human
***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 IL-5 , a mediator of eosinophil activity , is an important potential treatment target in patients with uncontrolled asthma . The efficacy of reslizumab , a humanized anti-human IL-5 monoclonal antibody , has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma , particularly those with eosinophils < 400 cells/μL. METHODS Patients were r and omly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks . The primary end point was the change in FEV1 from baseline to week 16 . Secondary measures included Asthma Control Question naire-7 ( ACQ-7 ) scores , use of short-acting β-agonists ( SABAs ) , and FVC . RESULTS Four hundred ninety-two patients received ≥ 1 dose of placebo ( n = 97 ) or reslizumab ( n = 395 ) . In the overall population , mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo , and no significant relationship was detected between treatment , baseline blood eosinophils and change in FEV1 . In the subgroup of patients with baseline eosinophils < 400 cells/μL , patients treated with reslizumab showed no significant improvement in FEV1 compared with those receiving placebo . In the subgroup with eosinophils ≥ 400 cells/μL , however , treatment with reslizumab was associated with much larger improvements in FEV1 , ACQ-7 , rescue SABA use , and FVC compared with the placebo group . Reslizumab was well tolerated , with fewer overall adverse events compared with placebo ( 55 % vs 73 % ) . CONCLUSIONS Reslizumab was well tolerated in patients with inadequately controlled asthma . Clinical ly meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01508936 ; URL : www . clinical trials.gov BACKGROUND Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids . One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype . We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity . METHODS We conducted a r and omized , double-blind , placebo-controlled study of lebrikizumab , a monoclonal antibody to interleukin-13 , in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy .  The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second ( FEV(1 ) ) from baseline to week 12 . Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks . Patient subgroups were prespecified according to baseline type 2 helper T-cell ( Th2 ) status ( assessed on the basis of total IgE level and blood eosinophil count ) and serum periostin level . RESULTS At baseline , patients had a mean FEV(1 )  that was 65 % of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day ; 80 % were also taking a long-acting beta-agonist . At week 12 , the mean increase in FEV(1 ) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.02 ) . Among patients in the high-periostin subgroup , the increase from baseline FEV(1 ) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.03 ) . Among patients in the low-periostin subgroup , the increase from baseline FEV(1 ) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.61 ) . Musculoskeletal side effects were more common with lebrikizumab than with placebo ( 13.2 % vs. 5.4 % , P = 0.045 ) . CONCLUSIONS Lebrikizumab treatment was associated with improved lung function . Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels . ( Funded by Genentech ; Clinical Trials.gov number , NCT00930163 . ) BACKGROUND Benralizumab is an anti-eosinophilic , anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe , uncontrolled asthma . We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories . METHODS This study is a pooled analysis of the results from the r and omised , double-blind , placebo-controlled SIROCCO ( NCT01928771 ) and CALIMA ( NCT01914757 ) phase 3 studies . In these studies , patients with severe , uncontrolled asthma were r and omly assigned ( 1:1:1 ) to receive subcutaneous benralizumab 30 mg , either every 4 weeks or every 8 weeks ( with first three doses given every 4 weeks ) , or placebo every 4 weeks . The primary endpoint was annual exacerbation rate ( AER ) ratio versus placebo , analysed by baseline eosinophil counts ( ≥0 , ≥150 , ≥300 , or ≥450 cells per μL ) and by number of exacerbations ( two vs three or more ) during the year before enrolment . The analyses were done in accordance with the intention-to-treat principle . FINDINGS Of 2295 patients , 756 received benralizumab every 4 weeks , 762 received benralizumab every 8 weeks , and 777 patients received placebo . AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 ( 95 % CI 1·05 - 1·28 ) in patients who received placebo versus 0·75 ( 0·66 - 0·84 ) in patients who received benralizumab every 8 weeks ( rate ratio 0·64 , 0·55 - 0·75 ; p<0·0001 ) . In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL , AER was 0·73 ( 0·65 - 0·82 ) ; rate ratio versus placebo was 0·63 ( 0·54 - 0·74 ; p<0·0001 ) . The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups . Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations . INTERPRETATION These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe , uncontrolled , eosinophilic asthma . FUNDING AstraZeneca BACKGROUND Mepolizumab , an anti-interleukin-5 monoclonal antibody approved as add-on therapy to st and ard of care for patients with severe eosinophilic asthma , has been shown in previous studies to reduce exacerbations and dependency on oral corticosteroids compared with placebo . We aim ed to further assess mepolizumab in patients with severe eosinophilic asthma by examining its effect on health-related quality of life ( HRQOL ) . METHODS We did a r and omised , double-blind , placebo-controlled , parallel-group , multicentre , phase 3b trial ( MUSCA ) in 146 hospitals or research centres in 19 countries worldwide . Eligible participants were patients aged 12 years or older with severe eosinophilic asthma and a history of at least two exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines . Exclusion criteria included current smokers or former smokers with a history of at least ten pack-years . We r and omly assigned participants ( 1:1 ) by country to receive a subcutaneous injection of either mepolizumab 100 mg or placebo , plus st and ard of care , every 4 weeks for 24 weeks ( the final dose was given at week 20 ) . We did the r and omisation using an interactive voice response system and a central ised , computer-generated , permuted-block design of block size six . The two treatments were identical in appearance and administered in a masked manner ; patients , investigators , other site staff and the entire study team including those assessing outcomes data were also masked to group assignment . The primary endpoint was the mean change from baseline in the St George 's Respiratory Question naire ( SGRQ ) total score at week 24 in the modified intention-to-treat ( modified ITT ) population ( analysed according to their r and omly assigned treatment ) . Safety was assessed in all patients who received at least one dose of trial medication ( analysed according to the actual treatment received ) . This trial is registered with Clinical Trials.gov , number NCT02281318 . FINDINGS We recruited patients between Dec 11 , 2014 , and Nov 20 , 2015 , and the study was undertaken between Dec 11 , 2014 , and June 10 , 2016 . The modified ITT population comprised 274 patients assigned to mepolizumab 100 mg and 277 assigned to placebo . Mepolizumab versus placebo showed significant improvements at week 24 from baseline in SGRQ total score ( least squares mean [ SE ] change from baseline -15·6 ( 1·0 ) vs -7·9 ( 1·0 ) , a treatment difference of -7·7 ( 95 % CI -10·5 to -4·9 ; p<0·0001 ) . No deaths occurred during the study . 192 ( 70 % ) of 273 patients who received mepolizumab and 207 ( 74 % ) of 278 who received placebo reported at least one on-treatment adverse event , the most common of which were headache ( in 45 [ 16 % ] given mepolizumab vs 59 [ 21 % ] given placebo ) and nasopharyngitis ( in 31 [ 11 % ] given mepolizumab vs 46 [ 17 % ] given placebo ) . 15 ( 5 % ) and 22 ( 8 % ) patients had an on-treatment serious adverse event in the mepolizumab and placebo groups , respectively ; the most common was asthma in both groups ( in three [ 1 % ] given mepolizumab vs nine [ 3 % ] given placebo ) . INTERPRETATION Mepolizumab was associated with significant improvements in HRQOL in patients with severe eosinophilic asthma , and had a safety profile similar to that of placebo . These results add to and support the use of mepolizumab as a favourable add-on treatment option to st and ard of care in patients with severe eosinophilic asthma . FUNDING GlaxoSmithKline BACKGROUND Benralizumab is a humanised , anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils , reduces asthma exacerbations , and improves lung function for patients with severe eosinophilic asthma . The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate , persistent asthma . