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 : We assessed the tolerability and clinical benefit of adalimumab , a human antibody to tumor necrosis factor ( TNF ) , in patients with Crohn 's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab , but who no longer had a sustained response and /or tolerance to infliximab . METHODS : A total of 24 patients with Crohn 's disease who had lost responsiveness or developed intolerance ( acute or delayed infusion reactions ) to infliximab  were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2 . After week 4 , the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission , complete fistula closure , and complete steroid withdrawal . Outcome measures included the ability to tolerate adalimumab and clinical remission ( defined as a Crohn 's disease activity index ( CDAI ) score ≤150 points ) and clinical response ( defined as a decrease in the CDAI ) ≥100 points ) in patients who had a baseline CDAI score ≥220 . RESULTS : None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab ( including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab ) . Of 17 patients with baseline CDAI scores ≥220 : clinical remission occurred at weeks 4 and 12 in 2 ( 12 % ) and 5 ( 29 % ) , respectively ; and clinical response occurred in 7 ( 41 % ) and 10 ( 59 % ) , respectively . Nineteen patients ( 79 % ) escalated their dose during weeks 4–6 . CONCLUSIONS : Adalimumab is well tolerated and appears to be a clinical ly beneficial option for patients with Crohn 's disease who have previously lost their response to , or can not tolerate infliximab Background : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimumab 40 mg every other week and 83 % who received 40 mg weekly were in remission at week 56 , v 44 % for placebo ( p<0.05 ) . In all , 204 patients entered the open-label arm . Of these , 93 ( 46 % ) were in clinical remission at week 56 . Adalimumab was generally well-tolerated in all patients . Conclusions : Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn ’s disease naive to anti-TNF treatment Background : Data regarding the effectiveness of anti‐tumor necrosis factor ( TNF ) agents for resolution of extraintestinal manifestations ( EIMs ) are scarce . The CARE study evaluated clinical effectiveness , EIM resolution , and safety of adalimumab in a large pan‐European cohort of patients with moderate to severe Crohn 's disease ( CD ) . Methods : In all , 945 patients with a Harvey – Bradshaw Index ( HBI ) ≥7 enrolled in this multicenter , open‐label phase IIIb trial . Patients received subcutaneous adalimumab , 160/80 mg at weeks 0/2 , then 40 mg every other week . Dose adjustments were allowed for CD‐related concomitant medications ( from week 8) and adalimumab ( from week 12 ) . Clinical endpoints were analyzed through week 20 for all patients , and after stratification by prior infliximab exposure and by reason for discontinuing infliximab ( primary nonresponse [ PNR ] or other ) . Results : The remission rate ( HBI < 5 ) at week 20 was 52 % ( 95 % confidence interval , 49%–55 % ) overall , and was higher for infliximab‐naïve versus infliximab‐exposed patients ( 62 % versus 42 % , P < 0.001 ) . Remission rates were similar for PNR ( 37 % ) and other reasons ( 43 % ; P = 0.278 ) . Of 497 patients with baseline EIMs , 51 % were free of EIM signs and symptoms at week 20 . Serious infectious adverse events were reported in 5 % of patients . Opportunistic infections and malignancies were rare ( ≤1 % ) . There was one case of demyelinating disease , but no occurrences of lupus , tuberculosis , or death . Conclusions : In this large cohort of patients , adalimumab treatment result ed in rates of clinical remission and EIM resolution exceeding 50 % , and substantial rates of effectiveness in patients who had PNR to  infliximab . Adalimumab was well tolerated , with safety consistent with prior reports . ( Inflamm Bowel Dis 2011 BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug Aliment Pharmacol Ther 2010 ; 32 : 1228–1239 To evaluate the efficacy and safety of adalimumab , a human antitumour necrosis factor‐α antibody , in induction and maintenance of remission in patients with Crohn ’s disease either refractory or intolerant to infliximab in a single centre cohort BACKGROUND Treatment with infliximab , a chimeric monoclonal IgG1 antibody against tumor necrosis factor , can result in the formation of antibodies against infliximab . We evaluated the clinical significance of these antibodies in patients with Crohn 's disease . METHODS In a cohort of 125 consecutive patients with Crohn 's disease who were treated with infliximab