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 did a r and omised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn 's disease who respond to a single infusion of infliximab .  METHODS 573 patients with a score of at least 220 on the Crohn 's disease activity index ( CDAI ) received a 5 mg/kg intravenous infusion of infliximab at week 0 . After assessment of response at week 2 , patients were r and omly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 ( group I ) , repeat infusions of 5 mg/kg infliximab at the same timepoints ( group II ) , or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg ( group III ) . The prespecified co- primary endpoints were the proportion of patients who responded at week 2 and were in remission ( CDAI < 150 ) at week 30 and the time to loss of response up to week 54 in patients who responded . Analyses of the co- primary endpoints were by intention to treat . FINDINGS 335 ( 58 % ) patients responded to a single infusion of infliximab within 2 weeks . At week 30 , 23 of 110 ( 21 % ) group I patients were in remission , compared with 44 of 113 ( 39 % ) group II ( p=0.003 ) and 50 of 112 ( 45 % ) group III ( p=0.0002 ) patients . Thus , patients in groups II and III combined were more likely to sustain clinical remission than patients in group I ( odds ratio 2.7 , 95 % CI 1.6 - 4.6 ) . Throughout the 54-week trial , the median time to loss of response was 38 weeks ( IQR 15 to > 54 ) and more than 54 weeks ( 21 to > 54 ) for groups II and III , respectively , compared with 19 weeks ( 10 - 45 ) for group I ( p=0.002 and p=0.0002 , respectively ) .  Infliximab safety was consistent with that seen in other trials of infliximab in Crohn 's disease and rheumatoid arthritis . In particular , the incidence of serious infections was similar across treatment groups . INTERPRETATION Patients with Crohn 's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54 , to discontinue corticosteroids , and to maintain their response for a longer period of time , if infliximab treatment is maintained every 8 weeks BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients Background : The aim of this study was to evaluate the short‐ and long‐term safety experience of infliximab treatment in patients with Crohn 's disease ( CD ) in clinical practice . Methods : The medical records of 297 consecutive patients with CD treated with infliximab at the Beth Israel Deaconess Medical Center were review ed for demographic features and adverse events . Results : The 297 patients received a total of 1794 infusions . Patients received a median of four infusions and had a median follow‐up of 14.3 months . Forty‐four patients ( 15 % ) experienced a serious adverse event , requiring the infusion to be stopped in 33 patients ( 11 % ) . Acute infusion reactions occurred in 18 patients ( 6 % ) including respiratory problems in 10 patients ( 3 % ) and an anaphylactoid reaction in 1 patient ( 0.3 % ) . Serum sickness‐like disease occurred in one patient ( 0.3 % ) and three patients ( 1 % ) developed drug‐induced lupus . One patient developed a probable new demyelination disorder . Eight patients ( 2.7 % ) , all of whom were on concurrent immunosuppressants , developed a serious infection , one result ing in fatal sepsis . Six patients ( 2 % ) developed malignancies including two lymphomas and two skin cancers . A total of four ( 1.3 % ) deaths were observed ( median age 72.5 years ) ; two due to gastrointestinal bleeding , one due to sepsis , and one due to malignancy . Conclusions : While short‐ and long‐term infliximab therapy was generally well tolerated , serious adverse events occurred in 15 % of patients including drug‐induced lupus , fatal sepsis , and malignancy . Concomitant immunosuppressants were significantly associated with infections and deaths , particularly among elderly patients . ( Inflamm Bowel Dis 2010 BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . BACKGROUND Infliximab , a monoclonal antibody against tumor necrosis factor , is an effective maintenance therapy for patients with Crohn 's disease without fistulas . It is not known whether infliximab is an effective maintenance therapy for patients with fistulas . METHODS We performed a multicenter , double-blind , r and omized , placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn 's disease and one or more draining abdominal or perianal fistulas of at least three months ' duration . Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0 , 2 , and 6 . A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then r and omly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54 . The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent r and omization . RESULTS The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance ( more than 40 weeks vs. 14 weeks , P<0.001 ) . At week 54 , 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas , as compared with 36 percent of patients in the infliximab maintenance group ( P=0.009 ) . CONCLUSIONS Patients with fistulizing Crohn 's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks BACKGROUND & AIMS The benefit to risk ratio of concomitant immunosuppressives with scheduled infliximab ( IFX ) maintenance therapy for Crohn 's disease is an issue of debate . We aim ed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label , r and omized , controlled trial . METHODS Patients with controlled disease > or = 6 months after the start of IFX ( 5 mg/kg intravenously ) combined with immunosuppressives were r and omized to continue ( Con ) or to interrupt ( Dis ) immunosuppressives , while all patients received scheduled IFX maintenance therapy for 104 weeks . Primary end point was the proportion of patients who required a decrease in  IFX dosing interval or stopped IFX therapy . Secondary end points included IFX trough levels , safety , and mucosal healing . RESULTS A similar proportion ( 24/40 , 60 % Con ) and ( 22/40 , 55 % Dis ) of patients needed a change in  IFX dosing interval or stopped IFX  therapy ( 11/40 Con , 9/40 Dis ) . C-reactive protein ( CRP ) was higher and IFX trough levels were lower in the Dis group ( Dis : CRP , 2.8 mg/L ; interquartile range [ IQR ] , 1.0 - 8.0 ; Con : CRP , 1.6 mg/L ; IQR , 1.0 - 5.6 , P < .005 ; trough IFX : Dis : 1.65 microg/mL ; IQR , 0.54 - 3.68 ; Con : 2.87 microg/mL ; IQR , 1.35 - 4.72 , P < .0001 ) . Low IFX trough levels correlated with increased CRP and clinical score . Mucosal ulcers were absent at week 104 in 64 % ( Con ) and 61 % ( Dis ) of evaluated patients with ongoing response to IFX . CONCLUSIONS Continuation of immunosuppressives beyond 6 months offers no clear benefit over scheduled IFX monotherapy but is associated with higher median IFX trough and decreased CRP levels . The impact of these observations on long-term outcomes needs to be explored further BACKGROUND Enterocutaneous fistulas are a serious complication of Crohn 's disease and are difficult to treat . Infliximab , a chimeric monoclonal antibody to tumor necrosis factor alpha , has recently been developed as a treatment for Crohn 's disease . We conducted a r and omized , multicenter , double-blind , placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn 's disease . METHODS The study included 94 adult patients who had draining abdominal or perianal fistulas of 
    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 did a r and omised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn 's disease who respond to a single infusion of infliximab .  METHODS 573 patients with a score of at least 220 on the Crohn 's disease activity index ( CDAI ) received a 5 mg/kg intravenous infusion of infliximab at week 0 . After assessment of response at week 2 , patients were r and omly assigned repeat infusions of placebo at weeks 2 and 6 and then every 8 weeks thereafter until week 46 ( group I ) , repeat infusions of 5 mg/kg infliximab at the same timepoints ( group II ) , or 5 mg/kg infliximab at weeks 2 and 6 followed by 10 mg/kg ( group III ) . The prespecified co- primary endpoints were the proportion of patients who responded at week 2 and were in remission ( CDAI < 150 ) at week 30 and the time to loss of response up to week 54 in patients who responded . Analyses of the co- primary endpoints were by intention to treat . FINDINGS 335 ( 58 % ) patients responded to a single infusion of infliximab within 2 weeks . At week 30 , 23 of 110 ( 21 % ) group I patients were in remission , compared with 44 of 113 ( 39 % ) group II ( p=0.003 ) and 50 of 112 ( 45 % ) group III ( p=0.0002 ) patients . Thus , patients in groups II and III combined were more likely to sustain clinical remission than patients in group I ( odds ratio 2.7 , 95 % CI 1.6 - 4.6 ) . Throughout the 54-week trial , the median time to loss of response was 38 weeks ( IQR 15 to > 54 ) and more than 54 weeks ( 21 to > 54 ) for groups II and III , respectively , compared with 19 weeks ( 10 - 45 ) for group I ( p=0.002 and p=0.0002 , respectively ) .  