteria. A substantial benefit in terms of desensitization in EPIT group was more likely for peanut or cow milk protein allergy (risk ratio [RR] 2.34, 95% CI 1.69–3.23; <i>I</i><sup>2</sup> = 0%; high certainty evidence). EPIT increased local-treatment-related adverse events (L-TRAE; RR 1.56, 95% CI 1.03–2.36; <i>I</i><sup>2</sup> = 82%; moderate certainty evidence). But there were no significantly increased risk of any TRAEs (low certainty evidence) or systemic-TRAEs (S-TRAEs; very low certainty evidence) in EPIT group. The incidence rate of serious AEs, the use of rescue medications, and anaphylactic reactions stratified by organ systems including skin and mucosa, eyes and upper respiratory, lower respiratory, and gastrointestinal system in EPIT group were similar to placebo group. In subgroup analysis, desensitization of EPIT was significantly effective in peanut allergy (RR 2.29, 95% CI 1.64–3.21; <i>I</i><sup>2</sup> = 0%) and children <12 years (RR 2.85, 95% CI 1.92–4.24; <i>I</i><sup>2</sup> = 0%) with high certainty evidence. Only epicutaneous grass-pollen immunotherapy significantly increased the risk of S-TRAE (RR 4.65, 95% CI 1.10–19.64; <i>I</i><sup>2</sup> = 0%). <b><i>Conclusion:</i></b> The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs. These findings should be interpreted with caution owing to the limited study and heterogeneity. More data in the older (children ≥12 years and adults) and other allergic diseases are needed.

Past, present, and future of allergen immunotherapy vaccines

“…91,92 An overview of experience gained in EPIT trials is summarized in a very recent review article. 93 This review concludes that "EPIT might induce desensitization in peanut allergy and an increased risk of local adverse events (AEs). These findings should be interpreted with caution owing to the limited study and heterogeneity.…”

“…More than 10 years ago the first studies appeared, suggesting epicutaneous allergen administration for epicutaneous immunotherapy (EPIT) 91,92 . An overview of experience gained in EPIT trials is summarized in a very recent review article 93 . This review concludes that “EPIT might induce desensitization in peanut allergy and an increased risk of local adverse events (AEs).…”

Novel vaccines for allergen-specific immunotherapy

“…Data from epicutaneous AIT (EPIT) studies performed with peanut allergen extracts provide evidence for clinical effects [ 37 ▪▪ , 38 ▪▪ ] (Table 1 ) but these effects are modest, and a systematic review and metaanalysis [ 39 ] concludes that more studies are necessary to understand if this form of AIT is effective. Furthermore, the mechanisms of EPIT are not clear as it has been demonstrated that epicutaneous allergen administration induces no relevant increases of allergen-specific IgG antibodies but rather increases allergen-specific T-cell activation [ 40 ].…”

From Allergen Molecules to Molecular Immunotherapy of Nut Allergy: A Hard Nut to Crack

“…Epicutaneous immunotherapy (EPIT) is a more recent approach which has been developed originally for AIT of respiratory allergy ( 288 ) but has now been evaluated also for AIT of peanut allergy ( 235 , 289 ). EPIT is based on the direct application of an allergen-containing patch on the patient´s skin, similar as it is performed in APT.…”

“…These findings should be interpreted with caution owing to the limited study and heterogeneity. More data in the older (children ≥ 12 years and adults) and other allergic diseases are needed” ( 289 ). The analysis of systemic peanut allergen-specific IgG responses has shown that epicutaneous allergen administration induces only a very modest production of allergen-specific IgG and mainly specific T cell activation ( 16 ).…”