infusions  , we evaluated the concentrations of infliximab and of antibodies against infliximab  , clinical data , side effects ( including infusion reactions ) , and the use of concomitant medications before and 4 , 8 , and 12 weeks after each infusion . RESULTS A mean of 3.9 infusions ( range , 1 to 17 ) per patient were administered over a mean period of 10 months . Antibodies against infliximab  were detected in 61 percent of patients . The presence of concentrations of 8.0 microg per milliliter or greater before an infusion predicted a shorter duration of response ( 35 days , as compared with 71 days among patients with concentrations of less than 8.0 microg per milliliter ; P<0.001 ) and a higher risk of infusion reactions ( relative risk , 2.40 ; 95 percent confidence interval , 1.65 to 3.66 ; P<0.001 ) .  Infliximab concentrations were significantly lower at four weeks among patients who had had an infusion reaction than among patients who had never had an infusion reaction ( median , 1.2 vs. 14.1 microg per milliliter ; P<0.001 ) . Patients who had infusion reactions had a median duration of clinical response of 38.5 days , as compared with 65 days among patients who did not have an infusion reaction ( P<0.001 ) . Concomitant immunosuppressive therapy was predictive of low titers of antibodies against infliximab  ( P<0.001 ) and high concentrations of  infliximab  four weeks after an infusion ( P<0.001 ) . CONCLUSIONS The development of antibodies against infliximab is associated with an increased risk of infusion reactions and a reduced duration of response to treatment . Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response OBJECTIVE To evaluate open-label adalimumab therapy for clinical effectiveness , fistula healing , patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn 's disease ( CD ) who were either naive to or previously exposed to antitumour necrosis factor ( anti-TNF ) therapy . METHODS Patients with moderate to severe CD ( CD activity index [ CDAI ] score of greater than 220 , or Harvey-Bradshaw index [ HBI ] of 7 or greater ) were eligible . Patients received open-label adalimumab as induction ( 160 mg and 80 mg subcutaneously [ sc ] ) at weeks 0 and 2 , respectively and maintenance ( 40 mg sc every other week ) therapy . At or after eight weeks , patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly . Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada . RESULTS Of the 304 patients enrolled , 160 were infliximab experienced , while 144 were anti-TNF naive .  HBI remission ( HBI score of 4 or lower ) at week 24 was achieved by 53 % of anti-TNF-naive and 36 % of infliximab-experienced patients ( P<0.01 ; P<0.001 for both groups for all visits versus baseline ) . Fistula healing rates at week 12 were 48 % for anti-TNF-naive patients , and 26 % for infliximab-experienced patients . At week 24 , fistula healing rates were significantly greater for the anti-TNF-naive group ( 60 % versus 28 % ; P<0.01 ) . Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients . Serious infections occurred in 2 % of patients . CONCLUSIONS Adalimumab therapy induced and sustained steroidfree remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD . Clinical ly meaningful rates of fistula healing were also observed . Improvements in patient-reported outcomes were sustained throughout the 24-week study period BACKGROUND & AIMS Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn 's disease ( CD ) . Adalimumab is a human immunoglobulin G1 ( IgG(1 ) ) monoclonal 
    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 : We assessed the tolerability and clinical benefit of adalimumab , a human antibody to tumor necrosis factor ( TNF ) , in patients with Crohn 's disease who had previously received and responded to the chimeric anti-TNF antibody infliximab , but who no longer had a sustained response and /or tolerance to infliximab . METHODS : A total of 24 patients with Crohn 's disease who had lost responsiveness or developed intolerance ( acute or delayed infusion reactions ) to infliximab  were enrolled in a 12-wk uncontrolled trial and treated with subcutaneous adalimumab 80 mg at week 0 and then 40 mg every other week starting at week 2 . After week 4 , the dose could be escalated to 40 mg weekly in patients who did not achieve clinical remission , complete fistula closure , and complete steroid withdrawal . Outcome measures included the ability to tolerate adalimumab and clinical remission ( defined as a Crohn 's disease activity index ( CDAI ) score ≤150 points ) and clinical response ( defined as a decrease in the CDAI ) ≥100 points ) in patients