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 & AIMS Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis . The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a r and omized , double-blind multicenter trial . METHODS Patients with active ulcerative colitis who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study .  Methotrexate ( 12.5 mg ) or placebo was added to their treatment once weekly for 9 months . RESULTS Sixty-seven patients were included ( methotrexate , 30 patients , placebo , 37 patients ) . The proportion of patients entering first remission  ( methotrexate , 46.7 % ; placebo , 48.6 % ) , the time to reach first remission  ( methotrexate , 4.1 + /- 1.9 months ; placebo , 3.4 + /- 1.7 months ) , as well as the proportions of patients having a relapse after first remission  ( methotrexate , 64.3 % ; placebo , 44.4 % ) were not significantly different between the two groups . The mean Mayo Clinic score , the mean monthly steroid dose , and the proportion of abnormal laboratory results during the study were also similar . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis BACKGROUND : Previous studies suggested that methotrexate has beneficial effects in patients with Crohn 's disease . We report our experience with this agent in patients with chronic active Crohn 's disease who previously failed to improve with conventional treatment , including azathioprine  in most cases . METHODS : Between June 1988 and June 1992 , 39 patients with refractory Crohn 's disease were treated with methotrexate .  In patients with active disease , clinical remission was defined by a Harvey‐Bradshaw index of less than 4 . For patients also taking corticosteroids , the date s of remission and complete steroid withdrawal were recorded . For patients who achieved clinical remission , and those in clinical remission when methotrexate was started , the relapse rate on methotrexate therapy was noted . RESULTS : In the 37 patients with active disease at methotrexate initiation , the probability of remission was 72 % at 3 months . The probability of remission and steroid withdrawal was 42 % at 12 months . In patients on clinical remission , the probability of relapse  on methotrexate was 58 % at 12 months . Twenty‐two patients experienced side‐effects , but these only warranted methotrexate discontinuation in four cases . CONCLUSIONS : Methotrexate appears effective in most patients with refractory Crohn 's disease and its short‐term toxicity is acceptable , but the long‐term benefit seems more limited BACKGROUND & AIMS Parenteral methotrexate is an effective treatment for patients with Crohn 's disease , but has never been adequately evaluated in patients with ulcerative colitis ( UC ) . We conducted a r and omized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC . METHODS We performed a double-blind , placebo-controlled trial to evaluate the efficacy of parenteral methotrexate ( 25 mg/wk ) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013 . Patients were given prednisone ( 10 to 40 mg/d ) when the study began and were r and omly assigned to groups ( 1:1 ) given placebo or methotrexate ( intramuscularly or subcutaneously , 25 mg weekly ) for 24 weeks . The primary end point was steroid-free remission ( defined as a Mayo score ≤2 with no item > 1 and complete withdrawal of steroids ) at week 16 . Secondary endpoints included clinical remission ( defined as a Mayo clinical subscore ≤2 with no item > 1 ) and endoscopic healing without steroids at weeks 16 and /or 24 , remission without steroids at week 24 , and remission at both weeks 16 and 24 . RESULTS Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate ( 31.7 % ) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1 % ( 95 % confidence interval [ CI ] : -4.0 % to 28.1 % ; P = .15 ) . The proportion of patients in steroid-free clinical remission at week 16 was 41.7 % in the methotrexate group and 23.5 % in the placebo group , for a difference of 18.1 % ( 95 % CI : 1.1 % to 35.2 % ; P = .04 ) . The proportions of patients with steroid-free endoscopic healing at week 16 were 35 % in the methotrexate group and 25.5 % in the placebo group -- a difference of 9.5 % ( 95 % CI : -7.5 % to 26.5 % ; P = .28 ) . No differences were observed in other secondary end points . More patients receiving placebo discontinued the study because of adverse events ( 47.1 % ) , mostly caused by UC , than patients receiving methotrexate ( 26.7 % ; P = .03 ) . A higher proportion of patients in the methotrexate group had nausea and vomiting ( 21.7 % ) than in the placebo group ( 3.9 % ; P = .006 ) . CONCLUSIONS In a r and omized controlled trial , parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC . However , methotrexate induced clinical remission without steroids in a significantly larger percentage of patients , result ing in fewer withdrawals from therapy due to active UC . Clinical Trials.gov ID NCT00498589 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 The purpose of this study was to evaluate the efficacy and safety of low-dose weekly , oral methotrexate in patients with steroid-dependent or steroid-refractory inflammatory bowel disease ( IBD ) .  Oral methotrexate was given weekly at 15 mg/week . The primary criterion of response was based on steroid withdrawal . Of the 10 patients with Crohn 's disease , daily prednisone dosage dropped from a mean of 37±9.6 mg to 8.3±2.1 mg/day ( P<0.02 ) ; two had a complete withdrawal and four a partial response ( < 7.5 mg/day ) . In the eight patients with ulcerative colitis , daily prednisone dose dropped from a mean of 26.3±3.2 mg/day to 12.7±2.0 mg/day ( P<0.001 ) ; three had a partial response . Adverse effects  due to methotrexate were mild in both groups . We conclude that oral methotrexate may be useful and reasonably safe as a steroid-sparing agent in patients with refractory IBD 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 Biomarkers of intestinal inflammation , such as faecal calprotectin and C-reactive protein , have been recommended for monitoring patients with Crohn 's disease , but whether their use in treatment decisions improves outcomes is unknown . We aim ed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn 's disease who were managed with a tight control algorithm  , using clinical symptoms and biomarkers , versus patients managed with a clinical management algorithm .  METHODS CALM was an open-label , r and omised , controlled phase 3 study , done in 22 countries at 74 hospitals and outpatient centres , which evaluated adult patients ( aged 18 - 75 years ) with active endoscopic Crohn 's disease ( Crohn 's Disease Endoscopic Index of Severity [ CDEIS ] > 6 ; sum of CDEIS subscores of > 6 in one or more segments with ulcers ) , a Crohn 's Disease Activity Index ( CDAI ) of 150 - 450 depending on dose of prednisone at baseline , and no previous use of immunomodulators or biologics . Patients were r and omly assigned at a 1:1 ratio to tight control or clinical management groups , stratified by smoking status ( yes or no ) , weight ( < 70 kg or ≥70 kg ) , and disease duration ( ≤2 years or > 2 years ) after 8 weeks of prednisone induction therapy , or earlier if they had active disease . In both groups , treatment was escalated in a stepwise manner , from no treatment , to adalimumab induction followed by adalimumab every other week , adalimumab every week , and lastly to both weekly adalimumab and daily azathioprine . This escalation was based on meeting treatment failure criteria , which differed between groups ( tight control group before and after r and om assignment : faecal calprotectin ≥250 μg/g , C-reactive protein ≥5mg/L , CDAI ≥150 , or prednisone use in the previous week ; clinical management group before r and om assignment : CDAI decrease of < 70 points compared with baseline or CDAI > 200 ; clinical management group after r and om assignment : CDAI decrease of < 100 points compared with baseline or CDAI ≥200 , or prednisone use in the previous week ) . De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met . The primary endpoint was mucosal healing ( CDEIS < 4 ) with absence of deep ulcers 48 weeks after r and omisation . Primary and safety analyses were done in the intention-to-treat population . This trial has been completed , and is registered with Clinical Trials.gov , number NCT01235689 . FINDINGS Between Feb 11 , 2011 , and Nov  
