***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: BACKGROUND Sublingual immunotherapy with liquid extracts provides an appealing alternative to subcutaneous immunotherapy for the treatment of allergic rhinoconjunctivitis ( ARC ) , but a lack of robust evidence has deterred its use in North America . OBJECTIVE To determine the efficacy and tolerability of st and ardized glycerinated short ragweed sublingual allergen immunotherapy liquid ( RW-SAIL ) extract in subjects with ragweed-related ARC . METHODS This phase 3 , r and omized , placebo-controlled trial was conducted in North America . Subjects ( age range , 18 - 55 years ) with or without asthma were selected based on ARC symptom severity and erythema skin prick reaction to short ragweed . Subjects self-administered the maximum tolerated dose of RW-SAIL ( n = 218 ) or placebo ( n = 211 ) daily beginning approximately 8 to 16 weeks before and through the end of the ragweed pollen season . The primary end point was subject-assessed total combined daily rhinoconjunctivitis symptom and medication scores ( TCS ) . RESULTS During the entire season , there was a 43 % decrease in TCS in subjects treated with RW-SAIL compared with placebo . Similar decreases were observed in TCS between the 2 groups during peak season ( 42 % ) and in daily symptom scores during the entire ( 42 % ) and peak ( 41 % ) seasons . The occurrence of adverse events was similar between the treatment groups ; most were mild in severity . Treatment-related oromucosal local application site reactions occurred early and were transient and self-limited . No anaphylaxis occurred . CONCLUSIONS This is the first successful North American confirmatory phase 3 clinical trial to demonstrate the safety and efficacy of a sublingual st and ardized ragweed allergen immunotherapy liquid extract for the treatment of ARC BACKGROUND The efficacy and safety of the 300-index of reactivity ( IR ) dose of 5-grass-pollen sublingual immunotherapy ( SLIT ) tablets ( Stallergènes , Antony , France ) have been demonstrated for the treatment of hay fever in adults . OBJECTIVE We sought to assess the efficacy and safety of this tablet in children and adolescents with grass pollen-related allergic rhinitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 278 children ( 5 - 17 years of age ) with grass pollen-related rhinoconjunctivitis ( confirmed by means of a positive grass pollen skin prick test response and serum-specific IgE measurement ) received once-daily SLIT tablets or placebo . Treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was the rhinoconjunctivitis total symptom score ( RTSS ) , a sum of 6 individual symptom scores : sneezing , runny nose , itchy nose , nasal congestion , watery eyes , and itchy eyes . Secondary end points included rescue medication intake , individual scores , and safety . RESULTS The intent-to-treat population included 266 children ( mean age , 10.9 + /- 3.22 years ) . The RTSS for the 300-IR group was highly significantly different from that of the placebo group ( P = .001 ) . The 300-IR group showed a mean improvement for the RTSS of 28.0 % over that seen with placebo and a median improvement of 39.3 % . Significant differences between the 300-IR and placebo groups were also observed regarding rescue medication score and proportion of days using rescue medication during the pollen season ( P = .0064 and P = .0146 , respectively ) . Adverse events were generally mild or moderate in intensity and expected . No serious side effects were reported . CONCLUSION Five-grass-pollen SLIT tablets ( 300 IR ) reduce both symptom scores and rescue medication use in children and adolescents with grass pollen-related rhinoconjunctivitis Background : Data supporting a carry‐over effect with sublingual immunotherapy ( SLIT ) are scarce . This r and omized , double‐blind , placebo‐controlled study evaluated the efficacy , carry‐over effect and safety of grass pollen SLIT using co‐seasonal treatment IMPORTANCE The house dust mite ( HDM ) sublingual allergen immunotherapy ( SLIT ) tablet is a potential novel treatment option for HDM allergy-related asthma . OBJECTIVES To evaluate the efficacy and adverse events of the HDM SLIT tablet vs placebo for asthma exacerbations during an inhaled corticosteroid ( ICS ) reduction period . DESIGN , SETTING S , AND PARTICIPANTS Double-blind , r and omized , placebo-controlled  trial conducted between August 2011 and April 2013 in 109 European trial sites . The trial included 834 adults with HDM allergy-related asthma not well controlled by ICS or combination products , and with HDM allergy-related rhinitis . Key exclusion criteria were FEV1 less than 70 % of predicted value or hospitalization due to asthma within 3 months before r and omization .  