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 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 . ) Objective Interleukin 13 ( IL-13 ) is thought to play a key role as an effector cytokine in UC . Anrukinzumab , a humanised antibody that inhibits human IL-13 , was evaluated for the treatment of UC . Design In a multicentre , r and omised , double-blind , placebo-controlled study , patients with active UC ( Mayo score ≥4 and < 10 ) were r and omised to anrukinzumab 200 , 400 or 600 mg or placebo . Patients received five intravenous administrations over 14 weeks . The primary endpoint was fold change from baseline in faecal calprotectin ( FC ) at Week 14 . Secondary endpoints included safety , pharmacokinetics and IL-13 levels . Results The modified intention-to-treat population included 84 patients ( 21 patients /arm ) . Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo . The study had a high dropout rate , in part , related to lack of efficacy . The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score , clinical response , clinical remission and proportion of subjects with mucosal healing . An increase in serum total IL-13 ( free and bound to anrukinzumab ) was observed for all anrukinzumab groups but not with placebo . This suggests significant binding of anrukinzumab to IL-13 . The safety profile was not different between the anrukinzumab and placebo groups . Conclusions A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13 . Trial registration number Clinical Trials.gov number NCT01284062 Objective Interleukin-13 ( IL-13 ) has been implicated as a key driver of UC . This trial evaluates the efficacy and safety of tralokinumab , an IL-13-neutralising antibody , as add-on therapy in adults with moderate-to-severe UC despite st and ard treatments . Design Non-hospitalised adults with UC ( total Mayo score ≥6 ) were r and omised to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks for 12 weeks . The primary end point was the rate of clinical response at week 8 . Secondary efficacy end points included clinical remission and mucosal healing rates at week 8 and changes in total Mayo score , total modified Riley score , partial Mayo score and disease activity markers . Results Clinical response rate was 38 % ( 21/56 ) for tralokinumab vs 33 % ( 18/55 ) for placebo ( p=0.406 ) . Clinical remission rate was 18 % ( 10/56 ) vs 6 % ( 3/55 ) ( p=0.033 ) and mucosal healing rate was 32 % ( 18/56 ) vs 20 % ( 11/55 ) ( p=0.104 ) for tralokinumab vs placebo . Changes to week 8 in total Mayo score and total modified Riley score were similar for tralokinumab and placebo ( least-squares mean difference between groups : −0.49 ( p=0.394 ) and 0.25 ( p=0.449 ) , respectively ) . Partial Mayo score at week 4 was lower with tralokinumab than placebo ( least-squares mean difference between groups : −0.90 ( p=0.041 ) ) . No consistent patterns were observed for disease activity markers . Tralokinumab had an acceptable safety profile . Conclusions Add-on therapy with tralokinumab did not significantly improve clinical response . However , the higher clinical remission rate with tralokinumab than placebo suggests that tralokinumab may benefit some patients with UC .  Tralokinumab was well tolerated . Trial registration number Clinical Trials.gov number : NCT01482884 BACKGROUND In phase 2 trials , lebrikizumab , an anti-interleukin-13 monoclonal antibody , reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma , particularly in those with high concentrations of type 2 biomarkers ( eg , periostin or blood eosinophils ) . We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication . METHODS Adult patients with uncontrolled asthma , pre-bronchodilator FEV1 40 - 80 % predicted , and stable background therapy were r and omly assigned ( 1:1:1 ) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg , or placebo subcutaneously , once every 4 weeks . R and omisation was stratified by screening serum periostin concentration , history of asthma exacerbations within the last 12 months , baseline asthma medications , and country . The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients ( periostin ≥50 ng/mL or blood eosinophils ≥300 cells per μL ) , analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group , number of asthma exacerbations within the 12 months before study entry , baseline asthma medications , geographic region , screening periostin concentration , and blood eosinophil counts as covariates . Both trials are registered at Clinical Trials.gov , LAVOLTA I , number NCT01867125 , and LAVOLTA II , number NCT01868061 . FINDINGS 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II . Over 52 weeks , lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group ( rate ratio [ RR ] 0·49 [ 95 % CI 0·34 - 0·69 ] , p<0·0001 ) and in the 125 mg dose group ( RR 0·70 [ 0·51 - 0·95 ] , p=0·0232 ) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II ( 37·5 mg : RR 0·74 [ 95 % CI 0·54 - 1·01 ] , p=0·0609 ; 125 mg : RR 0·74 [ 0·54 - 1·02 ] , p=0·0626 ) . Pooling both studies , the proportion of patients who experienced treatment-emergent adverse events ( 79 % [ 1125 of 1432 patients ] for both lebrikizumab doses vs 80 % [ 576 of 716 patients ] for placebo ) , serious adverse events ( 8 % [ 115 patients ] for both lebrikizumab doses vs 9 % [ 65 patients ] for placebo ) , and adverse events leading to study drug discontinuation ( 3 % [ 49 patients ] for both lebrikizumab doses vs 4 % [ 31 patients ] for placebo ) were similar between lebrikizumab and placebo . The following serious adverse events were reported in the placebo-controlled period : one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group . INTERPRETATION Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients . However , it blocked interleukin-13 as evidence d by the effect on interleukin-13-related pharmacodynamic biomarkers , and clinical ly relevant changes could not be ruled out . FUNDING F Hoffmann-La Roche AIM To assess the bioavailability and pharmacokinetics of CAT-354 , an anti-IL-13 human monoclonal IgG4 antibody , following subcutaneous ( s.c . ) and intravenous ( i.v . ) administration . METHODS This was a single-dose , r and omized , open-label , parallel-group bioavailability study . Healthy male subjects aged 20 - 54 years were r and omly assigned to one of three dose groups ( n= 10/group ) to receive CAT-354 : 150 mg i.v . ; 150 mg s.c . or 300 mg s.c . ( two 150 mg injections ) . Serum pharmacokinetics , adverse events ( AEs ) , vital signs , electrocardiograms and laboratory parameters were assessed . RESULTS CAT-354 showed bioavailability of 62 % and 60 % after 150 mg and 300 mg s.c . doses , respectively , and linear pharmacokinetics over the dose range tested . Peak serum concentrations in the s.c . groups occurred after 3 - 9 ( median 5 ) days , with a mean elimination half-life of 19.2 + /- 3.1 days ( 150 mg ) and 19.4 + /- 3.59 days ( 300 mg ) after s.c . and 21.4 + /- 2.46 days after i.v . administration . Volume of distribution at steady state ( V(ss ) ) was 4960 + /- 1440 ml kg(-1 ) after i.v . ( slightly greater than plasma volume ) . Average apparent clearances ( CL/F ) were 292 + /- 82.3 and 307 + /- 109 ml day(-1 ) after 150 and 300 mg s.c . , respectively ; systemic CL of 188 + /- 84.0 ml day(-1 ) after i.v . dosing was consistent with endogenous IgG and reticuloendothelial elimination . No severe or serious AEs occurred . Among 40 reported AEs , 25 were headache , sinus disorders/respiratory symptoms and changes in body temperature perception . CONCLUSIONS CAT-354 exhibited bioavailability of approximately 60 % when given s.c . to healthy male subjects Background IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness . This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody ( CAT-354 ) in adults with asthma . Methods This was a multiple-dose , r and omised , double-blind , placebo-controlled phase 1 study in asthmatics ( 