    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 & AIMS Uncontrolled studies have suggested that methotrexate may be effective in patients with active ulcerative colitis . The aim of this study was to evaluate the effectiveness of oral methotrexate in chronic steroid-dependent ulcerative colitis in a r and omized , double-blind multicenter trial . METHODS Patients with active ulcerative colitis who have received steroids and /or immunosuppressives for at least 4 months during the preceding 12 months with a current Mayo Clinic score of > or = 7 were included in the study .  Methotrexate ( 12.5 mg ) or placebo was added to their treatment once weekly for 9 months . RESULTS Sixty-seven patients were included ( methotrexate , 30 patients , placebo , 37 patients ) . The proportion of patients entering first remission  ( methotrexate , 46.7 % ; placebo , 48.6 % ) , the time to reach first remission  ( methotrexate , 4.1 + /- 1.9 months ; placebo , 3.4 + /- 1.7 months ) , as well as the proportions of patients having a relapse after first remission  ( methotrexate , 64.3 % ; placebo , 44.4 % ) were not significantly different between the two groups . The mean Mayo Clinic score , the mean monthly steroid dose , and the proportion of abnormal laboratory results during the study were also similar . CONCLUSIONS Methotrexate at a weekly oral dose of 12.5 mg was not found to be better than placebo in the induction or maintenance of remission in patients with chronic active ulcerative colitis BACKGROUND : Previous studies suggested that methotrexate has beneficial effects in patients with Crohn 's disease . We report our experience with this agent in patients with chronic active Crohn 's disease who previously failed to improve with conventional treatment , including azathioprine  in most cases . METHODS : Between June 1988 and June 1992 , 39 patients with refractory Crohn 's disease were treated with methotrexate .  In patients with active disease , clinical remission was defined by a Harvey‐Bradshaw index of less than 4 . For patients also taking corticosteroids , the date s of remission and complete steroid withdrawal were recorded . For patients who achieved clinical remission , and those in clinical remission when methotrexate was started , the relapse rate on methotrexate therapy was noted . RESULTS : In the 37 patients with active disease at methotrexate initiation , the probability of remission was 72 % at 3 months . The probability of remission and steroid withdrawal was 42 % at 12 months . In patients on clinical remission , the probability of relapse  on methotrexate was 58 % at 12 months . Twenty‐two patients experienced side‐effects , but these only warranted methotrexate discontinuation in four cases . CONCLUSIONS : Methotrexate appears effective in most patients with refractory Crohn 's disease and its short‐term toxicity is acceptable , but the long‐term benefit seems more limited BACKGROUND & AIMS Parenteral methotrexate is an effective treatment for patients with Crohn 's disease , but has never been adequately evaluated in patients with ulcerative colitis ( UC ) . We conducted a r and omized controlled trial to determine its safety and efficacy in patients with steroid-dependent UC . METHODS We performed a double-blind , placebo-controlled trial to evaluate the efficacy of parenteral methotrexate ( 25 mg/wk ) in 111 patients with corticosteroid-dependent UC at 26 medical centers in Europe from 2007 through 2013 . Patients were given prednisone ( 10 to 40 mg/d ) when the study began and were r and omly assigned to groups ( 1:1 ) given placebo or methotrexate ( intramuscularly or subcutaneously , 25 mg weekly ) for 24 weeks . The primary end point was steroid-free remission ( defined as a Mayo score ≤2 with no item > 1 and complete withdrawal of steroids ) at week 16 . Secondary endpoints included clinical remission ( defined as a Mayo clinical subscore ≤2 with no item > 1 ) and endoscopic healing without steroids at weeks 16 and /or 24 , remission without steroids at week 24 , and remission at both weeks 16 and 24 . RESULTS Steroid-free remission at week 16 was achieved by 19 of 60 patients given methotrexate ( 31.7 % ) and 10 of 51 patients given placebo (19.6%)--a difference of 12.1 % ( 95 % confidence interval [ CI ] : -4.0 % to 28.1 % ; P = .15 ) . The proportion of patients in steroid-free clinical remission at week 16 was 41.7 % in the methotrexate group and 23.5 % in the placebo group , for a difference of 18.1 % ( 95 % CI : 1.1 % to 35.2 % ; P = .04 ) . The proportions of patients with steroid-free endoscopic healing at week 16 were 35 % in the methotrexate group and 25.5 % in the placebo group -- a difference of 9.5 % ( 