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial , we recruited patients aged 18 - 75 years , weighing at least 40 kg , and with a postbronchodilator reversibility in forced expiratory volume in 1 s ( FEV1 ) of at least 12 % at screening , from 52 clinical research centres in six countries . Patients must have been receiving either low- to medium-dosage inhaled corticosteroids ( ICS ) or low-dosage ICS plus long-acting β2 agonist fixed-combination therapy at screening , had a morning prebronchodilator FEV1 of more than 50 % to 90 % predicted at screening , and had one or more of the following symptoms within the 7 days before r and omisation : a daytime or night-time asthma symptom score of at least 1 for at least 2 days , rescue short-acting β2 agonist use for at least 2 days , or night-time awakenings due to asthma for at least one night . We converted patients ' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients ' respective countries and r and omly allocated them ( 1 
    Output:
    
agent
***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 IL-5 , a mediator of eosinophil activity , is an important potential treatment target in patients with uncontrolled asthma . The efficacy of reslizumab , a humanized anti-human IL-5 monoclonal antibody , has been characterized in patients with blood eosinophils ≥ 400 cells/μL. This study further characterizes the efficacy and safety of reslizumab in patients with poorly-controlled asthma , particularly those with eosinophils < 400 cells/μL. METHODS Patients were r and omly assigned to intravenous reslizumab 3.0 mg/kg or placebo once every 4 weeks for 16 weeks . The primary end point was the change in FEV1 from baseline to week 16 . Secondary measures included Asthma Control Question naire-7 ( ACQ-7 ) scores , use of short-acting β-agonists ( SABAs ) , and FVC . RESULTS Four hundred ninety-two patients received ≥ 1 dose of placebo ( n = 97 ) or reslizumab ( n = 395 ) . In the overall population , mean FEV1 change from baseline to week 16 was not significantly different between reslizumab and placebo , and no significant relationship was detected between treatment , baseline blood eosinophils and change in FEV1 . In the subgroup of patients with baseline eosinophils < 400 cells/μL , patients treated with reslizumab showed no significant improvement in FEV1 compared with those receiving placebo . In the subgroup with eosinophils ≥ 400 cells/μL , however , treatment with reslizumab was associated with much larger improvements in FEV1 , ACQ-7 , rescue SABA use , and FVC compared with the placebo group . Reslizumab was well tolerated , with fewer overall adverse events compared with placebo ( 55 % vs 73 % ) . CONCLUSIONS Reslizumab was well tolerated in patients with inadequately controlled asthma . Clinical ly meaningful effects on lung function and symptom control were not seen in patients unselected for baseline eosinophils . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01508936 ; URL : www . clinical trials.gov BACKGROUND Many patients with asthma have uncontrolled disease despite treatment with inhaled glucocorticoids . One potential cause of the variability in response to treatment is heterogeneity in the role of interleukin-13 expression in the clinical asthma phenotype . We hypothesized that anti-interleukin-13 therapy would benefit patients with asthma who had a pretreatment profile consistent with interleukin-13 activity . METHODS We conducted a r and omized , double-blind , placebo-controlled study of lebrikizumab , a monoclonal antibody to interleukin-13 , in 219 adults who had asthma that was inadequately controlled despite inhaled glucocorticoid therapy .  