    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 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 . ) Objective Interleukin 13 ( IL-13 ) is thought to play a key role as an effector cytokine in UC . Anrukinzumab , a humanised antibody that inhibits human IL-13 , was evaluated for the treatment of UC . Design In a multicentre , r and omised , double-blind , placebo-controlled study , patients with active UC ( Mayo score ≥4 and < 10 ) were r and omised to anrukinzumab 200 , 400 or 600 mg or placebo . Patients received five intravenous administrations over 14 weeks . The primary endpoint was fold change from baseline in faecal calprotectin ( FC ) at Week 14 . Secondary endpoints included safety , pharmacokinetics and IL-13 levels . Results The modified intention-to-treat population included 84 patients ( 21 patients /arm ) . Fold change of FC from baseline at Week 14 was not significantly different for any treatment groups compared with the placebo . The study had a high dropout rate , in part , related to lack of efficacy . The exploratory comparisons of each dose were not significantly different from placebo in terms of change from baseline in total Mayo score , clinical response , clinical remission and proportion of subjects with mucosal healing . An increase in serum total IL-13 ( free and bound to anrukinzumab ) was observed for all anrukinzumab groups but not with placebo . This suggests significant binding of anrukinzumab to IL-13 . The safety profile was not different between the anrukinzumab and placebo groups . Conclusions A statistically significant therapeutic effect of anrukinzumab could not be demonstrated in patients with active UC in spite of binding of anrukinzumab to IL-13 . Trial registration number Clinical Trials.gov number NCT01284062 Objective Interleukin-13 ( IL-13 ) has been implicated as a key driver of UC . This trial evaluates the efficacy and safety of tralokinumab , an IL-13-neutralising antibody , as add-on therapy in adults with moderate-to-severe UC despite st and ard treatments . Design Non-hospitalised adults with UC ( total Mayo score ≥6 ) were r and omised to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks for 12 weeks . The primary end point was the rate of clinical response at week 8 . Secondary efficacy end points included clinical remission and mucosal healing rates at week 8 and changes in total Mayo score , total modified Riley score , partial Mayo score and disease activity markers . Results Clinical response rate was 38 % ( 21/56 ) for tralokinumab vs 33 % ( 18/55 ) for placebo ( p=0.406 ) . Clinical remission rate was 18 % ( 10/56 ) vs 6 % ( 3/55 ) ( p=0.033 ) and mucosal healing rate was 32 % ( 18/56 ) vs 20 % ( 11/55 ) ( p=0.104 ) for tralokinumab vs placebo . Changes to week 8 in total Mayo score and total modified Riley score were similar for tralokinumab and placebo ( least-squares mean difference between groups : −0.49 ( p=0.394 ) and 0.25 ( p=0.449 ) , respectively ) . Partial Mayo score at week 4 was lower with tralokinumab than placebo ( least-squares mean difference between groups : −0.90 ( p=0.041 ) ) . No consistent patterns were observed for disease activity markers . Tralokinumab had an acceptable safety profile . Conclusions Add-on therapy with tralokinumab did not significantly improve clinical response . However , the higher clinical remission rate with tralokinumab than placebo suggests that tralokinumab may benefit some patients with UC .  Tralokinumab was well tolerated . Trial registration number Clinical Trials.gov number : NCT01482884 BACKGROUND In phase 2 trials , lebrikizumab , an anti-interleukin-13 monoclonal antibody , reduced exacerbation rates and improved FEV1 in patients with uncontrolled asthma , particularly in those with high concentrations of type 2 biomarkers ( eg , periostin or blood eosinophils ) . We undertook replicate phase 3 studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma despite inhaled corticosteroids and at least one second controller medication . METHODS Adult patients with uncontrolled asthma , pre-bronchodilator FEV1 40 - 80 % predicted , and stable background therapy were r and omly assigned ( 1:1:1 ) with an interactive voice-web-based response system to receive lebrikizumab 37·5 mg or 125 mg , or placebo subcutaneously , once every 4 weeks . R and omisation was stratified by screening serum periostin concentration , history of asthma exacerbations within the last 12 months , baseline asthma medications , and country . The primary efficacy endpoint was the rate of asthma exacerbations over 52 weeks in biomarker-high patients ( periostin ≥50 ng/mL or blood eosinophils ≥300 cells per μL ) , analysed with a