Infliximab safety was consistent with that seen in other trials of infliximab in Crohn 's disease and rheumatoid arthritis . In particular , the incidence of serious infections was similar across treatment groups . INTERPRETATION Patients with Crohn 's disease who respond to an initial dose of infliximab are more likely to be in remission at weeks 30 and 54 , to discontinue corticosteroids , and to maintain their response for a longer period of time , if infliximab treatment is maintained every 8 weeks BACKGROUND & AIMS The aim of this study was to evaluate the usefulness of short-term infliximab combined with azathioprine ( AZA ) or 6-mercaptopurine ( 6-MP ) in steroid-dependent Crohn 's disease patients . METHODS Patients with active disease despite prednisone given for more than 6 months were eligible and were stratified as follows : the failure stratum consisted of patients receiving AZA/6-MP at a stable dose for more than 6 months , and the naive stratum consisted of patients not treated previously with AZA/6-MP . Patients were r and omized to infliximab 5 mg/kg or placebo at weeks 0 , 2 , and 6 . All patients were treated with AZA/6-MP maintained at a stable dose throughout the 52 weeks of the study . The primary end point was remission off steroids at week 24 . RESULTS Among the 113 enrolled patients ( 55 in the failure stratum ) , 57 were assigned to infliximab . At week 24 , the success rate ( intent-to-treat analysis ) was higher in the infliximab group than in the placebo group ( 57 % vs 29 % ; P = .003 ) ; at weeks 12 and 52 , the corresponding rates were 75 % vs 38 % ( P < .001 ) and 40 % vs 22 % ( P = .04 ) , respectively . In each stratum , the success rate was significantly higher in the infliximab group at weeks 12 and 24 , and a trend was found at week 52 . In the failure stratum , only 27 % of the patients in the infliximab group were still in remission off steroids , compared with 52 % in the naive stratum . Steroid resistance was less common and the cumulative dose of prednisone was lower in the infliximab group . CONCLUSIONS Infliximab plus AZA/6-MP is more effective than AZA/6-MP alone in steroid-dependent Crohn 's disease patients Background : The aim of this study was to evaluate the short‐ and long‐term safety experience of infliximab treatment in patients with Crohn 's disease ( CD ) in clinical practice . Methods : The medical records of 297 consecutive patients with CD treated with infliximab at the Beth Israel Deaconess Medical Center were review ed for demographic features and adverse events . Results : The 297 patients received a total of 1794 infusions . Patients received a median of four infusions and had a median follow‐up of 14.3 months . Forty‐four patients ( 15 % ) experienced a serious adverse event , requiring the infusion to be stopped in 33 patients ( 11 % ) . Acute infusion reactions occurred in 18 patients ( 6 % ) including respiratory problems in 10 patients ( 3 % ) and an anaphylactoid reaction in 1 patient ( 0.3 % ) . Serum sickness‐like disease occurred in one patient ( 0.3 % ) and three patients ( 1 % ) developed drug‐induced lupus . One patient developed a probable new demyelination disorder . Eight patients ( 2.7 % ) , all of whom were on concurrent immunosuppressants , developed a serious infection , one result ing in fatal sepsis . Six patients ( 2 % ) developed malignancies including two lymphomas and two skin cancers . A total of four ( 1.3 % ) deaths were observed ( median age 72.5 years ) ; two due to gastrointestinal bleeding , one due to sepsis , and one due to malignancy . Conclusions : While short‐ and long‐term infliximab therapy was generally well tolerated , serious adverse events occurred in 15 % of patients including drug‐induced lupus , fatal sepsis , and malignancy . Concomitant immunosuppressants were significantly associated with infections and deaths , particularly among elderly patients . ( Inflamm Bowel Dis 2010 BACKGROUND The comparative efficacy and safety of infliximab and azathioprine therapy alone or in combination for Crohn 's disease are unknown . METHODS In this r and omized , double-blind trial , we evaluated the efficacy of infliximab monotherapy , azathioprine monotherapy , and the two drugs combined in 508 adults with moderate-to-severe Crohn 's disease who had not undergone previous immunosuppressive or biologic therapy . Patients were r and omly assigned to receive an intravenous infusion of 5 mg of infliximab per kilogram of body weight at weeks 0 , 2 , and 6 and then every 8 weeks plus daily oral placebo capsules ; 2.5 mg of oral azathioprine per kilogram daily plus a placebo infusion on the st and ard schedule ; or combination therapy with the two drugs . Patients received study medication through week 30 and could continue in a blinded study extension through week 50 . RESULTS Of the 169 patients receiving combination therapy , 96 ( 56.8 % ) were in corticosteroid-free clinical remission at week 26 ( the primary end point ) , as compared with 75 of 169 patients ( 44.4 % ) receiving infliximab alone ( P=0.02 ) and 51 of 170 patients ( 30.0 % ) receiving azathioprine alone ( P<0.001 for the comparison with combination therapy and