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 and aims : To evaluate the safety , pharmacokinetics and clinical efficacy of the intercellular adhesion molecule‐1 antisense phosphorothioate oligonucleotide alicaforsen ( ISIS 2302 ) at 250–350 mg in Crohn 's disease BACKGROUND & AIMS Intercellular adhesion molecule 1 ( ICAM-1 ) plays an important role in the trafficking and activation of leukocytes and is up-regulated in inflamed mucosa in Crohn 's disease . ISIS 2302 is an antisense phosphorothioate oligodeoxynucleotide that inhibits ICAM-1 expression . The aim of this study was to obtain preliminary assessment of tolerability , pharmacology , and efficacy of ISIS 2302 in Crohn 's disease . METHODS Twenty patients with active , steroid-treated Crohn 's disease were r and omized ( 3:1 , ISIS 2302 to placebo ) to receive over 26 days 13 intravenous infusions of ISIS 2302 ( 0.5 , 1 , or 2 mg/kg ) or saline placebo in a double-blinded study . The patients were followed up for 6 months . RESULTS At the end of treatment . 47 % ( 7 of 15 ) of ISIS 2302-treated and 20 % ( 1 of 5 ) of the placebo-treated patients were in remission ( Crohn 's Disease Activity Index [ CDAI ] < 150 ) . At the end of month 6 , 5 of these 7 ISIS 2302-treated remitters were still in remission , and a 6th patient had a CDAI of 156 . Corticosteroid usage was significantly lower ( P = 0.0001 ) in the ISIS 2302-treated patients . These findings were corroborated by significant increases in beta7 and alpha d bearing CD3 + peripheral blood lymphocytes and by decreases in intestinal mucosal ICAM-1 expression during the treatment period . CONCLUSIONS ISIS 2302 seems to be a well-tolerated and promising therapy for steroid-treated Crohn 's disease BACKGROUND Natalizumab , a humanized monoclonal antibody against alpha4 integrin , inhibits leukocyte adhesion and migration into inflamed tissue . METHODS We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn 's disease . In the first trial , 905 patients were r and omly assigned to receive 300 mg of natalizumab or placebo at weeks 0 , 4 , and 8 . The primary outcome was response , defined by a decrease in the Crohn 's Disease Activity Index ( CDAI ) score of at least 70 points , at week 10 . In the second trial , 339 patients who had a response to natalizumab in the first trial were r and omly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56 . The primary outcome was a sustained response through week 36 . A secondary outcome in both trials was disease remission ( a CDAI score of less than 150 ) . RESULTS In the first trial , the natalizumab and placebo groups had similar rates of response ( 56 percent and 49 percent , respectively ; P=0.05 ) and remission ( 37 percent and 30 percent , respectively ; P=0.12 ) at 10 weeks . Continuing natalizumab in the second trial result ed in higher rates of sustained response ( 61 percent vs. 28 percent , P<0.001 ) and remission ( 44 percent vs. 26 percent , P=0.003 ) through week 36 than did switching to placebo . Serious adverse events occurred in 7 percent of each group in the first trial and in 10 percent of the placebo group and 8 percent of the natalizumab group in the second trial . In an open-label extension study , a patient treated with natalizumab  died from progressive multifocal leukoencephalopathy , associated with the JC virus , a human polyomavirus . CONCLUSIONS Induction therapy with natalizumab for Crohn 's disease result ed in small , nonsignificant improvements in response and remission rates . Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks . The benefit of natalizumab will need to be weighed against the risk of serious adverse events , including progressive multifocal leukoencephalopathy . ( Clinical Trials.gov numbers , NCT00032786 and NCT00032799 . OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy BACKGROUND & AIMS ISIS-2302 , an antisense oligonucleotide directed against intercellular adhesion molecule 1 , was effective in steroid refractory Crohn 's disease in a pilot trial . The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn 's disease ( CACD ) . METHODS A dose-interval , multicenter , placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD ( Crohn 's Disease Activity Index [ CDAI ] , 200 - 400 ) . The primary endpoint was steroid-free remission ( CDAI < 150 ) at week 14 . RESULTS Only 2 of 60 ( 3.3 % ) ISIS-2302-treated and no placebo patients reached the primary endpoint . Steroid-free remission at week 26 ( secondary endpoint ) was reached in 8 of 60 ( 13.3 % ) active treatment and 1 of 15 ( 6.7 % ) placebo patients . A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose < 10 mg/day at weeks 14 and 26 ( 48.3 % vs. 33.3 % and 55.0 % vs. 40.0 % , respectively , and a glucocorticoid dose of 0 mg [ prednisone equivalent ] at week 26 [ 23.3 % vs. 6.7 % , respectively ] ) . Treatment with  ISIS-2302  was safe . The most common side effects were injection site reactions in the active treatment group ( 23 % in ISIS-2302-treated patients vs. none in placebo patients ) . No statistically significant differences in the frequency of side effects were detected between dose groups . CONCLUSIONS The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint . Positive trends were observed in some of the secondary endpoints BACKGROUND & AIMS Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease . This r and omized , double-blind , controlled trial assessed the efficacy and safety of MLN0002 , a monoclonal antibody targeting the alpha4beta7 integrin , in patients with active Crohn 's disease . METHODS Patients were r and omized to receive MLN0002 2.0 mg/kg ( n = 65 ) , MLN0002 0.5 mg/kg ( n = 62 ) , or placebo ( n = 58 ) by intravenous infusion on days 1 and 29 . The primary efficacy end point was clinical response ( > or=70-point decrement in the Crohn 's Disease Activity Index [ CDAI ] score ) on day 57 . Secondary end points were the proportions of patients with clinical remission ( CDAI score < or=150 ) and with an enhanced clinical response ( > or=100-point decrement in CDAI ) . Human anti-human antibody levels were measured . RESULTS Clinical response rates at day 57 were 53 % , 49 % , and 41 % in the MLN0002 2.0 mg/kg , MLN0002 0.5 mg/kg , and placebo groups . Clinical remission rates at day 57 were 37 % , 30 % , and 21 % , respectively ( P = .04 for the 2.0 mg/kg vs placebo comparison ) . At day 57 , 12 % and 34 % of patients in the 2.0- and 0.5-mg/kg groups had clinical ly significant human anti-human antibody levels ( titers > 1:125 ) . There was one infusion-related hypersensitivity reaction . The most common serious adverse event was worsening of Crohn 's disease . CONCLUSIONS This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission .  MLN0002 was well tolerated in patients with active Crohn 's disease Background : Natalizumab , a humanized monoclonal IgG4 antibody to & agr;4 integrin , was investigated as a treatment of active Crohn 's disease ( CD ) . The safety of natalizumab given in combination with infliximab has not previously been studied . Methods : Seventy‐nine adult patients with active CD ( Crohn 's Disease Activity Index [ CDAI ] score ≥ 150 ) despite ongoing infliximab treatment were r and omized 2:1 to receive 3 intravenous infusions of natalizumab  ( 300 mg ; n = 52 ) or placebo  ( n = 27 ) every 4 weeks . Patients received infliximab ( 5 mg/kg ) every 8 weeks for at least 10 weeks before r and omization and throughout the study . The primary objective was to assess the short‐term safety and tolerability  of natalizumab in patients concurrently receiving infliximab . Secondary and tertiary objectives included measures of efficacy , health‐related quality of life ( HRQoL ) , and effects on inflammatory markers . A subset of patients also participated in a pharmacokinetic/pharmacodynamic ( PK/PD ) analysis of the effects of concurrent treatment . Results : Incidence of adverse events ( AEs ) was similar in the treatment groups . AEs frequently reported in both groups were headache , CD exacerbation , nausea , and nasopharyngitis . No patient had a hypersensitivity‐like reaction to natalizumab , whereas 4 patients ( 5 % ) experienced reactions to infliximab . Two patients ( 4 % ) developed anti‐natalizumab antibodies ; 10 patients ( 14 % ) developed anti‐infliximab antibodies . The mean CDAI score  decreased with natalizumab plus infliximab but was unchanged with infliximab alone ( −37.7 versus + 3.5 ; P = 0.084 ) . Patients in both groups showed small increases in HRQoL ( P = 0.811 ) . No drug – drug interactions were noted . Conclusions : The combination of natalizumab plus infliximab was well tolerated . Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone Serological profiles for anti‐Saccharomyces cerevisiae antibodies (ASCA)/ perinuclear antineutrophil cytoplasmic antibodies ( pANCA ) and gene polymorphisms in tumour necrosis factor (TNF)‐α and intercellular adhesion molecule‐1 ( ICAM‐1 ) are associated with occurrence and /or outcome in Crohn 's disease . The aim of the study was to 
    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 and aims : To evaluate the safety , pharmacokinetics and clinical efficacy of the intercellular adhesion molecule‐1 antisense phosphorothioate oligonucleotide alicaforsen ( ISIS 2302 ) at 250–350 mg in Crohn 's disease BACKGROUND & AIMS Intercellular adhesion molecule 1 ( ICAM-1 ) plays an important role in the trafficking and activation of leukocytes and is up-regulated in inflamed mucosa in Crohn 's disease . ISIS 2302 is an antisense phosphorothioate oligodeoxynucleotide that inhibits ICAM-1 expression . The aim of this study was to obtain preliminary assessment of tolerability , pharmacology , and efficacy of ISIS 2302 in Crohn 's disease . METHODS Twenty patients with active , steroid-treated Crohn 's disease were r and omized ( 3:1 , ISIS 2302 to placebo ) to receive over 26 days 13 intravenous infusions of ISIS 2302 ( 0.5 , 1 , or 2 mg/kg ) or saline placebo in a double-blinded study . The patients were followed up for 6 months . RESULTS At the end of treatment . 47 % ( 7 of 15 ) of ISIS 2302-treated and 20 % ( 1 of 5 ) of the placebo-treated patients were in remission ( Crohn 's Disease Activity Index [ CDAI ] < 150 ) . At the end of month 6 , 5 of these 7 ISIS 2302-treated remitters were still in remission , and a 6th patient had a CDAI of 156 . Corticosteroid usage was significantly lower ( P = 0.0001 ) in the ISIS 2302-treated patients . These findings were corroborated by significant increases in beta7 and alpha d bearing CD3 + peripheral blood lymphocytes and by decreases in intestinal mucosal ICAM-1 expression during the treatment period . CONCLUSIONS ISIS 2302 seems to be a well-tolerated and promising therapy for steroid-treated Crohn 's disease BACKGROUND Natalizumab , a humanized monoclonal antibody against alpha4 integrin , inhibits leukocyte adhesion and migration into inflamed tissue . METHODS We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn 's disease . In the first trial , 905 patients were r and omly assigned to receive 300 mg of natalizumab or placebo at weeks 0 , 4 , and 8 . The primary outcome was response , defined by a decrease in the Crohn 's Disease Activity Index ( CDAI ) score of at least 70 points , at week 10 . In the second trial , 339 patients who had a response to natalizumab in the first trial were r and omly reassigned to receive 300 mg of natalizumab or placebo every four weeks through week 56 . The primary outcome was a sustained response through week 36 . A secondary outcome in both trials was disease remission ( a CDAI score of less than 150 ) . RESULTS In the first trial , the natalizumab and placebo groups had similar rates of response ( 56 percent and 49 percent , respectively ; P=0.05 ) and remission ( 37 percent and 30 percent , respectively ; P=0.12 ) at 10 weeks . Continuing natalizumab in the second trial result ed in higher rates of sustained response ( 61 percent vs. 28 percent , P<0.001 ) and remission ( 44 percent vs. 26 percent , P=0.003 ) through week 36 than did switching to placebo . Serious adverse events occurred in 7 percent of each group in the first trial and in 