Poisson regression model corrected for overdispersion with Pearson χ2 that included terms for treatment group , number of asthma exacerbations within the 12 months before study entry , baseline asthma medications , geographic region , screening periostin concentration , and blood eosinophil counts as covariates . Both trials are registered at Clinical Trials.gov , LAVOLTA I , number NCT01867125 , and LAVOLTA II , number NCT01868061 . FINDINGS 1081 patients were treated in LAVOLTA I and 1067 patients in LAVOLTA II . Over 52 weeks , lebrikizumab reduced exacerbation rates in biomarker-high patients in the 37·5 mg dose group ( rate ratio [ RR ] 0·49 [ 95 % CI 0·34 - 0·69 ] , p<0·0001 ) and in the 125 mg dose group ( RR 0·70 [ 0·51 - 0·95 ] , p=0·0232 ) versus placebo in LAVOLTA I. Exacerbation rates were also reduced in biomarker-high patients in both dose groups versus placebo in LAVOLTA II ( 37·5 mg : RR 0·74 [ 95 % CI 0·54 - 1·01 ] , p=0·0609 ; 125 mg : RR 0·74 [ 0·54 - 1·02 ] , p=0·0626 ) . Pooling both studies , the proportion of patients who experienced treatment-emergent adverse events ( 79 % [ 1125 of 1432 patients ] for both lebrikizumab doses vs 80 % [ 576 of 716 patients ] for placebo ) , serious adverse events ( 8 % [ 115 patients ] for both lebrikizumab doses vs 9 % [ 65 patients ] for placebo ) , and adverse events leading to study drug discontinuation ( 3 % [ 49 patients ] for both lebrikizumab doses vs 4 % [ 31 patients ] for placebo ) were similar between lebrikizumab and placebo . The following serious adverse events were reported in the placebo-controlled period : one event of aplastic anaemia and five serious adverse events related to raised concentrations of eosinophils in patients treated with lebrikizumab and one event of eosinophilic pneumonia in the placebo group . INTERPRETATION Lebrikizumab did not consistently show significant reduction in asthma exacerbations in biomarker-high patients . However , it blocked interleukin-13 as evidence d by the effect on interleukin-13-related pharmacodynamic biomarkers , and clinical ly relevant changes could not be ruled out . FUNDING F Hoffmann-La Roche AIM To assess the bioavailability and pharmacokinetics of CAT-354 , an anti-IL-13 human monoclonal IgG4 antibody , following subcutaneous ( s.c . ) and intravenous ( i.v . ) administration . METHODS This was a single-dose , r and omized , open-label , parallel-group bioavailability study . Healthy male subjects aged 20 - 54 years were r and omly assigned to one of three dose groups ( n= 10/group ) to receive CAT-354 : 150 mg i.v . ; 150 mg s.c . or 300 mg s.c . ( two 150 mg injections ) . Serum pharmacokinetics , adverse events ( AEs ) , vital signs , electrocardiograms and laboratory parameters were assessed . RESULTS CAT-354 showed bioavailability of 62 % and 60 % after 150 mg and 300 mg s.c . doses , respectively , and linear pharmacokinetics over the dose range tested . Peak serum concentrations in the s.c . groups occurred after 3 - 9 ( median 5 ) days , with a mean elimination half-life of 19.2 + /- 3.1 days ( 150 mg ) and 19.4 + /- 3.59 days ( 300 mg ) after s.c . and 21.4 + /- 2.46 days after i.v . administration . Volume of distribution at steady state ( V(ss ) ) was 4960 + /- 1440 ml kg(-1 ) after i.v . ( slightly greater than plasma volume ) . Average apparent clearances ( CL/F ) were 292 + /- 82.3 and 307 + /- 109 ml day(-1 ) after 150 and 300 mg s.c . , respectively ; systemic CL of 188 + /- 84.0 ml day(-1 ) after i.v . dosing was consistent with endogenous IgG and reticuloendothelial elimination . No severe or serious AEs occurred . Among 40 reported AEs , 25 were headache , sinus disorders/respiratory symptoms and changes in body temperature perception . CONCLUSIONS CAT-354 exhibited bioavailability of approximately 60 % when given s.c . to healthy male subjects Background IL-13 has been implicated in the development of airway inflammation and hyperresponsiveness . This study investigated the multiple-dose pharmacokinetics and safety profile of human anti-IL-13 antibody ( CAT-354 ) in adults with asthma . Methods This was a multiple-dose , r and omised , double-blind , placebo-controlled phase 1 study in asthmatics ( 
    Output:
    