Efficacy was assessed during the last 6 months of the trial when ICS was reduced by 50 % for 3 months and then completely withdrawn for 3 months . INTERVENTIONS 1:1:1 r and omization to once-daily treatment with placebo ( n = 277 ) or HDM SLIT tablet ( dosage groups : 6 SQ-HDM [ n = 275 ] or 12 SQ-HDM [ n = 282 ] ) in addition to ICS and the short-acting β2-agonist salbutamol . MAIN OUTCOMES AND MEASURES Primary outcome was time to first moderate or severe asthma exacerbation during the ICS reduction period . Secondary outcomes were deterioration in asthma symptoms , change in allergen-specific immunoglobulin G4 ( IgG4 ) , change in asthma control or asthma quality -of-life question naires , and adverse events . RESULTS Among 834 r and omized patients ( mean age , 33 years [ range , 17 - 83 ] ; women , 48 % ) , 693 completed the study . The 6 SQ-HDM and 12 SQ-HDM doses both significantly reduced the risk of a moderate or severe asthma exacerbation compared with placebo ( hazard ratio [ HR ] : 0.72 [ 95 % CI , 0.52 - 0.99 ] for the 6 SQ-HDM group , P = .045 , and 0.69 [ 95 % CI , 0.50 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) . The absolute risk differences based on the observed data ( full analysis set ) in the active groups vs the placebo group were 0.09 ( 95 % CI , 0.01 - 0.15 ) for the 6 SQ-HDM group and 0.10 ( 95 % CI , 0.02 - 0.16 ) for the 12 SQ-HDM group . There was no significant difference between the 2 active groups . Compared with placebo , there was a reduced risk of an exacerbation with deterioration in asthma symptoms ( HR , 0.72 [ 95 % CI , 0.49 - 1.02 ] for the 6 SQ-HDM group , P = .11 , and 0.64 [ 95 % CI , 0.42 - 0.96 ] for the 12 SQ-HDM group , P = .03 ) and a significant increase in allergen-specific IgG4 . However , there was no significant difference for change in asthma control question naire or asthma quality -of-life question naire for either dose . There were no reports of severe systemic allergic reactions . The most frequent adverse events were mild to moderate oral pruritus ( 13 % for the 6 SQ-HDM group , 20 % for the 12 SQ-HDM group , and 3 % for the placebo group ) , mouth edema , and throat irritation . CONCLUSIONS AND RELEVANCE Among adults with HDM allergy-related asthma not well controlled by ICS , the addition of HDM SLIT to maintenance medications improved time to first moderate or severe asthma exacerbation during ICS reduction , with an estimated absolute reduction at 6 months of 9 to 10 percentage points ; the reduction was primarily due to an effect on moderate exacerbations . Treatment-related adverse events were common at both active doses . Further studies are needed to assess long-term efficacy and safety . TRIAL REGISTRATION clinical trialsregister.eu Identifier : 2010 - 018621 - 19 BACKGROUND The 5-grass pollen sublingual tablet has been approved for the treatment of grass pollen-induced allergic rhinoconjunctivitis in subjects with or without intermittent asthma . OBJECTIVE To provide a comprehensive analysis of the safety profile of the 5-grass tablet on the basis of pooled data from 8 clinical trials . METHODS Subjects ( 5 - 65 years old ) with medically confirmed grass pollen-induced allergic rhinoconjunctivitis were included in the double-blind studies . Those with intermittent asthma not requiring treatment other than inhaled beta-2 agonists could participate . R and omized subjects received a 5-grass or placebo tablet daily 2 or 4 months preseasonally and coseasonally ( 5 single-season studies , over 3 years in a long-term study ) or outside the season ( phase I studies ) . Adverse events were pooled and analyzed descriptively . RESULTS Among 2,512 subjects enrolled , 1,514 received the 5-grass