who had a baseline CDAI score ≥220 . RESULTS : None of the patients experienced acute or delayed hypersensitivity reactions during treatment with adalimumab ( including 14 who previously experienced treatment-limiting acute hypersensitivity reactions and 6 who previously experienced delayed hypersensitivity reactions with infliximab ) . Of 17 patients with baseline CDAI scores ≥220 : clinical remission occurred at weeks 4 and 12 in 2 ( 12 % ) and 5 ( 29 % ) , respectively ; and clinical response occurred in 7 ( 41 % ) and 10 ( 59 % ) , respectively . Nineteen patients ( 79 % ) escalated their dose during weeks 4–6 . CONCLUSIONS : Adalimumab is well tolerated and appears to be a clinical ly beneficial option for patients with Crohn 's disease who have previously lost their response to , or can not tolerate infliximab Background : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimumab 40 mg every other week and 83 % who received 40 mg weekly were in remission at week 56 , v 44 % for placebo ( p<0.05 ) . In all , 204 patients entered the open-label arm . Of these , 93 ( 46 % ) were in clinical remission at week 56 . Adalimumab was generally well-tolerated in all patients . Conclusions : Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn ’s disease naive to anti-TNF treatment Background : Data regarding the effectiveness of anti‐tumor necrosis factor ( TNF ) agents for resolution of extraintestinal manifestations ( EIMs ) are scarce . The CARE study evaluated clinical effectiveness , EIM resolution , and safety of adalimumab in a large pan‐European cohort of patients with moderate to severe Crohn 's disease ( CD ) . Methods : In all , 945 patients with a Harvey – Bradshaw Index ( HBI ) ≥7 enrolled in this multicenter , open‐label phase IIIb trial . Patients received subcutaneous adalimumab , 160/80 mg at weeks 0/2 , then 40 mg every other week . Dose adjustments were allowed for CD‐related concomitant medications ( from week 8) and adalimumab ( from week 12 ) . Clinical endpoints were analyzed through week 20 for all patients , and after stratification by prior infliximab exposure and by reason for discontinuing infliximab ( primary nonresponse [ PNR ] or other ) . Results : The remission rate ( HBI < 5 ) at week 20 was 52 % ( 95 % confidence interval , 49%–55 % ) overall , and was higher for infliximab‐naïve versus infliximab‐exposed patients ( 62 % versus 42 % , P < 0.001 ) . Remission rates were similar for PNR ( 37 % ) and other reasons ( 43 % ; P = 0.278 ) . Of 497 patients with baseline EIMs , 51 % were free of EIM signs and symptoms at week 20 . Serious infectious adverse events were reported in 5 % of patients . Opportunistic infections and malignancies were rare ( ≤1 % ) . There was one case of demyelinating disease , but no occurrences of lupus , tuberculosis , or death . Conclusions : In this large cohort of patients , adalimumab treatment result ed in rates of clinical remission and EIM resolution exceeding 50 % , and substantial rates of effectiveness in patients who had PNR to  infliximab . Adalimumab was well tolerated , with safety consistent with prior reports . ( Inflamm Bowel Dis 2011 BACKGROUND & AIMS This study evaluated the efficacy and safety of adalimumab , a fully human , anti-tumor necrosis factor monoclonal antibody administered subcutaneously , in the maintenance of response and remission in patients with moderate to severe Crohn 's disease ( CD ) . METHODS Patients received open-label induction therapy with adalimumab 80 mg ( week 0 ) followed by 40 mg ( week 2 ) . At week 4 , patients were stratified by response ( decrease in Crohn 's Disease Activity Index > or = 70 points from baseline ) and r and omized to double-blind treatment with placebo , adalimumab 40 mg every other week ( eow ) , or adalimumab 40 mg weekly through week 56 . Co- primary end points were the percentages of r and omized responders who achieved clinical remission ( Crohn 's Disease Activity Index score < 150 ) at weeks 26 and 56 . RESULTS The percentage of r and omized responders in remission was significantly greater in the adalimumab 40-mg eow and 40-mg weekly groups versus placebo at week 26 ( 40 % , 47 % , and 17 % , respectively ; P < .001 ) and week 56 ( 36 % , 41 % , and 12 % , respectively ; P < .001 ) . No significant differences in efficacy between adalimumab eow and weekly were observed . More patients receiving placebo discontinued treatment because of an adverse event ( 13.4 % ) than those receiving adalimumab ( 6.9 % and 4.7 % in the 40-mg eow and 40-mg weekly groups , respectively ) . CONCLUSIONS Among patients who responded to adalimumab  , both adalimumab