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 : Vedolizumab is a gut-selective & agr;4&bgr;7 integrin antagonist for the treatment of moderately to severely active Crohn 's disease ( CD ) . Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha ( TNF-&agr ; ) antagonist therapy ( TNF-naïve ) or who had discontinued TNF-&agr ; antagonist therapy because of inadequate response ( i.e. , primary nonresponse ) , loss of response , or intolerance ( collectively classified as the TNF-failure population ) . Methods : Post hoc analyses of the efficacy data for 516 TNF-naïve and 960 TNF-failure patients from the GEMINI 2 and GEMINI 3 trials were evaluated at weeks 6 , 10 , and 52 and included clinical remission ( CD Activity Index [ CDAI ] score ⩽150 ) , enhanced clinical response ( ≥100-point decrease from baseline in CDAI score ) , durable clinical remission ( remission at ≥80 % of visits ) , and corticosteroid-free remission . Adverse events were summarized for the TNF-naïve and TNF-failure subgroups by treatment received . Results : Among patients who responded to vedolizumab induction at week 6 , 48.9 % of TNF-naïve and 27.7 % of TNF-failure patients were in remission  with vedolizumab at week 52 ( versus 26.8 % and 12.8 % with  placebo ) . Clinical efficacy was similar between the different types of TNF-&agr ; antagonist failure or the number of prior TNF-&agr ; antagonists failed . Safety profiles were similar in both sub population s. Conclusions : Vedolizumab had increased efficacy  over placebo in CD patients irrespective of TNF-&agr ; antagonist treatment history . Overall , rates of response and remission were numerically higher in patients  receiving vedolizumab  as a first biologic than in patients who had experienced TNF failure Background and Aims A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [ UC ] or Crohn 's disease [ CD ] has been reported . Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data . Methods Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated . Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [ Caverage ] as exposure measure . Results Higher vedolizumab concentrations were associated with higher clinical remission rates ; the exposure-efficacy relationship was steeper for UC than CD . Unadjusted analyses overestimated the relationship , more so for CD . From covariate-adjusted models , average probability of remission at Week 6 increased by approximately 15 % for UC and 10 % for CD between Caverage values of 35 and 84 µg/ml [ 5th and 95th percentiles , respectively ] . On average , patients with higher albumin , lower faecal calprotectin [ UC only ] , lower C-reactive protein [ CD only ] , and no previous tumour necrosis factor-α [ TNFα ] antagonist use had a higher remission probability . Previous TNFα antagonist use had the greatest impact ; remission probability was approximately 10 % higher in treatment-naïve patients . Conclusions Higher vedolizumab  serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD . This relationship is affected by several factors , including previous TNFα antagonist use . Prospect i ve studies are needed to assess vedolizumab dose individualisation and optimisation BACKGROUND Ozanimod ( RPC1063 ) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration , potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract . METHODS We conducted a double-blind , placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis . Patients were r and omly assigned , in a 1:1:1 ratio , to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks . The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12 , with higher scores indicating more severe disease ; subscores range from 0 to 3 , with higher scores indicating more severe disease . The primary outcome was clinical remission ( Mayo Clinic score ≤2 , with no subscore > 1 ) at 8 weeks . RESULTS The primary outcome occurred in 16 % of the patients who received 1 mg of ozanimod and in 14 % of those who received 0.5 mg of ozanimod , as compared with 6 % of those who received placebo ( P=0.048 and P=0.14 , respectively , for the comparison of the two doses of ozanimod with placebo ) . Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant ; therefore , the hierarchical testing plan deemed the analyses of secondary outcomes exploratory . Clinical response ( decrease in Mayo Clinic score of ≥3 points and ≥30 % and decrease in rectal-bleeding subscore of ≥1 point or a subscore ≤1 ) at 8 weeks occurred in 57 % of those receiving 1 mg of ozanimod and 54 % of those receiving 0.5 mg , as compared with 37 % of those receiving placebo . At week 32 , the rate of clinical remission was 21 % in the group that received 1 mg of ozanimod , 26 % in the group that received 0.5 mg of ozanimod , and 6 % in the group that received placebo ; the rate of clinical response was 51 % , 35 % , and 20 % , respectively . At week 8 , absolute lymphocyte counts declined 49 % from baseline in the group that received 1 mg of ozanimod and 32 % from baseline in the group that received 0.5 mg . The most common adverse events overall were anemia and headache . CONCLUSIONS In this preliminary trial , ozanimod at a daily dose of 1 mg result ed in a slightly higher rate of clinical remission of ulcerative colitis than placebo . The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety . ( Funded by Receptos ; TOUCHSTONE Clinical Trials.gov number , NCT01647516 . ) BACKGROUND Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of the heterodimeric integrins α4β7 and αEβ7 . We aim ed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis . METHODS In this double-blind , placebo-controlled , r and omised , phase 2 study , patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries . Eligible patients ( aged 18 - 75 years ; Mayo Clinic Score [ MCS ] of 5 of higher [ or ≥6 in USA ] ; and disease extending 25 cm or more from anal verge ) were r and omised ( 1:1:1 ) to one of two dose levels of subcutaneous etrolizumab  ( 100 mg at weeks 0 , 4 , and 8 , with placebo at week 2 ; or 420 mg loading dose [ LD ] at week 0 followed by 300 mg at weeks 2 , 4 , and 8) , or matching placebo . The primary endpoint was clinical remission at week 10 , defined as MCS of 2 or less ( with no individual subscore of > 1 ) , analysed in the modified intention-to-treat population ( mITT ; all r and omly assigned patients who had received at least one dose of study drug , had at least one post-baseline disease-activity assessment , and had a central ly read screening endoscopic subscore of ≥2 ) . This study is registered with Clinical Trials.gov , number NCT01336465 . FINDINGS Between Sept 2 , 2011 , and July 11 , 2012 , 124 patients were r and omly assigned , of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population , leaving 39 patients in the etrolizumab 100 mg group , 39 in the etrolizumab 300 mg plus LD group , and 41 in the placebo group for the primary analyses . No patients in the placebo group had clinical remission at week 10 , compared with eight ( 21 % [ 95 % CI 7 - 36 ] ) patients in the etrolizumab 100 mg group ( p=0·0040 ) and four ( 10 % [ 0·2 - 24 ] ) patients in the 300 mg plus LD group ( p=0·048 ) . Adverse events occurred in 25 ( 61 % ) of 41 patients in the etrolizumab 100 mg group ( five [ 12 % ] of which were regarded as serious ) , 19 ( 48 % ) of 40 patients in the etrolizumab 300 mg plus LD group ( two [ 5 % ] serious ) , and 31 ( 72 % ) of 43 patients in the placebo group ( five [ 12 % ] serious ) . INTERPRETATION Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo . Therefore , blockade of both α4β7 and αEβ7 might provide a unique therapeutic approach for the treatment of ulcerative colitis , and phase 3 studies have been planned . FUNDING Genentech BACKGROUND Ustekinumab , a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 , was evaluated as an intravenous induction therapy in two population s with moderately to severely active Crohn 's disease .  Ustekinumab was also evaluated as subcutaneous maintenance therapy . METHODS We r and omly assigned patients to receive a single intravenous dose of ustekinumab ( either 130 mg or approximately 6 mg per kilogram of body weight ) or placebo in two induction trials . The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor ( TNF ) antagonists or had unacceptable side effects . The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred . Patients who completed these induction trials then participated in IM-UNITI , in which the 397 patients who had a response to ustekinumab  were r and omly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab ( either every 8 weeks or every 12 weeks ) or placebo . The primary end point for the induction trials was a clinical response at week 6 ( defined as a decrease from baseline in the Crohn 's Disease Activity Index [ CDAI ] score of ≥100 points or a CDAI score < 150 ) . The primary end point for the maintenance trial was remission at week 44 ( CDAI score < 150 ) . RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo ( in UNITI-1 , 34.3 % , 33.7 % , and 21.5 % , respectively , with P≤0.003 for both comparisons with placebo ; in UNITI-2 , 51.7 % , 55.5 % , and 28.7 % , respectively , with P<0.001 for both doses ) . In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks , 53.1 % and 48.8 % , respectively , were in remission at week 44 , as compared with 35.9 % of those receiving placebo ( P=0.005 and P=0.04 , respectively ) . Within each trial , adverse-event rates were similar among treatment groups . CONCLUSIONS Among patients with moderately to severely active Crohn 's disease , those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo . Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy . ( Funded by Janssen Research and Development ; Clinical Trials.gov numbers , NCT01369329 , NCT01369342 , and NCT01369355 . ) BACKGROUND The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn 's disease . We aim ed to assess the efficacy and safety of risankizumab ( BI 655066 , Boehringer Ingelheim , Ingelheim , Germany ) , a humanised 