10 percent of the placebo group and 8 percent of the natalizumab group in the second trial . In an open-label extension study , a patient treated with natalizumab  died from progressive multifocal leukoencephalopathy , associated with the JC virus , a human polyomavirus . CONCLUSIONS Induction therapy with natalizumab for Crohn 's disease result ed in small , nonsignificant improvements in response and remission rates . Patients who had a response had significantly increased rates of sustained response and remission if natalizumab was continued every four weeks . The benefit of natalizumab will need to be weighed against the risk of serious adverse events , including progressive multifocal leukoencephalopathy . ( Clinical Trials.gov numbers , NCT00032786 and NCT00032799 . OBJECTIVES : We evaluated the effects of treatment on health-related quality of life ( HRQoL ) during a r and omized controlled trial of natalizumab maintenance therapy ( ENACT-2 ) using both disease-specific and generic measures . METHODS : Crohn 's disease patients who received natalizumab as induction therapy in ENACT-1 ( N = 724 ) and responded ( N = 339 ) were re-r and omized to ENACT-2 in which they received natalizumab 300 mg ( N = 168 ) or placebo ( N = 171 ) every 4 wk for 48 additional wk . Outcome measures were the change from baseline on the inflammatory bowel disease question naire ( IBDQ ) , the short form-36 ( SF-36 ) , the EuroQol-5D ( EQ-5D ) , and a subject global assessment . RESULTS : At entry into ENACT-1 , scores indicated substantially impaired HRQoL for both the disease-specific and general measures . Natalizumab responders showed clinical ly meaningful improvement in HRQoL over the course of the ENACT-1 study . During maintenance therapy , IBDQ and SF-36 scale scores of patients who responded to natalizumab induction and were re-r and omized to receive the drug in ENACT-2 ( N = 168 ) remained stable , while those re-r and omized to placebo ( N = 171 ) worsened . At week 60 , 48 wk after the initiation of maintenance therapy , the mean change from ENACT-1 baseline of all scales of the IBDQ and the SF-36 was significantly higher for those who continued to receive natalizumab ( P < 0.001 for all scales ) . The scores of patients who received maintenance natalizumab treatment were not statistically different from those of a cross-section of the U.S. population for 6 of 8 scales of the SF-36 . CONCLUSIONS : The substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 wk of maintenance therapy BACKGROUND & AIMS ISIS-2302 , an antisense oligonucleotide directed against intercellular adhesion molecule 1 , was effective in steroid refractory Crohn 's disease in a pilot trial . The aim of this study was to investigate safety and efficacy of ISIS-2302 in chronic active Crohn 's disease ( CACD ) . METHODS A dose-interval , multicenter , placebo-controlled trial was conducted in 75 patients with steroid-refractory CACD ( Crohn 's Disease Activity Index [ CDAI ] , 200 - 400 ) . The primary endpoint was steroid-free remission ( CDAI < 150 ) at week 14 . RESULTS Only 2 of 60 ( 3.3 % ) ISIS-2302-treated and no placebo patients reached the primary endpoint . Steroid-free remission at week 26 ( secondary endpoint ) was reached in 8 of 60 ( 13.3 % ) active treatment and 1 of 15 ( 6.7 % ) placebo patients . A greater proportion of ISIS-2302-treated than placebo patients achieved a steroid dose < 10 mg/day at weeks 14 and 26 ( 48.3 % vs. 33.3 % and 55.0 % vs. 40.0 % , respectively , and a glucocorticoid dose of 0 mg [ prednisone equivalent ] at week 26 [ 23.3 % vs. 6.7 % , respectively ] ) . Treatment with  ISIS-2302  was safe . The most common side effects were injection site reactions in the active treatment group ( 23 % in ISIS-2302-treated patients vs. none in placebo patients ) . No statistically significant differences in the frequency of side effects were detected between dose groups . CONCLUSIONS The trial did not prove clinical efficacy of ISIS-2302 based on the primary endpoint . Positive trends were observed in some of