***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 The 300IR ( index of reactivity ) 5-grass pollen tablet has favorable short-term and sustained clinical efficacy in patients with grass pollen-induced allergic rhinoconjunctivitis ( ARC ) . Here , we report maintenance of efficacy and safety over 2 years following treatment discontinuation . Methods R and omized , double-blind , placebo-controlled , parallel-group , multicenter Phase 3 trial in patients aged 18–50 years with ARC . During study years 1–3 , patients received a daily sublingual tablet containing either 300IR 5-grass pollen extract or placebo , according to a discontinuous pre- and coseasonal protocol . Study years 4 and 5 were treatment-free . In response to health authorities ’ recommendations , the daily combined score ( DCS ) was assessed in a post-hoc analysis as the efficacy endpoint . Components of the DCS were daily rhinoconjunctivitis total symptom score ( DRTSS ) and daily rescue medication score ( DRMS ) . Results 633 patients with ARC were r and omized to placebo ( n = 219 ) or 300IR 5-grass pollen tablet , beginning 4 months ( 4 M , n = 207 ) or 2 months ( 2 M , n = 207 ) prior to the estimated start of the grass pollen season and continuing until season ’s end . During the first post-treatment year , a statistically significant difference versus placebo in least squares ( LS ) mean DCS was noted in patients previously receiving active treatment ( 300IR ( 2 M ) point estimate : −0.16 , 95 % confidence interval ( CI95 % ) : [ −0.26 , −0.06 ] , p = 0.0019 ; −31.1 % ; 300IR ( 4 M ) point estimate : −0.13 , CI95 % : [ −0.23 , −0.03 ] , p = 0.0103 , −25.3 % ) . During the second post-treatment year , patients in the 300IR ( 4 M ) group , but not the 300IR ( 2 M ) group , showed a statistically significant difference in LS mean DCS versus placebo ( point estimate : −0.11 , CI95 % : [ −0.21 ; 0.00 ] , p = 0.0478 , −28.1 % ) . This significant efficacy seen during the post-treatment years in patients previously treated with 5-grass pollen tablet compared favorably with that during the 3 prior years of active treatment . A statistically significant difference versus placebo was also noted in secondary efficacy measures in both post-treatment years ( except for DRTSS in year 5 ) . In the absence of any active treatment , the safety profile was similar in the active groups versus placebo group during either post-treatment year . Conclusions In adults with grass pollen-associated ARC  , 5-grass pollen tablet therapy beginning 4 months before the pollen season and continuing to season ’s end demonstrated efficacy across all variables during active treatment , and this effect was prolonged for up to 2 years post-treatment . Trial registration Clinical Trials.gov identifier : NCT00418379 BACKGROUND Sublingual immunotherapy is well tolerated and data suggest its effectiveness for the treatment of allergic rhinitis in adults , but it lacks optimum dose definition . OBJECTIVE To assess the efficacy , safety , and optimal dose of grass pollen tablets for immunotherapy of patients with allergic rhinoconjunctivitis . METHODS In this multinational , r and omized , double-blind , placebo-controlled study , 628 adults with grass pollen rhinoconjunctivitis ( confirmed by positive skin prick test and serum-specific IgE ) received 1 of 3 doses of a st and ardized 5-grass pollen extract , or placebo , administered sublingually using a once-daily tablet formulation . The treatment was initiated 4 months before the estimated pollen season and continued throughout the season . The primary outcome was Rhinoconjunctivitis Total Symptom Score ; secondary outcomes included 6 individual symptom scores , rescue medication use , quality of life , and safety assessment s. RESULTS Both the 300-index of reactivity ( IR ) and 500-IR doses significantly reduced mean Rhinoconjunctivitis Total Symptom Score ( 3.58 + /- 3.0 , P = .0001 ; and 3.74 + /- 3.1 , P = .0006 , respectively ) compared with placebo ( 4.93 + /- 3.2 ) in the intent-to-treat and per- protocol analyses . The 100-IR group ( 4.70 + /- 3.1 ) score was not significantly different from placebo . Analysis of all secondary efficacy variables ( sneezing , runny nose , itchy nose , nasal congestion , watery eyes , itchy eyes , rescue medication