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 Goals To assess the efficacy and safety profile of methotrexate ( MTX ) for the treatment of Crohn 's disease ( CD ) in clinical practice . Background MTX is widely used for some chronic immunologic diseases . Although some r and omized controlled trials suggest its efficacy in CD , this drug remains a second-line , underused , immunomodulator . Study Medical records of all patients treated with MTX for CD in our center ( n=44 ) were review ed . Clinical and epidemiologic parameters , including risk factors for hepatotoxicity , were registered . Results MTX was prescribed mainly for steroid-dependency ( n=22 ) and as concomitant treatment to infliximab ( n=18 ) . Mean duration of treatment was 22.9±19 months , with a mean cumulative dose of MTX of 1169±784 mg . Thirty-nine percent of patients developed drug-related side effects , hepatotoxicity being the most frequent [ 13 patients ( 30 % ) ] . However , only 5 patients ( 11 % ) had to discontinue MTX . In steroid-dependent CD patients  , disease remission and complete steroid withdrawal was achieved in 77 % of cases . Seven patients lost their initial response to MTX during follow-up , leading to a cumulative probability of remission of 39 % after 3 years of treatment . Conclusions MTX is well tolerated in most CD patients . Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal , there is a trend to a loss of efficacy with time . Larger , long-term studies are necessary to establish the role of MTX in the management of CD BACKGROUND / AIMS Immunosuppression with methotrexate may be useful in the treatment of Crohn 's disease . We tested the efficacy of methotrexate in refractory Crohn 's disease in a r and omized , controlled trial . METHODOLOGY R and omized , double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn 's disease , 33 % of whom had previously failed therapy with 6-mercaptopurine .  Patients were given placebo or oral methotrexate 15 mg/week , or adjusted up to 22.5 mg/week , for up to 1 year or until treatment failure . Outcome was assessed by reduction in prednisone dosage , Crohn 's Disease Activity Index , hospital admission , and laboratory parameters . RESULTS Four patients were dropped from the study for non-compliance and one because of intercurrent illness , and 28 patients could be evaluated . Fewer methotrexate-treated patients ( 6/13 or 46 % ) had flares of Crohn 's disease as compared to placebo-treated patients ( 12/15 or 80 % ) , but this did not achieve statistical significance ( p<0.1 ) . There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients ( 3/13 or 23 % ) as compared to the placebo-treated patients ( 0/15 or 0 % ) ( p<0.2 ) . Laboratory indices of inflammation did not differ between the two groups . CONCLUSIONS The  methotrexate-treated  group showed a trend toward fewer Crohn 's disease flares , balanced by an increased number of significant side effects 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 BACKGROUND Although corticosteroids are highly effective in improving symptoms of Crohn 's disease , they may have substantial toxicity . In some patients , attempts to discontinue corticosteroids are unsuccessful . METHODS We conducted a double-blind , placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn 's disease despite a minimum of three months of prednisone therapy . Patients were r and omly assigned to treatment with intramuscular methotrexate ( 25 mg once weekly ) or placebo for 16 weeks . The patients also received prednisone ( 20 mg once a day ) , which was tapered over 10 weeks unless their condition worsened . The primary outcome measure was clinical remission at the end of the 16-week trial . Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn 's Disease Activity Index . RESULTS A total of 141 patients were r and omly assigned in a 2:1 ratio to  methotrexate ( 94 patients ) or placebo ( 47 patients ) . After 16 weeks , 37 patients ( 39.4 percent ) were in clinical remission in the methotrexate group , as compared with 9 patients ( 19.1 percent ) in the placebo group ( P = 0.025 ; relative risk , 1.95 ; 95 percent confidence interval , 1.09 to 3.48 ) . The patients in the methotrexate group received less  prednisone  overall than those in the placebo group ( P = 0.026 ) . The mean ( + /- SE ) score on the Crohn 's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group ( 162 + /- 12 ) than in the placebo group ( 204 + /- 17 , P = 0.002 ) . The changes in quality -of-life scores and serum orosomucoid concentrations were similar . In the methotrexate group , 16 patients ( 17 percent ) withdrew from treatment because of adverse events ( including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6 ) , as compared with 1 patient ( 2 percent ) in the placebo group . CONCLUSIONS In a group of patients with chronically active Crohn 's disease , methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone Background As treatment of steroid‐dependent patients with inflammatory bowel disease ( IBD ) is controversial , we analysed the efficacy and tolerance