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 Objective The aim of this study was to assess the efficacy and safety of adalimumab ( ADA ) , a recombinant human monoclonal antibody against tumour necrosis factor α ( TNF ) , for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis . Methods This 8-week , multicentre , r and omised , double-blind , placebo-controlled study ( NCT00385736 ) , conducted at 94 centres in North America and Europe , enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and /or immunosuppressants . Under the original study protocol , 186 patients were r and omised ( 1:1 ) to subcutaneous treatment with ADA160/80 ( 160 mg at week 0 , 80 mg at week 2 , 40 mg at weeks 4 and 6 ) or placebo . Subsequently , at the request of European regulatory authorities , the protocol was amended to include a second induction group ( ADA80/40 : 80 mg at week 0 , 40 mg at weeks 2 , 4 and 6 ) . The primary efficacy endpoint was clinical remission ( Mayo score ≤2 with no individual subscore > 1 ) at week 8 , assessed in 390 patients r and omised ( 1:1:1 ) to ADA160/80 , ADA80/40 , or placebo . Safety was assessed in all enrolled patients . Patients , study site personnel , investigators , and the sponsor were blinded to treatment assignment . Results At week 8 , 18.5 % of patients in the ADA160/80 group ( p=0.031 vs placebo ) and 10.0 % in the ADA80/40 group ( p=0.833 vs placebo ) were in remission , compared with 9.2 % in the placebo group . Serious adverse events occurred in 7.6 % , 3.8 % and 4.0 % of patients in the placebo , ADA80/40 , and ADA160/80 groups , respectively . There were two malignancies in the placebo group , none in the ADA groups . There were no cases of tuberculosis and no deaths . Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and /or immunosuppressants . Clinical trial NCT00385736 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 BACKGROUND & AIMS Crohn 's disease commonly recurs after intestinal resection . We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn 's disease reduces postoperative recurrence . METHODS We r and omly assigned 24 patients with Crohn 's disease who had undergone ileocolonic resection to receive intravenous infliximab ( 5 mg/kg ) , administered within 4 weeks of surgery and continued for 1 year , or placebo . The primary end point was the proportion of patients with endoscopic recurrence at 1 year . Secondary end points were clinical recurrence and remission and histologic recurrence . RESULTS The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group ( 1 of 11 patients ; 9.1 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .0006 ) . There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group ( 8 of 10 ; 80.0 % ) compared with the placebo group ( 7 of 13 ; 53.8 % ) ( P = .38 ) . The histologic recurrence rate at 1 year was significantly lower in the infliximab group ( 3 of 11 patients ; 27.3 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .01 ) . The occurrence of adverse events was similar between the placebo and infliximab groups , and none occurred in the immediate postoperative period . CONCLUSIONS Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn 's disease BACKGROUND Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial . We assessed this risk in a prospect i ve observational cohort study . METHODS 19,486 patients with inflammatory bowel disease , of whom 11,759 ( 60.3 % ) had Crohn 's disease and 7727 ( 39.7 % ) had ulcerative colitis or unclassified inflammatory bowel disease , were enrolled in a nationwide French cohort by 680 gastroenterologists , who reported details of immunosuppressive therapy during the observation period , cases of cancer , and deaths . The risk of lymphoproliferative disorder was assessed according to thiopurine exposure . Median follow-up was 35 months ( IQR 29 - 40 ) . FINDINGS At baseline , 5867 ( 30.1 % ) of patients were receiving , 2809 ( 14.4 % ) had discontinued , and 10,810 ( 55.5 % ) had never received thiopurines . 23 new cases of lymphoproliferative disorder were diagnosed , consisting of one case of Hodgkin 's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder . The incidence rates of lymphoproliferative disorder were 0.90 per 1000 ( 95 % CI 0.50 - 1.49 ) patient-years in those receiving , 0.20/1000 ( 0.02 - 0.72 ) patient-years in those who had discontinued , and 0.26/1000 ( 0.10 - 0.57 ) patient-years in those who had never received thiopurines ( p=0.0054 ) . The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 ( 2.01 - 13.9 , p=0.0007 ) . Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease . INTERPRETATION Patients receiving thiopurines  for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders . FUNDING Programme Hospitalier de Recherche Clinique National ( AOM05157 ) , Association François Aupetit , Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris ( AP-HP ) , Ligue contre le Cancer , 