usage , and quality of life ) confirmed the efficacy of the 300-IR and 500-IR doses . No serious side effects were reported . CONCLUSION In the first pollen season , the efficacy and safety of sublingual immunotherapy with grass tablets was confirmed . The 300-IR and 500-IR doses both demonstrated significant efficacy compared with placebo . CLINICAL IMPLICATION S The risk-benefit ratio favors the use of 300-IR tablets for clinical practice BACKGROUND Allergen immunotherapy ( AIT ) has been thoroughly documented in r and omized controlled trials ( RCTs ) . It is the only immune-modifying and causal treatment available for patients suffering from IgE-mediated diseases such as allergic rhinoconjunctivitis , allergic asthma and insect sting allergy . However , there is a high degree of clinical and method ological heterogeneity among the endpoints in clinical studies on AIT , for both subcutaneous and sublingual immunotherapy ( SCIT and SLIT ) . At present , there are no commonly accepted st and ards for defining the optimal outcome parameters to be used for both primary and secondary endpoints . METHODS As elaborated by a Task Force ( TF ) of the European Academy of Allergy and Clinical Immunology ( EAACI ) Immunotherapy Interest Group , this Position Paper evaluates the currently used outcome parameters in different RCTs and also aims to provide recommendations for the optimal endpoints in future AIT trials for allergic rhinoconjunctivitis . RESULTS Based on a thorough literature review , the TF members have outlined recommendations for nine domains of clinical outcome measures . As the primary outcome , the TF recommends a homogeneous combined symptom and medication score ( CSMS ) as a simple and st and ardized method that balances both symptoms and the need for antiallergic medication in an equally weighted manner . All outcomes , grouped into nine domains , are review ed . CONCLUSION A st and ardized and globally harmonized method for analysing the clinical efficacy of AIT products in RCTs is required . The EAACI TF highlights the CSMS as the primary endpoint for future RCTs in AIT for allergic rhinoconjunctivitis Background In clinical trials , the efficacy of immunotherapy for allergic rhinoconjunctivitis symptoms is often evaluated with the average Rhinoconjunctivitis Total Symptom Score ( ARTSS ) . Effective treatment is associated with a lower ARTSS vs. placebo but use of rescue medication to alleviate symptoms reduces the RTSS and decreases the mean difference between active treatment and placebo groups BACKGROUND Previous trials have demonstrated the efficacy , safety , and optimal dosage of the 5-grass pollen sublingual tablet for adults and children with grass pollen-induced allergic rhinoconjunctivitis . OBJECTIVES We sought to evaluate the efficacy and safety of 300 index of reactivity ( IR ) 5-grass pollen sublingual tablet in US adults . METHODS Adults with grass pollen allergy and Rhinoconjunctivitis Total Symptom Scores of 12 or greater ( scale , 0 - 18 ) during the previous grass pollen season were r and omized in a double-blind , placebo-controlled study to receive 300IR 5-grass pollen sublingual tablet or placebo starting 4 months before and continuing through the pollen season . The primary efficacy end point was the daily Combined Score ( CS ; scale , 0 - 3 ) , which integrates symptoms and rescue medication use . RESULTS Four hundred seventy-three participants were r and omized . The mean daily CS over the pollen period was significantly lower in the active treatment group versus the placebo group ( least-squares mean difference : -0.13 ; 95 % CI , -0.19 to -0.06 ; P = .0003 ; relative reduction : 28.2 % ; 95 % CI , 13.0 % to 43.4 % ) . In placebo-treated participants , the daily CS least-squares mean was 0.32 in the subgroup with baseline timothy grass-specific serum IgE of less than 0.1 kU/L ( n = 23 ) and 0.46 in those with baseline timothy grass-specific serum IgE of 0.1 kU/L or greater ( n = 204 ) . The most frequent reported adverse events were oral pruritus , throat irritation , and nasopharyngitis . There were no reports of anaphylaxis , and no actively treated participant received epinephrine . CONCLUSION In US adults with grass pollen-induced allergic rhinoconjunctivitis , preseasonal and coseasonal