P=0.006 for the comparison with infliximab ) . Similar numerical trends were found at week 50 . At week 26 , mucosal healing had occurred in 47 of 107 patients ( 43.9 % ) receiving combination therapy , as compared with 28 of 93 patients ( 30.1 % ) receiving infliximab ( P=0.06 ) and 18 of 109 patients ( 16.5 % ) receiving azathioprine ( P<0.001 for the comparison with combination therapy and P=0.02 for the comparison with infliximab ) . Serious infections developed in 3.9 % of patients in the combination-therapy group , 4.9 % of those in the infliximab group , and 5.6 % of those in the azathioprine group . CONCLUSIONS Patients with moderate-to-severe Crohn 's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy . ( Clinical Trials.gov number , NCT00094458 . BACKGROUND Infliximab , a monoclonal antibody against tumor necrosis factor , is an effective maintenance therapy for patients with Crohn 's disease without fistulas . It is not known whether infliximab is an effective maintenance therapy for patients with fistulas . METHODS We performed a multicenter , double-blind , r and omized , placebo-controlled trial to evaluate the efficacy of infliximab maintenance therapy in 306 adult patients with Crohn 's disease and one or more draining abdominal or perianal fistulas of at least three months ' duration . Patients received 5 mg of infliximab per kilogram of body weight intravenously on weeks 0 , 2 , and 6 . A total of 195 patients who had a response at weeks 10 and 14 and 87 patients who had no response were then r and omly assigned to receive placebo or 5 mg of infliximab per kilogram every eight weeks and to be followed to week 54 . The primary analysis was the time to the loss of response among patients who had a response at week 14 and underwent r and omization . RESULTS The time to loss of response was significantly longer for patients who received infliximab maintenance therapy than for those who received placebo maintenance ( more than 40 weeks vs. 14 weeks , P<0.001 ) . At week 54 , 19 percent of patients in the placebo maintenance group had a complete absence of draining fistulas , as compared with 36 percent of patients in the infliximab maintenance group ( P=0.009 ) . CONCLUSIONS Patients with fistulizing Crohn 's disease who have a response to induction therapy with infliximab have an increased likelihood of a sustained response over a 54-week period if infliximab treatment is continued every 8 weeks BACKGROUND & AIMS The benefit to risk ratio of concomitant immunosuppressives with scheduled infliximab ( IFX ) maintenance therapy for Crohn 's disease is an issue of debate . We aim ed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label , r and omized , controlled trial . METHODS Patients with controlled disease > or = 6 months after the start of IFX ( 5 mg/kg intravenously ) combined with immunosuppressives were r and omized to continue ( Con ) or to interrupt ( Dis ) immunosuppressives , while all patients received scheduled IFX maintenance therapy for 104 weeks . Primary end point was the proportion of patients who required a decrease in  IFX dosing interval or stopped IFX therapy . Secondary end points included IFX trough levels , safety , and mucosal healing . RESULTS A similar proportion ( 24/40 , 60 % Con ) and ( 22/40 , 55 % Dis ) of patients needed a change in  IFX dosing interval or stopped IFX  therapy ( 11/40 Con , 9/40 Dis ) . C-reactive protein ( CRP ) was higher and IFX trough levels were lower in the Dis group ( Dis : CRP , 2.8 mg/L ; interquartile range [ IQR ] , 1.0 - 8.0 ; Con : CRP , 1.6 mg/L ; IQR , 1.0 - 5.6 , P < .005 ; trough IFX : Dis : 1.65 microg/mL ; IQR , 0.54 - 3.68 ; Con : 2.87 microg/mL ; IQR , 1.35 - 4.72 , P < .0001 ) . Low IFX trough levels correlated with increased CRP and clinical score . Mucosal ulcers were absent at week 104 in 64 % ( Con ) and 61 % ( Dis ) of evaluated patients with ongoing response to IFX . CONCLUSIONS Continuation of immunosuppressives beyond 6 months offers no clear benefit over scheduled IFX monotherapy but is associated with higher median IFX trough and decreased CRP levels . The impact of these observations on long-term outcomes needs to be explored further BACKGROUND Enterocutaneous fistulas are a serious complication of Crohn 's disease and are difficult to treat . Infliximab , a chimeric monoclonal antibody to tumor necrosis factor alpha , has recently been developed as a treatment for Crohn 's disease . We conducted a r and omized , multicenter , double-blind , placebo-controlled trial of infliximab for the treatment of fistulas in patients with Crohn 's disease . METHODS The study included 94 adult patients who had draining abdominal or perianal fistulas of 
    Output:
    