eow and weekly were significantly more effective than placebo in maintaining remission in moderate to severe CD through 56 weeks . Adalimumab was well-tolerated , with a safety profile consistent with previous experience with the drug Aliment Pharmacol Ther 2010 ; 32 : 1228–1239 To evaluate the efficacy and safety of adalimumab , a human antitumour necrosis factor‐α antibody , in induction and maintenance of remission in patients with Crohn ’s disease either refractory or intolerant to infliximab in a single centre cohort BACKGROUND Treatment with infliximab , a chimeric monoclonal IgG1 antibody against tumor necrosis factor , can result in the formation of antibodies against infliximab . We evaluated the clinical significance of these antibodies in patients with Crohn 's disease . METHODS In a cohort of 125 consecutive patients with Crohn 's disease who were treated with infliximab infusions  , we evaluated the concentrations of infliximab and of antibodies against infliximab  , clinical data , side effects ( including infusion reactions ) , and the use of concomitant medications before and 4 , 8 , and 12 weeks after each infusion . RESULTS A mean of 3.9 infusions ( range , 1 to 17 ) per patient were administered over a mean period of 10 months . Antibodies against infliximab  were detected in 61 percent of patients . The presence of concentrations of 8.0 microg per milliliter or greater before an infusion predicted a shorter duration of response ( 35 days , as compared with 71 days among patients with concentrations of less than 8.0 microg per milliliter ; P<0.001 ) and a higher risk of infusion reactions ( relative risk , 2.40 ; 95 percent confidence interval , 1.65 to 3.66 ; P<0.001 ) .  Infliximab concentrations were significantly lower at four weeks among patients who had had an infusion reaction than among patients who had never had an infusion reaction ( median , 1.2 vs. 14.1 microg per milliliter ; P<0.001 ) . Patients who had infusion reactions had a median duration of clinical response of 38.5 days , as compared with 65 days among patients who did not have an infusion reaction ( P<0.001 ) . Concomitant immunosuppressive therapy was predictive of low titers of antibodies against infliximab  ( P<0.001 ) and high concentrations of  infliximab  four weeks after an infusion ( P<0.001 ) . CONCLUSIONS The development of antibodies against infliximab is associated with an increased risk of infusion reactions and a reduced duration of response to treatment . Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response OBJECTIVE To evaluate open-label adalimumab therapy for clinical effectiveness , fistula healing , patient-reported outcomes and safety in Canadian patients with moderate to severe Crohn 's disease ( CD ) who were either naive to or previously exposed to antitumour necrosis factor ( anti-TNF ) therapy . METHODS Patients with moderate to severe CD ( CD activity index [ CDAI ] score of greater than 220 , or Harvey-Bradshaw index [ HBI ] of 7 or greater ) were eligible . Patients received open-label adalimumab as induction ( 160 mg and 80 mg subcutaneously [ sc ] ) at weeks 0 and 2 , respectively and maintenance ( 40 mg sc every other week ) therapy . At or after eight weeks , patients with flare or nonresponse could have their dosage increased to 40 mg sc weekly . Patients were followed for a minimum of six months or until adalimumab was commercially available in Canada . RESULTS Of the 304 patients enrolled , 160 were infliximab experienced , while 144 were anti-TNF naive .  HBI remission ( HBI score of 4 or lower ) at week 24 was achieved by 53 % of anti-TNF-naive and 36 % of infliximab-experienced patients ( P<0.01 ; P<0.001 for both groups for all visits versus baseline ) . Fistula healing rates at week 12 were 48 % for anti-TNF-naive patients , and 26 % for infliximab-experienced patients . At week 24 , fistula healing rates were significantly greater for the anti-TNF-naive group ( 60 % versus 28 % ; P<0.01 ) . Improvements in quality of life and work productivity were sustained from week 4 to week 24 for all patients . Serious infections occurred in 2 % of patients . CONCLUSIONS Adalimumab therapy induced and sustained steroidfree remission in both infliximab-experienced and anti-TNF-naive patients with moderate to severe CD . Clinical ly meaningful rates of fistula healing were also observed . Improvements in patient-reported outcomes were sustained throughout the 24-week study period BACKGROUND & AIMS Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn 's disease ( CD ) . Adalimumab is a human immunoglobulin G1 ( IgG(1 ) ) monoclonal 
    Output:
    