treatment with 300IR 5-grass pollen sublingual tablet demonstrated clinical ly meaningful efficacy , especially in study subjects with measurable timothy grass-specific serum IgE. Use of 300IR 5-grass pollen sublingual tablet was safe and well tolerated . A requirement for a measurable level of allergen-specific serum IgE should be considered in future studies in this field BACKGROUND The main aim of specific immunotherapy is sustained effect due to changes in the immune system that can be demonstrated only in long-term trials . OBJECTIVE To investigate sustained efficacy and disease modification in a 5-year double-blind , placebo-controlled trial , including 2 years of blinded follow-up after completion of a 3-year period of treatment , with the SQ-st and ardized grass allergy immunotherapy tablet , Grazax ( Phleum pratense 75,000 SQ-T/2,800 BAU,(∗ ) ALK , Denmark ) or placebo . METHODS A r and omized , double-blind , placebo-controlled , multinational , phase III trial included adults with a history of moderate-to-severe grass pollen-induced allergic rhinoconjunctivitis , with or without asthma , inadequately controlled by symptomatic medications . Two hundred thirty-eight participants completed the trial . End points included rhinoconjunctivitis symptom and medication scores , combined scores , asthma symptom and medication scores , quality of life , days with severe symptoms , immunologic end points , and safety parameters . RESULTS The mean rhinoconjunctivitis daily symptom score was reduced by 25 % to 36 % ( P ≤ .004 ) in the grass allergy immunotherapy tablet group compared with the placebo group over the 5 grass pollen seasons covered by the trial . The rhinoconjunctivitis DMS was reduced by 20 % to 45 % ( P ≤ .022 for seasons 1 - 4 ; P = .114 for season 5 ) , and the weighted rhinoconjunctivitis combined score was reduced by 27 % to 41 % ( P ≤ .003 ) in favor of active treatment . The percentage of days with severe symptoms during the peak grass pollen exposure was in all seasons lower in the active group than in the placebo group , with relative differences of 49 % to 63 % ( P ≤ .0001 ) . Efficacy was supported by long-lasting significant effects on the allergen-specific antibody response . No safety issues were identified . CONCLUSION The results confirm disease modification by SQ-st and ardized grass allergy immunotherapy tablet in addition to effective symptomatic treatment of allergic rhinoconjunctivitis BACKGROUND Seasonal allergic rhinitis is common and troublesome . Sublingual immunotherapy ( SLIT ) has been proposed as an alternative to injection immunotherapy and might offer some advantages if it were effective and practical in a community setting . OBJECTIVES To assess the efficacy and side-effect profile of SLIT in patients with summer hay fever uncontrolled on current st and ard medication . To assess the feasibility of delivering SLIT in a United Kingdom general practice setting . METHODS Double-blind , placebo-controlled study in 186 patients with severe summer hay fever identified from 16 United Kingdom general practice s. After a baseline year to ensure balanced groups , subjects were r and omized , and SLIT was given for 1 or 2 years and compared with placebo . The principal outcome measure was symptoms as recorded on diary cards . Secondary criteria were skin and conjunctival reactivity , allergen-specific IgE and IgG 4 , and the frequency and severity of adverse effects . RESULTS One hundred thirty-six subjects completed the study . After 1 year , no significant differences were found between actively treated subjects and the placebo group . After the second year of therapy , subjects who had received 2 years treatment were 6.8 times more likely to show a reduction in nose running ( P < .001 ) and 2.4 times more likely to have reduced sneezing ( P < .05 ) compared with subjects in the placebo group . Benefits for nasal blockage were found at the peak pollen season and were similar in both actively treated groups . CONCLUSION Sublingual immunotherapy can be 
    Output:
    
The authors analyzed SSs and MSs separately as the primary outcomes for SLIT , whereas a score combining symptoms and rescue medication use is generally favored as the primary outcome by both regulatory agencies and professional societies .