of 6‐mercaptopurine ( 6‐MP ) and methotrexate ( MTX ) added to prednisone in increasing and maintaining the disease remission rate . Methods Seventy‐two steroid‐dependent IBD patients , 34 with ulcerative colitis ( UC ) and 38 with Crohn 's disease ( CD ) , receiving treatment with prednisone  were r and omly assigned in a 2:2:1 ratio to additionally receive , orally , over a period of 30 weeks 1.5 mg/kg/day of 6‐MP ( group A ) or 15 mg/week of MTX ( group B ) , or 3 g/day of 5‐aminosalicylic acid ( 5‐ASA ) ( group C ) . All patients who achieved remission were included in a maintaining remission study for 76 weeks . Remission was defined after stopping prednisone as a CD activity index of < 150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score < 7 for UC patients . Results With regard to achieved remission , a significantly higher ( P < 0.05 ) rate existed for UC patients in group A ( 78.6 % ) than in group C ( 25 % ) , with no statistical differences in group B ( 58.3 % ) versus C. For CD patients , the rates were significantly higher ( P < 0.001 and 0.01 , respectively ) in groups A ( 93.7 % ) and B ( 80 % ) versus C ( 14 % ) . With regard to maintaining remission , UC patients in group A ( 63.6 % ) presented significantly higher rates ( P < 0.0015 and P < 0.001 , respectively ) versus 14.3 % in group B and none in group C. For CD patients , statistical differences ( P < 0.001 ) existed when comparing rates in groups A ( 53.3 % ) and B ( 66.6 % ) versus none in group C. Noticeable side effects appeared in 13.3 % of patients from group A and 11.5 % from group B. Conclusions These results suggest that 6‐MP or MTX added to prednisone could be effective in steroid sparing , as well as in achieving and maintaining remission in steroid‐dependent IBD patients . MTX was less effective in maintaining remission in UC patients BACKGROUND AND AIMS The efficacy of azathioprine in the treatment of chronic active Crohn 's disease is well established . However , this drug has a long onset of action . Methotrexate has also been shown to be effective in chronic active Crohn 's disease . The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine , and to establish whether methotrexate has a shorter onset of action in this setting . METHODS Patients with chronic active Crohn 's disease were 
    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 Goals To assess the efficacy and safety profile of methotrexate ( MTX ) for the treatment of Crohn 's disease ( CD ) in clinical practice . Background MTX is widely used for some chronic immunologic diseases . Although some r and omized controlled trials suggest its efficacy in CD , this drug remains a second-line , underused , immunomodulator . Study Medical records of all patients treated with MTX for CD in our center ( n=44 ) were review ed . Clinical and epidemiologic parameters , including risk factors for hepatotoxicity , were registered . Results MTX was prescribed mainly for steroid-dependency ( n=22 ) and as concomitant treatment to infliximab ( n=18 ) . Mean duration of treatment was 22.9±19 months , with a mean cumulative dose of MTX of 1169±784 mg . Thirty-nine percent of patients developed drug-related side effects , hepatotoxicity being the most frequent [ 13 patients ( 30 % ) ] . However , only 5 patients ( 11 % ) had to discontinue MTX . In steroid-dependent CD patients  , disease remission and complete steroid withdrawal was achieved in 77 % of cases . Seven patients lost their initial response to MTX during follow-up , leading to a cumulative probability of remission of 39 % after 3 years of treatment . Conclusions MTX is well tolerated in most CD patients . Although a great proportion of steroid-dependent CD patients achieve disease remission and steroid withdrawal , there is a trend to a loss of efficacy with time . Larger , long-term studies are necessary to establish the role of MTX in the management of CD BACKGROUND / AIMS Immunosuppression with methotrexate may be useful in the treatment of Crohn 's disease . We tested the efficacy of methotrexate in refractory Crohn 's disease in a r and omized , controlled trial . METHODOLOGY R and omized , double-blind placebo-controlled trial of methotrexate in 33 patients with steroid-dependent Crohn 's disease , 33 % of whom had previously failed therapy with 6-mercaptopurine .  