tablet . A total of 1,038 adults and 154 pediatric ( 5 - 17 years old ) subjects were treated with the 300 Index of Reactivity dose ( vs 840 and 158 placebo recipients , respectively ) ; 17 % had intermittent asthma , and 62 % were polysensitized . Adverse reactions ( ADRs ) reported in more than 10 % of actively treated subjects were mild or moderate application-site reactions , for example , oral pruritus 25 % ( placebo 4 % ) and throat irritation 21 % ( placebo 3 % ) . These generally occurred during the first week of treatment and decreased over time . They led to discontinuation in less than 2.5 % of subjects . None of the 3 serious ADRs were reports of anaphylaxis . No notable differences were detected in terms of incidence , nature , and severity of ADRs between adult and pediatric population s , nor between subjects with or without asthma . CONCLUSIONS The pooled analysis in 1,514 subjects from 8 clinical studies demonstrates that the 5-grass pollen sublingual tablet has a similar good safety profile in adult and pediatric patients with or without mild , intermittent asthma Background : The SQ house dust mite ( HDM ) SLIT-tablet ( ALK , Denmark ) addresses the underlying cause of HDM respiratory allergic disease , and a clinical effect has been demonstrated for both HDM allergic rhinitis and allergic asthma . Here , we present pooled safety data from an adult population with HDM respiratory allergy , with particular focus on the impact of asthma on the SQ HDM SLIT-tablet tolerability profile . Methods : Safety data from 2 r and omised double-blind , placebo-controlled clinical trials were included : MT-04 : 834 adults with HDM allergic asthma not well controlled by inhaled corticosteroids and with HDM allergic rhinitis , and MT-06 : 992 adults with moderate-to-severe HDM allergic rhinitis despite the use of allergy pharmacotherapy and with or without asthma . Results : The proportion of subjects experiencing adverse events ( AEs ) was greater in the active treatment group ( 12 SQ-HDM ; 73 % of subjects ) compared to placebo ( 53 % ) . The most common treatment-related AEs were local allergic reactions . No AEs were reported as systemic allergic reactions . Regardless of asthma status , most AEs were mild or moderate ( > 97 % of AEs ) and the frequency of serious AEs was low . Subgroup analysis revealed no statistically significant difference in the risk of experiencing moderate or severe treatment-related AEs for subjects with asthma compared to subjects without asthma ( p = 0.88 ) . In addition , subjects with partly controlled or uncontrolled asthma were no more likely to experience moderate or severe treatment-related AEs than subjects with controlled asthma ( p = 0.42 ) . Conclusion : The SQ HDM SLIT-tablet is well tolerated , and the safety profile was comparable for subjects with HDM respiratory allergic disease irrespective of asthma status BACKGROUND Treatment with SQ house dust mite ( HDM ) sublingual immunotherapy ( SLIT ) tablet is effective for HDM respiratory allergic disease , but data on long-term effects are lacking . OBJECTIVE Post hoc analyses were conducted to determine the long-term effect of SQ HDM SLIT-tablet on nasal , ocular , and cough symptoms 1 year after discontinuation of treatment . METHODS Study participants underwent  environmental exposure chamber ( EEC ) challenges at baseline and week 24 in a r and omized , placebo-controlled , double-blind trial ( NCT01644617 ) during which participants received daily 12 SQ- 
    Output:
    
Data from the majority of properly controlled clinical trials demonstrate that SLIT is effective not only with short-term use ( first year ) but also with long-term use ( up to the third year of active therapy ) , for treating ARDs in children and adults .
Both continuous and discontinuous schemes of administration showed significant reductions in symptom and medication scores .
Moreover , a SLIT-induced disease-modifying effect has been documented mainly with grass pollen extracts , since improvement is maintained during at least 2 years of follow-up after a 3-year treatment period .
This therapy is also safe , producing only a few mainly local and mild-to-moderate adverse events , and usually self-limited in time .