***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Importance Epicutaneous immunotherapy may have potential for treating peanut allergy but has been assessed only in pre clinical and early human trials . Objective To determine the optimal dose , adverse events ( AEs ) , and efficacy of a peanut patch for peanut allergy treatment . Design , Setting , and Participants Phase 2b double-blind , placebo-controlled , dose-ranging trial of a peanut patch in peanut-allergic patients ( 6 - 55 years ) from 22 centers , with a 2-year , open-label extension ( July 31 , 2012-July 31 , 2014 ; extension completed September 29 , 2016 ) . Patients ( n = 221 ) had peanut sensitivity and positive double-blind , placebo-controlled food challenges to an eliciting dose of 300 mg or less of peanut protein . Interventions R and omly assigned patients ( 1:1:1:1 ) received an epicutaneous peanut patch containing 50 & mgr;g ( n = 53 ) , 100 & mgr;g ( n = 56 ) , or 250 & mgr;g ( n = 56 ) of peanut protein or a placebo patch ( n = 56 ) . Following daily patch application for 12 months , patients underwent a double-blind , placebo-controlled food challenge to establish changes in eliciting dose . Main Outcomes and Measures The primary efficacy end point was percentage of treatment responders ( eliciting dose : ≥10-times increase and /or reaching ≥1000 mg of peanut protein ) in each group vs placebo patch after 12 months . Secondary end points included percentage of responders by age strata and treatment-emergent adverse events ( TEAEs ) . Results Of 221 patients r and omized ( median age , 11 years [ quartile 1 , quartile 3 : 8 , 16 ] ; 37.6 % female ) , 93.7 % completed the trial . A significant absolute difference in response rates was observed at month 12 between the 250-&mgr;g ( n = 28 ; 50.0 % ) and placebo ( n = 14 ; 25.0 % ) patches ( difference , 25.0 % ; 95 % CI , 7.7%-42.3 % ; P = .01 ) . No significant difference was seen between the placebo patch vs the 100-&mgr;g patch . Because of statistical testing hierarchical rules , the 50-&mgr;g patch was not compared with placebo . Interaction by age group was only significant for the 250-&mgr;g patch ( P = .04 ) . In the 6- to 11-year stratum , the response rate difference between the 250-&mgr;g ( n = 15 ; 53.6 % ) and placebo ( n = 6 ; 19.4 % ) patches was 34.2 % ( 95 % CI , 11.1%-57.3 % ; P = .008 ) ; adolescents/adults showed no difference between the 250-&mgr;g ( n = 13 ; 46.4 % ) and placebo ( n = 8 ; 32.0 % ) patches : 14.4 % ( 95 % CI , −11.6 % to 40.4 % ; P = .40 ) . No dose-related serious AEs were observed . The percentage of patients with 1 or more TEAEs ( largely local skin reactions ) was similar across all groups in year 1 : 50-&mgr;g patch = 100 % , 100-&mgr;g patch = 98.2 % , 250-&mgr;g patch = 100 % , and placebo patch = 92.9 % . The overall median adherence was 97.6 % after 1 year ; the dropout rate for treatment-related AEs was 0.9 % . Conclusions and Relevance In this dose-ranging trial of peanut-allergic patients , the 250-&mgr;g peanut patch result ed in significant treatment response vs placebo patch following 12 months of therapy . These findings warrant a phase 3 trial . Trial Registration clinical trials.gov Identifier : Background : Peanut allergy is common , life‐threatening , and without therapeutic options . We evaluated peanut epicutaneous immunotherapy ( EPIT ) by using Viaskin Peanut for peanut allergy treatment . Objective : We sought to evaluate the clinical , safety , and immunologic effects of EPIT for the treatment of peanut allergy . Methods : In this multicenter , double‐blind , r and omized , placebo‐controlled study , 74 participants with peanut allergy ( ages 4‐25 years ) were treated with placebo ( n = 25 ) , Viaskin Peanut 100 & mgr;g ( VP100 ; n = 24 ) or Viaskin Peanut 250 & mgr;g ( VP250 ; n = 25 ; DBV Technologies , Montrouge , France ) . The primary outcome was treatment success after 52 weeks , which was defined as passing a 5044‐mg protein oral food challenge or achieving a 10‐fold or greater increase in successfully consumed dose from baseline to week 52 . Adverse reactions and mechanistic changes were assessed . Results : At week 52 , treatment success was achieved in 3 ( 12 % ) placebo‐treated participants , 11 ( 46 % ) VP100 participants , and 12 ( 48 % ) VP250 participants ( P = .005 and P = .003 , respectively , compared with placebo ; VP100 vs VP250 , P = .48 ) . Median change in successfully consumed doses were 0 , 43 , and 130 mg of protein in the placebo , VP100 , and VP250 groups , respectively ( placebo vs VP100 , P = .014 ; placebo vs VP250 , P = .003 ) . Treatment success was higher among younger children ( P = .03 ; age , 4‐11 vs > 11 years ) . Overall , 14.4 % of placebo doses and 79.8 % of VP100 and VP250 doses result ed in reactions , predominantly local patch‐site and mild reactions ( P = .003 ) . Increases in peanut‐specific IgG4 levels and IgG4/IgE ratios were observed in peanut EPIT‐treated participants , along with trends toward reduced basophil activation and peanut‐specific TH2 cytokines . Conclusions : Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks , with the highest responses among younger children . This , when coupled with a high adherence and retention rate and significant changes in immune pathways , supports further investigation of this novel therapy BACKGROUND Epicutaneous allergen administration using a patch may be an alternative to subcutaneous or sublingual immunotherapy . OBJECTIVE To optimize treatment dose and to demonstrate the efficacy and safety of epicutaneous immunotherapy . METHODS This monocentric , placebo-controlled , double-blind trial included 132 patients with grass pollen-induced rhinoconjunctivitis . In February 2008 , patients were r and omly allocated to receive placebo or 3 different doses of allergen . Before and during the