    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 : Vedolizumab is a gut-selective & agr;4&bgr;7 integrin antagonist for the treatment of moderately to severely active Crohn 's disease ( CD ) . Aims of this study were to characterize the efficacy and safety of vedolizumab induction and maintenance therapy in patients who were naïve to tumor necrosis factor-alpha ( TNF-&agr ; ) antagonist therapy ( TNF-naïve ) or who had discontinued TNF-&agr ; antagonist therapy because of inadequate response ( i.e. , primary nonresponse ) , loss of response , or intolerance ( collectively classified as the TNF-failure population ) . Methods : Post hoc analyses of the efficacy data for 516 TNF-naïve and 960 TNF-failure patients from the GEMINI 2 and GEMINI 3 trials were evaluated at weeks 6 , 10 , and 52 and included clinical remission ( CD Activity Index [ CDAI ] score ⩽150 ) , enhanced clinical response ( ≥100-point decrease from baseline in CDAI score ) , durable clinical remission ( remission at ≥80 % of visits ) , and corticosteroid-free remission . Adverse events were summarized for the TNF-naïve and TNF-failure subgroups by treatment received . Results : Among patients who responded to vedolizumab induction at week 6 , 48.9 % of TNF-naïve and 27.7 % of TNF-failure patients were in remission  with vedolizumab at week 52 ( versus 26.8 % and 12.8 % with  placebo ) . Clinical efficacy was similar between the different types of TNF-&agr ; antagonist failure or the number of prior TNF-&agr ; antagonists failed . Safety profiles were similar in both sub population s. Conclusions : Vedolizumab had increased efficacy  over placebo in CD patients irrespective of TNF-&agr ; antagonist treatment history . Overall , rates of response and remission were numerically higher in patients  receiving vedolizumab  as a first biologic than in patients who had experienced TNF failure Background and Aims A positive relationship between vedolizumab trough serum concentrations and clinical outcomes in patients with ulcerative colitis [ UC ] or Crohn 's disease [ CD ] has been reported . Here we further explore exposure-efficacy relationships for vedolizumab induction therapy in post hoc analyses of GEMINI study data . Methods Vedolizumab trough concentrations at Week 6 or 10 were grouped in quartiles and clinical outcome rates calculated . Exposure-efficacy relationships at Week 6 and potential baseline covariate effects were explored using logistic regression and individual predicted cumulative average concentration through Week 6 [ Caverage ] as exposure measure . Results Higher vedolizumab concentrations were associated with higher clinical remission rates ; the exposure-efficacy relationship was steeper for UC than CD . Unadjusted analyses overestimated the relationship , more so for CD . From covariate-adjusted models , average probability of remission at Week 6 increased by approximately 15 % for UC and 10 % for CD between Caverage values of 35 and 84 µg/ml [ 5th and 95th percentiles , respectively ] . On average , patients with higher albumin , lower faecal calprotectin [ UC only ] , lower C-reactive protein [ CD only ] , and no previous tumour necrosis factor-α [ TNFα ] antagonist use had a higher remission probability . Previous TNFα antagonist use had the greatest impact ; remission probability was approximately 10 % higher in treatment-naïve patients . Conclusions Higher vedolizumab  serum concentrations were associated with higher remission rates after induction therapy in patients with moderately to severely active UC or CD . This relationship is affected by several factors , including previous TNFα antagonist use . Prospect i ve studies are needed to assess vedolizumab dose individualisation and optimisation BACKGROUND Ozanimod ( RPC1063 ) is an oral agonist of the sphingosine-1-phosphate receptor subtypes 1 and 5 that induces peripheral lymphocyte sequestration , potentially decreasing the number of activated lymphocytes circulating to the gastrointestinal tract . METHODS We conducted a double-blind , placebo-controlled phase 2 trial of ozanimod in 197 adults with moderate-to-severe ulcerative colitis . Patients were r and omly assigned , in a 1:1:1 ratio , to receive ozanimod at a dose of 0.5 mg or 1 mg or placebo daily for up to 32 weeks . The Mayo Clinic score was used to measure disease activity on a scale from 0 to 12 , with higher scores indicating more severe disease ; subscores range from 0 to 3 , with higher scores indicating more severe disease . The primary outcome was clinical remission ( Mayo Clinic score ≤2 , with no subscore > 1 ) at 8 weeks . RESULTS The primary outcome occurred in 16 % of the patients who received 1 mg of ozanimod and in 14 % of those who received 0.5 mg of ozanimod , as compared with 6 % of those who received placebo ( P=0.048 and P=0.14 , respectively , for the comparison of the two doses of ozanimod with placebo ) . Differences in the primary outcome between the group that received 0.5 mg of ozanimod and the placebo group were not significant ; therefore , the hierarchical testing plan deemed the analyses of secondary outcomes exploratory . Clinical response ( decrease in Mayo Clinic score of ≥3 points and ≥30 % and decrease in rectal-bleeding subscore of ≥1 point or a subscore ≤1 ) at 8 weeks occurred in 57 % of those receiving 1 mg of ozanimod and 54 % of those receiving 0.5 mg , as compared with 37 % of those receiving placebo . At week 32 , the rate of clinical remission was 21 % in the group that received 1 mg of ozanimod , 26 % in the group that received 0.5 mg of ozanimod , and 6 % in the group that received placebo ; the rate of clinical response was 51 % , 35 % , and 20 % , respectively . At week 8 , absolute lymphocyte counts declined 49 % from baseline in the