The primary efficacy outcome was the relative change in prebronchodilator forced expiratory volume in 1 second ( FEV(1 ) ) from baseline to week 12 . Among the secondary outcomes was the rate of asthma exacerbations through 24 weeks . Patient subgroups were prespecified according to baseline type 2 helper T-cell ( Th2 ) status ( assessed on the basis of total IgE level and blood eosinophil count ) and serum periostin level . RESULTS At baseline , patients had a mean FEV(1 )  that was 65 % of the predicted value and were taking a mean dose of inhaled glucocorticoids of 580 μg per day ; 80 % were also taking a long-acting beta-agonist . At week 12 , the mean increase in FEV(1 ) was 5.5 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.02 ) . Among patients in the high-periostin subgroup , the increase from baseline FEV(1 ) was 8.2 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.03 ) . Among patients in the low-periostin subgroup , the increase from baseline FEV(1 ) was 1.6 percentage points higher in the lebrikizumab group than in the placebo group ( P = 0.61 ) . Musculoskeletal side effects were more common with lebrikizumab than with placebo ( 13.2 % vs. 5.4 % , P = 0.045 ) . CONCLUSIONS Lebrikizumab treatment was associated with improved lung function . Patients with high pretreatment levels of serum periostin had greater improvement in lung function with lebrikizumab than did patients with low periostin levels . ( Funded by Genentech ; Clinical Trials.gov number , NCT00930163 . ) BACKGROUND Benralizumab is an anti-eosinophilic , anti-interleukin-5 receptor α monoclonal antibody that has been shown to significantly reduce asthma exacerbations and improve lung function for patients with severe , uncontrolled asthma . We further explored the efficacy of benralizumab for patients with different baseline blood eosinophil thresholds and exacerbation histories . METHODS This study is a pooled analysis of the results from the r and omised , double-blind , placebo-controlled SIROCCO ( NCT01928771 ) and CALIMA ( NCT01914757 ) phase 3 studies . In these studies , patients with severe , uncontrolled asthma were r and omly assigned ( 1:1:1 ) to receive subcutaneous benralizumab 30 mg , either every 4 weeks or every 8 weeks ( with first three doses given every 4 weeks ) , or placebo every 4 weeks . The primary endpoint was annual exacerbation rate ( AER ) ratio versus placebo , analysed by baseline eosinophil counts ( ≥0 , ≥150 , ≥300 , or ≥450 cells per μL ) and by number of exacerbations ( two vs three or more ) during the year before enrolment . The analyses were done in accordance with the intention-to-treat principle . FINDINGS Of 2295 patients , 756 received benralizumab every 4 weeks , 762 received benralizumab every 8 weeks , and 777 patients received placebo . AER among patients with baseline blood eosinophil counts of at least 0 cells per μL was 1·16 ( 95 % CI 1·05 - 1·28 ) in patients who received placebo versus 0·75 ( 0·66 - 0·84 ) in patients who received benralizumab every 8 weeks ( rate ratio 0·64 , 0·55 - 0·75 ; p<0·0001 ) . In patients who received benralizumab every 4 weeks who had eosinophil counts of 0 or more cells per μL , AER was 0·73 ( 0·65 - 0·82 ) ; rate ratio versus placebo was 0·63 ( 0·54 - 0·74 ; p<0·0001 ) . The extent to which exacerbation rates were reduced increased with increasing blood eosinophil thresholds and with greater exacerbation history in patients in the 4-weekly and 8-weekly benralizumab groups . Greater improvements in AER were seen with benralizumab compared with placebo for patients with a combination of high blood eosinophil thresholds and a history of more frequent exacerbations . INTERPRETATION These results will help to guide clinicians when they are deciding whether to use benralizumab to treat patients with severe , uncontrolled , eosinophilic asthma . FUNDING AstraZeneca BACKGROUND Mepolizumab , an anti-interleukin-5 monoclonal antibody approved as add-on therapy to st and ard of care for patients with severe eosinophilic asthma , has been shown in previous studies to reduce exacerbations and dependency on oral corticosteroids compared with placebo . We aim ed to further assess mepolizumab in patients with severe eosinophilic asthma by examining its effect on health-related quality of life ( HRQOL ) . METHODS We did a r and omised , double-blind , placebo-controlled , parallel-group , multicentre , phase 3b trial ( MUSCA ) in 146 hospitals or research centres in 19 countries worldwide . Eligible participants were patients aged 12 years or older with severe eosinophilic asthma and a history of at least two exacerbations requiring treatment in the previous 12 months before screening