Patients were given placebo or oral methotrexate 15 mg/week , or adjusted up to 22.5 mg/week , for up to 1 year or until treatment failure . Outcome was assessed by reduction in prednisone dosage , Crohn 's Disease Activity Index , hospital admission , and laboratory parameters . RESULTS Four patients were dropped from the study for non-compliance and one because of intercurrent illness , and 28 patients could be evaluated . Fewer methotrexate-treated patients ( 6/13 or 46 % ) had flares of Crohn 's disease as compared to placebo-treated patients ( 12/15 or 80 % ) , but this did not achieve statistical significance ( p<0.1 ) . There was a non-significant trend toward an increased number of significant side effects in the methotrexate-treated patients ( 3/13 or 23 % ) as compared to the placebo-treated patients ( 0/15 or 0 % ) ( p<0.2 ) . Laboratory indices of inflammation did not differ between the two groups . CONCLUSIONS The  methotrexate-treated  group showed a trend toward fewer Crohn 's disease flares , balanced by an increased number of significant side effects 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 BACKGROUND Although corticosteroids are highly effective in improving symptoms of Crohn 's disease , they may have substantial toxicity . In some patients , attempts to discontinue corticosteroids are unsuccessful . METHODS We conducted a double-blind , placebo-controlled multicenter study of weekly injections of methotrexate in patients who had chronically active Crohn 's disease despite a minimum of three months of prednisone therapy . Patients were r and omly assigned to treatment with intramuscular methotrexate ( 25 mg once weekly ) or placebo for 16 weeks . The patients also received prednisone ( 20 mg once a day ) , which was tapered over 10 weeks unless their condition worsened . The primary outcome measure was clinical remission at the end of the 16-week trial . Remission was defined by the discontinuation of prednisone and a score of < or = 150 points on the Crohn 's Disease Activity Index . RESULTS A total of 141 patients were r and omly assigned in a 2:1 ratio to  methotrexate ( 94 patients ) or placebo ( 47 patients ) . After 16 weeks , 37 patients ( 39.4 percent ) were in clinical remission in the methotrexate group , as compared with 9 patients ( 19.1 percent ) in the placebo group ( P = 0.025 ; relative risk , 1.95 ; 95 percent confidence interval , 1.09 to 3.48 ) . The patients in the methotrexate group received less  prednisone  overall than those in the placebo group ( P = 0.026 ) . The mean ( + /- SE ) score on the Crohn 's Disease Activity Index after 16 weeks of treatment was significantly lower in the methotrexate group ( 162 + /- 12 ) than in the placebo group ( 204 + /- 17 , P = 0.002 ) . The changes in quality -of-life scores and serum orosomucoid concentrations were similar . In the methotrexate group , 16 patients ( 17 percent ) withdrew from treatment because of adverse events ( including asymptomatic elevation of serum aminotransferase in 7 and nausea in 6 ) , as compared with 1 patient ( 2 percent ) in the placebo group . CONCLUSIONS In a group of patients with chronically active Crohn 's disease , methotrexate was more effective than placebo in improving symptoms and reducing requirements for prednisone Background As treatment of steroid‐dependent patients with inflammatory bowel disease ( IBD ) is controversial , we analysed the efficacy and tolerance of 6‐mercaptopurine ( 6‐MP ) and methotrexate ( MTX ) added to prednisone in increasing and maintaining the disease remission rate . Methods Seventy‐two steroid‐dependent IBD patients , 34 with ulcerative colitis ( UC ) and 38 with Crohn 's disease ( CD ) , receiving treatment with prednisone  were r and omly assigned in a 2:2:1 ratio to additionally receive , orally , over a period of 30 weeks 1.5 mg/kg/day of 6‐MP ( group A ) or 15 mg/week of MTX ( group B ) , or 3 g/day of 5‐aminosalicylic acid ( 5‐ASA ) ( group C ) . All patients who achieved remission were included in a maintaining remission study for 76 weeks . Remission was defined after stopping prednisone as a CD activity index of < 150 and normal serum orosomucoid concentration for CD patients and a Mayo Clinic score < 7 for UC patients . Results With regard to achieved remission , a significantly higher ( P < 0.05 ) rate existed for UC patients in group A ( 78.6 % ) than in group C ( 25 % ) , with no statistical differences in group B ( 58.3 % ) versus C. For CD patients , the rates were significantly higher ( P < 0.001 and 0.01 , respectively ) in groups A ( 93.7 % ) and B ( 80 % ) versus C ( 14 % ) . With regard to maintaining remission , UC patients in group A ( 63.6 % ) presented significantly higher rates ( P < 0.0015 and P < 0.001 , respectively ) versus 14.3 % in group B and none in group C. For CD patients , statistical differences ( P < 0.001 ) existed when comparing rates in groups A ( 53.3 % ) and B ( 66.6 % ) versus none in group C. Noticeable side effects appeared in 13.3 % of patients from group A and 11.5 % from group B. Conclusions These results suggest that 6‐MP or MTX added to prednisone could be effective in steroid sparing , as well as in achieving and maintaining remission in steroid‐dependent IBD patients . MTX was less effective in maintaining remission in UC patients BACKGROUND AND AIMS The efficacy of azathioprine in the treatment of chronic active Crohn 's disease is well established . However , this drug has a long onset of action . Methotrexate has also been shown to be effective in chronic active Crohn 's disease . The aim of this study was to evaluate the efficacy and safety of methotrexate in comparison with azathioprine , and to establish whether methotrexate has a shorter onset of action in this setting . METHODS Patients with chronic active Crohn 's disease were 
    Output:
    