pollen season 2008 , patients received 6 weekly patches . Efficacy was assessed 4 to 5 months later ( n = 110 ) and during the pollen season of the treatment-free follow-up year in 2009 ( n = 93 ) . The primary outcome was patient-reported changes in hay fever symptoms assessed by a visual analog scale . Secondary outcome measures were weekly visual analog scale symptom scores during pollen season , use of rescue medication , changes in conjunctival and skin reactivity , as well as safety . RESULTS Hay fever symptoms during the pollen season were reduced by more than 30 % in 2008 and by 24 % in 2009 in the high-dose group as compared with that in the placebo group , and the alleviation of symptoms in the follow-up year was dependent on the treatment dose . Higher allergen doses were associated with drug-related adverse events ( AEs ) , predominantly manifested by pruritus , erythema , wheal , or eczema . Eleven systemic AEs of grade s 1 to 2 required treatment and led to study exclusion . The dropout rate due to AEs was 8.3 % . No drug-related serious AE was recorded . CONCLUSION Epicutaneous immunotherapy is safe and efficacious in a dose-dependent manner after 6 patches only BACKGROUND Subcutaneous allergen-specific immunotherapy is an effective treatment of IgE-mediated allergies , but it requires repeated allergen injections with a risk of systemic allergic reactions . Transcutaneous immunotherapy may improve patient compliance and safety . OBJECTIVE To assess the safety and efficacy of epicutaneous allergen immunotherapy . METHODS This monocentric , placebo-controlled , double-blind trial was conducted from March 2006 to December 2007 at the University Hospital Zurich . Thirty-seven adult patients with positive skin prick and nasal provocation tests to grass pollen were r and omized  to receive patches containing either allergen ( n = 21 ) or placebo ( n = 16 ) . Treatment took place before and during the pollen season 2006 , and follow-up visits took place before ( n = 26 ) and after the pollen season 2007 ( n = 30 ) . The primary outcome measures were nasal provocation tests . RESULTS Allergen-treated patients showed significantly decreased scores in nasal provocation tests in the first ( P < .001 ) and second year ( P = .003 ) after treatment . In contrast , placebo-treated patients had decreased scores in the first treatment year , 2006 ( P = .03 ) , but the effect diminished in the second year ( P = .53 ) . Although improvement of nasal provocation test scores was not significantly better in the verum versus placebo group , the overall treatment success was rated significantly higher by the allergen-treated group than by the placebo group ( 2006 , P = .02 ; 2007 , P = .005 ) . No severe adverse events were observed . Occurrence of eczema after allergen patch applications proved stimulation of specific T-cell responses , but was noted as an adverse effect of the treatment . CONCLUSION Epicutaneous allergen immunotherapy is a promising strategy to treat allergies and merits further investigation Importance There are currently no approved treatments for peanut allergy . Objective To assess the efficacy and adverse events of epicutaneous immunotherapy with a peanut patch among peanut-allergic children . Design , Setting , and Participants Phase 3 , r and omized , double-blind , placebo-controlled trial conducted at 31 sites in 5 countries between January 8 , 2016 , and August 18 , 2017 . Participants included peanut-allergic children ( aged 4 - 11 years [ n = 356 ] without a history of a severe anaphylactic reaction ) developing objective symptoms during a double-blind , placebo-controlled food challenge at an eliciting dose of 300 mg or less of peanut protein . Interventions Daily treatment with peanut patch containing either 250 & mgr;g of peanut protein ( n = 238 ) or placebo ( n = 118 ) for 12 months . Main Outcomes and Measures The primary outcome was the percentage difference in responders between the peanut patch and placebo patch based on eliciting dose ( highest dose at which objective signs/symptoms of an immediate hypersensitivity reaction developed ) determined by food challenges at baseline and month 12 . Participants with baseline eliciting dose of 10 mg or less were responders if the posttreatment eliciting dose was 300 mg or more ; participants with baseline eliciting dose greater than 10 to 300 mg were responders if the posttreatment eliciting dose was 1000 mg or more . A threshold of 15 % or more on the lower bound of a 95 % CI around responder rate difference was prespecified to determine a positive trial result . Adverse event evaluation included collection of treatment-emergent adverse events ( TEAEs ) . Results Among 356 participants r and omized ( median age , 7 years ; 61.2 % male ) , 89.9 % completed the trial ; the mean treatment adherence was 98.5 % . The responder rate was 35.3 % with peanut-patch treatment vs 13.6 % with placebo ( difference , 21.7 % [ 95 % CI , 12.4%-29.8 % ; P < .001 ] ) . The prespecified lower bound of the CI threshold was not met . TEAEs , primarily patch application site reactions , occurred in 95.4 % and 89 % of active and placebo groups , respectively . The all-causes rate of discontinuation was 10.5 % in the peanut-patch group vs 9.3 % in the placebo group . Conclusions and Relevance Among peanut-allergic children aged 4 to 11 years , the percentage difference in responders at 12 months with the 250-&mgr;g peanut-patch therapy vs placebo was 21.7 % and was statistically significant , but did not meet the prespecified lower bound of the confidence interval criterion for a positive trial result . The clinical relevance of not meeting this lower bound of the 
    Output:
    
Conclusion : The systematic review suggests that EPIT might induce desensitization in peanut allergy and an increased risk of local AEs .