the secondary endpoints BACKGROUND & AIMS Selective blockade of lymphocyte-vascular endothelium interactions in the gastrointestinal tract is a promising therapeutic strategy for inflammatory bowel disease . This r and omized , double-blind , controlled trial assessed the efficacy and safety of MLN0002 , a monoclonal antibody targeting the alpha4beta7 integrin , in patients with active Crohn 's disease . METHODS Patients were r and omized to receive MLN0002 2.0 mg/kg ( n = 65 ) , MLN0002 0.5 mg/kg ( n = 62 ) , or placebo ( n = 58 ) by intravenous infusion on days 1 and 29 . The primary efficacy end point was clinical response ( > or=70-point decrement in the Crohn 's Disease Activity Index [ CDAI ] score ) on day 57 . Secondary end points were the proportions of patients with clinical remission ( CDAI score < or=150 ) and with an enhanced clinical response ( > or=100-point decrement in CDAI ) . Human anti-human antibody levels were measured . RESULTS Clinical response rates at day 57 were 53 % , 49 % , and 41 % in the MLN0002 2.0 mg/kg , MLN0002 0.5 mg/kg , and placebo groups . Clinical remission rates at day 57 were 37 % , 30 % , and 21 % , respectively ( P = .04 for the 2.0 mg/kg vs placebo comparison ) . At day 57 , 12 % and 34 % of patients in the 2.0- and 0.5-mg/kg groups had clinical ly significant human anti-human antibody levels ( titers > 1:125 ) . There was one infusion-related hypersensitivity reaction . The most common serious adverse event was worsening of Crohn 's disease . CONCLUSIONS This phase 2 study was suggestive of a dose-dependent beneficial effect of MLN0002 therapy on clinical remission .  MLN0002 was well tolerated in patients with active Crohn 's disease Background : Natalizumab , a humanized monoclonal IgG4 antibody to & agr;4 integrin , was investigated as a treatment of active Crohn 's disease ( CD ) . The safety of natalizumab given in combination with infliximab has not previously been studied . Methods : Seventy‐nine adult patients with active CD ( Crohn 's Disease Activity Index [ CDAI ] score ≥ 150 ) despite ongoing infliximab treatment were r and omized 2:1 to receive 3 intravenous infusions of natalizumab  ( 300 mg ; n = 52 ) or placebo  ( n = 27 ) every 4 weeks . Patients received infliximab ( 5 mg/kg ) every 8 weeks for at least 10 weeks before r and omization and throughout the study . The primary objective was to assess the short‐term safety and tolerability  of natalizumab in patients concurrently receiving infliximab . Secondary and tertiary objectives included measures of efficacy , health‐related quality of life ( HRQoL ) , and effects on inflammatory markers . A subset of patients also participated in a pharmacokinetic/pharmacodynamic ( PK/PD ) analysis of the effects of concurrent treatment . Results : Incidence of adverse events ( AEs ) was similar in the treatment groups . AEs frequently reported in both groups were headache , CD exacerbation , nausea , and nasopharyngitis . No patient had a hypersensitivity‐like reaction to natalizumab , whereas 4 patients ( 5 % ) experienced reactions to infliximab . Two patients ( 4 % ) developed anti‐natalizumab antibodies ; 10 patients ( 14 % ) developed anti‐infliximab antibodies . The mean CDAI score  decreased with natalizumab plus infliximab but was unchanged with infliximab alone ( −37.7 versus + 3.5 ; P = 0.084 ) . Patients in both groups showed small increases in HRQoL ( P = 0.811 ) . No drug – drug interactions were noted . Conclusions : The combination of natalizumab plus infliximab was well tolerated . Several positive trends suggested that treating patients not in remission with infliximab plus natalizumab had greater efficacy than treatment with infliximab alone Serological profiles for anti‐Saccharomyces cerevisiae antibodies (ASCA)/ perinuclear antineutrophil cytoplasmic antibodies ( pANCA ) and gene polymorphisms in tumour necrosis factor (TNF)‐α and intercellular adhesion molecule‐1 ( ICAM‐1 ) are associated with occurrence and /or outcome in Crohn 's disease . The aim of the study was to 
    Output:
    