despite regular use of high-dose inhaled corticosteroids plus other controller medicines . Exclusion criteria included current smokers or former smokers with a history of at least ten pack-years . We r and omly assigned participants ( 1:1 ) by country to receive a subcutaneous injection of either mepolizumab 100 mg or placebo , plus st and ard of care , every 4 weeks for 24 weeks ( the final dose was given at week 20 ) . We did the r and omisation using an interactive voice response system and a central ised , computer-generated , permuted-block design of block size six . The two treatments were identical in appearance and administered in a masked manner ; patients , investigators , other site staff and the entire study team including those assessing outcomes data were also masked to group assignment . The primary endpoint was the mean change from baseline in the St George 's Respiratory Question naire ( SGRQ ) total score at week 24 in the modified intention-to-treat ( modified ITT ) population ( analysed according to their r and omly assigned treatment ) . Safety was assessed in all patients who received at least one dose of trial medication ( analysed according to the actual treatment received ) . This trial is registered with Clinical Trials.gov , number NCT02281318 . FINDINGS We recruited patients between Dec 11 , 2014 , and Nov 20 , 2015 , and the study was undertaken between Dec 11 , 2014 , and June 10 , 2016 . The modified ITT population comprised 274 patients assigned to mepolizumab 100 mg and 277 assigned to placebo . Mepolizumab versus placebo showed significant improvements at week 24 from baseline in SGRQ total score ( least squares mean [ SE ] change from baseline -15·6 ( 1·0 ) vs -7·9 ( 1·0 ) , a treatment difference of -7·7 ( 95 % CI -10·5 to -4·9 ; p<0·0001 ) . No deaths occurred during the study . 192 ( 70 % ) of 273 patients who received mepolizumab and 207 ( 74 % ) of 278 who received placebo reported at least one on-treatment adverse event , the most common of which were headache ( in 45 [ 16 % ] given mepolizumab vs 59 [ 21 % ] given placebo ) and nasopharyngitis ( in 31 [ 11 % ] given mepolizumab vs 46 [ 17 % ] given placebo ) . 15 ( 5 % ) and 22 ( 8 % ) patients had an on-treatment serious adverse event in the mepolizumab and placebo groups , respectively ; the most common was asthma in both groups ( in three [ 1 % ] given mepolizumab vs nine [ 3 % ] given placebo ) . INTERPRETATION Mepolizumab was associated with significant improvements in HRQOL in patients with severe eosinophilic asthma , and had a safety profile similar to that of placebo . These results add to and support the use of mepolizumab as a favourable add-on treatment option to st and ard of care in patients with severe eosinophilic asthma . FUNDING GlaxoSmithKline BACKGROUND Benralizumab is a humanised , anti-interleukin 5 receptor α monoclonal antibody that directly and rapidly depletes eosinophils , reduces asthma exacerbations , and improves lung function for patients with severe eosinophilic asthma . The objective of this trial was to assess the safety and efficacy of benralizumab for patients with mild to moderate , persistent asthma . METHODS In this r and omised , double-blind , placebo-controlled , phase 3 trial , we recruited patients aged 18 - 75 years , weighing at least 40 kg , and with a postbronchodilator reversibility in forced expiratory volume in 1 s ( FEV1 ) of at least 12 % at screening , from 52 clinical research centres in six countries . Patients must have been receiving either low- to medium-dosage inhaled corticosteroids ( ICS ) or low-dosage ICS plus long-acting β2 agonist fixed-combination therapy at screening , had a morning prebronchodilator FEV1 of more than 50 % to 90 % predicted at screening , and had one or more of the following symptoms within the 7 days before r and omisation : a daytime or night-time asthma symptom score of at least 1 for at least 2 days , rescue short-acting β2 agonist use for at least 2 days , or night-time awakenings due to asthma for at least one night . We converted patients ' ICS treatments to 180 μg or 200 μg budesonide dry powder inhaler twice daily for the entire duration of the study using the approved dosages in the patients ' respective countries and r and omly allocated them ( 1 
    Output:
    