group that received 1 mg of ozanimod and 32 % from baseline in the group that received 0.5 mg . The most common adverse events overall were anemia and headache . CONCLUSIONS In this preliminary trial , ozanimod at a daily dose of 1 mg result ed in a slightly higher rate of clinical remission of ulcerative colitis than placebo . The trial was not large enough or of sufficiently long duration to establish clinical efficacy or assess safety . ( Funded by Receptos ; TOUCHSTONE Clinical Trials.gov number , NCT01647516 . ) BACKGROUND Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of the heterodimeric integrins α4β7 and αEβ7 . We aim ed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis . METHODS In this double-blind , placebo-controlled , r and omised , phase 2 study , patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries . Eligible patients ( aged 18 - 75 years ; Mayo Clinic Score [ MCS ] of 5 of higher [ or ≥6 in USA ] ; and disease extending 25 cm or more from anal verge ) were r and omised ( 1:1:1 ) to one of two dose levels of subcutaneous etrolizumab  ( 100 mg at weeks 0 , 4 , and 8 , with placebo at week 2 ; or 420 mg loading dose [ LD ] at week 0 followed by 300 mg at weeks 2 , 4 , and 8) , or matching placebo . The primary endpoint was clinical remission at week 10 , defined as MCS of 2 or less ( with no individual subscore of > 1 ) , analysed in the modified intention-to-treat population ( mITT ; all r and omly assigned patients who had received at least one dose of study drug , had at least one post-baseline disease-activity assessment , and had a central ly read screening endoscopic subscore of ≥2 ) . This study is registered with Clinical Trials.gov , number NCT01336465 . FINDINGS Between Sept 2 , 2011 , and July 11 , 2012 , 124 patients were r and omly assigned , of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population , leaving 39 patients in the etrolizumab 100 mg group , 39 in the etrolizumab 300 mg plus LD group , and 41 in the placebo group for the primary analyses . No patients in the placebo group had clinical remission at week 10 , compared with eight ( 21 % [ 95 % CI 7 - 36 ] ) patients in the etrolizumab 100 mg group ( p=0·0040 ) and four ( 10 % [ 0·2 - 24 ] ) patients in the 300 mg plus LD group ( p=0·048 ) . Adverse events occurred in 25 ( 61 % ) of 41 patients in the etrolizumab 100 mg group ( five [ 12 % ] of which were regarded as serious ) , 19 ( 48 % ) of 40 patients in the etrolizumab 300 mg plus LD group ( two [ 5 % ] serious ) , and 31 ( 72 % ) of 43 patients in the placebo group ( five [ 12 % ] serious ) . INTERPRETATION Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo . Therefore , blockade of both α4β7 and αEβ7 might provide a unique therapeutic approach for the treatment of ulcerative colitis , and phase 3 studies have been planned . FUNDING Genentech BACKGROUND Ustekinumab , a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23 , was evaluated as an intravenous induction therapy in two population s with moderately to severely active Crohn 's disease .  Ustekinumab was also evaluated as subcutaneous maintenance therapy . METHODS We r and omly assigned patients to receive a single intravenous dose of ustekinumab ( either 130 mg or approximately 6 mg per kilogram of body weight ) or placebo in two induction trials . The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor ( TNF ) antagonists or had unacceptable side effects . The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred . Patients who completed these induction trials then participated in IM-UNITI , in which the 397 patients who had a response to ustekinumab  were r and omly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab ( either every 8 weeks or every 12 weeks ) or placebo . The primary end point for the induction trials was a clinical response at week 6 ( defined as a decrease from baseline in the Crohn 's Disease Activity Index [ CDAI ] score of ≥100 points or a CDAI score < 150 ) . The primary end point for the maintenance trial was remission at week 44 ( CDAI score < 150 ) . RESULTS The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher than the rates among patients receiving placebo ( in UNITI-1 , 34.3 % , 33.7 % , and 21.5 % , respectively , with P≤0.003 for both comparisons with placebo ; in UNITI-2 , 51.7 % , 55.5 % , and 28.7 % , respectively , with P<0.001 for both doses ) . In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks , 53.1 % and 48.8 % , respectively , were in remission at week 44 , as compared with 35.9 % of those receiving placebo ( P=0.005 and P=0.04 , respectively ) . Within each trial , adverse-event rates were similar among treatment groups . CONCLUSIONS Among patients with moderately to severely active Crohn 's disease , those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo . Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy . ( Funded by Janssen Research and Development ; Clinical Trials.gov numbers , NCT01369329 , NCT01369342 , and NCT01369355 . ) BACKGROUND The interleukin-23 pathway is implicated genetically and biologically in the pathogenesis of Crohn 's disease . We aim ed to assess the efficacy and safety of risankizumab ( BI 655066 , Boehringer Ingelheim , Ingelheim , Germany ) , a humanised 
    Output:
    