95 % CI : -7.5 % to 26.5 % ; P = .28 ) . No differences were observed in other secondary end points . More patients receiving placebo discontinued the study because of adverse events ( 47.1 % ) , mostly caused by UC , than patients receiving methotrexate ( 26.7 % ; P = .03 ) . A higher proportion of patients in the methotrexate group had nausea and vomiting ( 21.7 % ) than in the placebo group ( 3.9 % ; P = .006 ) . CONCLUSIONS In a r and omized controlled trial , parenteral methotrexate was not superior to placebo for induction of steroid-free remission in patients with UC . However , methotrexate induced clinical remission without steroids in a significantly larger percentage of patients , result ing in fewer withdrawals from therapy due to active UC . Clinical Trials.gov ID NCT00498589 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 The purpose of this study was to evaluate the efficacy and safety of low-dose weekly , oral methotrexate in patients with steroid-dependent or steroid-refractory inflammatory bowel disease ( IBD ) .  Oral methotrexate was given weekly at 15 mg/week . The primary criterion of response was based on steroid withdrawal . Of the 10 patients with Crohn 's disease , daily prednisone dosage dropped from a mean of 37±9.6 mg to 8.3±2.1 mg/day ( P<0.02 ) ; two had a complete withdrawal and four a partial response ( < 7.5 mg/day ) . In the eight patients with ulcerative colitis , daily prednisone dose dropped from a mean of 26.3±3.2 mg/day to 12.7±2.0 mg/day ( P<0.001 ) ; three had a partial response . Adverse effects  due to methotrexate were mild in both groups . We conclude that oral methotrexate may be useful and reasonably safe as a steroid-sparing agent in patients with refractory IBD 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 Biomarkers of intestinal inflammation , such as faecal calprotectin and C-reactive protein , have been recommended for monitoring patients with Crohn 's disease , but whether their use in treatment decisions improves outcomes is unknown . We aim ed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn 's disease who were managed with a tight control algorithm  , using clinical symptoms and biomarkers , versus patients managed with a clinical management algorithm .  METHODS CALM was an open-label , r and omised , controlled phase 3 study , done in 22 countries at 74 hospitals and outpatient centres , which evaluated adult patients ( aged 18 - 75 years ) with active endoscopic Crohn 's disease ( Crohn 's Disease Endoscopic Index of Severity [ CDEIS ] > 6 ; sum of CDEIS subscores of > 6 in one or more segments with ulcers ) , a Crohn 's Disease Activity Index ( CDAI ) of 150 - 450 depending on dose of prednisone at baseline , and no previous use of immunomodulators or biologics . Patients were r and omly assigned at a 1:1 ratio to tight control or clinical management groups , stratified by smoking status ( yes or no ) , weight ( < 70 kg or ≥70 kg ) , and disease duration ( ≤2 years or > 2 years ) after 8 weeks of prednisone induction therapy , or earlier if they had active disease . In both groups , treatment was escalated in a stepwise manner , from no treatment , to adalimumab induction followed by adalimumab every other week , adalimumab every week , and lastly to both weekly adalimumab and daily azathioprine . This escalation was based on meeting treatment failure criteria , which differed between groups ( tight control group before and after r and om assignment : faecal calprotectin ≥250 μg/g , C-reactive protein ≥5mg/L , CDAI ≥150 , or prednisone use in the previous week ; clinical management group before r and om assignment : CDAI decrease of < 70 points compared with baseline or CDAI > 200 ; clinical management group after r and om assignment : CDAI decrease of < 100 points compared with baseline or CDAI ≥200 , or prednisone use in the previous week ) . De-escalation was possible for patients receiving weekly adalimumab and azathioprine or weekly adalimumab alone if failure criteria were not met . The primary endpoint was mucosal healing ( CDEIS < 4 ) with absence of deep ulcers 48 weeks after r and omisation . Primary and safety analyses were done in the intention-to-treat population . This trial has been completed , and is registered with Clinical Trials.gov , number NCT01235689 . FINDINGS Between Feb 11 , 2011 , and Nov  
    Output:
    