    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 Objective The aim of this study was to assess the efficacy and safety of adalimumab ( ADA ) , a recombinant human monoclonal antibody against tumour necrosis factor α ( TNF ) , for the induction of clinical remission in anti-TNF naïve patients with moderately to severely active ulcerative colitis . Methods This 8-week , multicentre , r and omised , double-blind , placebo-controlled study ( NCT00385736 ) , conducted at 94 centres in North America and Europe , enrolled ambulatory adult patients with Mayo score of ≥6 points and endoscopic subscore of ≥2 points despite treatment with corticosteroids and /or immunosuppressants . Under the original study protocol , 186 patients were r and omised ( 1:1 ) to subcutaneous treatment with ADA160/80 ( 160 mg at week 0 , 80 mg at week 2 , 40 mg at weeks 4 and 6 ) or placebo . Subsequently , at the request of European regulatory authorities , the protocol was amended to include a second induction group ( ADA80/40 : 80 mg at week 0 , 40 mg at weeks 2 , 4 and 6 ) . The primary efficacy endpoint was clinical remission ( Mayo score ≤2 with no individual subscore > 1 ) at week 8 , assessed in 390 patients r and omised ( 1:1:1 ) to ADA160/80 , ADA80/40 , or placebo . Safety was assessed in all enrolled patients . Patients , study site personnel , investigators , and the sponsor were blinded to treatment assignment . Results At week 8 , 18.5 % of patients in the ADA160/80 group ( p=0.031 vs placebo ) and 10.0 % in the ADA80/40 group ( p=0.833 vs placebo ) were in remission , compared with 9.2 % in the placebo group . Serious adverse events occurred in 7.6 % , 3.8 % and 4.0 % of patients in the placebo , ADA80/40 , and ADA160/80 groups , respectively . There were two malignancies in the placebo group , none in the ADA groups . There were no cases of tuberculosis and no deaths . Conclusions ADA160/80 was safe and effective for induction of clinical remission in patients with moderately to severely active ulcerative colitis failing treatment with corticosteroids and /or immunosuppressants . Clinical trial NCT00385736 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 BACKGROUND & AIMS Crohn 's disease commonly recurs after intestinal resection . We evaluated whether the administration of infliximab after resective intestinal surgery for Crohn 's disease reduces postoperative recurrence . METHODS We r and omly assigned 24 patients with Crohn 's disease who had undergone ileocolonic resection to receive intravenous infliximab ( 5 mg/kg ) , administered within 4 weeks of surgery and continued for 1 year , or placebo . The primary end point was the proportion of patients with endoscopic recurrence at 1 year . Secondary end points were clinical recurrence and remission and histologic recurrence . RESULTS The rate of endoscopic recurrence at 1 year was significantly lower in the infliximab group ( 1 of 11 patients ; 9.1 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .0006 ) . There was a nonsignificant higher proportion of patients in clinical remission in the infliximab group ( 8 of 10 ; 80.0 % ) compared with the placebo group ( 7 of 13 ; 53.8 % ) ( P = .38 ) . The histologic recurrence rate at 1 year was significantly lower in the infliximab group ( 3 of 11 patients ; 27.3 % ) compared with the placebo group ( 11 of 13 patients ; 84.6 % ) ( P = .01 ) . The occurrence of adverse events was similar between the placebo and infliximab groups , and none occurred in the immediate postoperative period . CONCLUSIONS Administration of infliximab after intestinal resective surgery was effective at preventing endoscopic and histologic recurrence of Crohn 's disease BACKGROUND Reports of an increased risk of lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease are controversial . We assessed this risk in a prospect i ve observational cohort study . METHODS 19,486 patients with inflammatory bowel disease , of whom 11,759 ( 60.3 % ) had Crohn 's disease and 7727 ( 39.7 % ) had ulcerative colitis or unclassified inflammatory bowel disease , were enrolled in a nationwide French cohort by 680 gastroenterologists , who reported details of immunosuppressive therapy during the observation period , cases of cancer , and deaths . The risk of lymphoproliferative disorder was assessed according to thiopurine exposure . Median follow-up was 35 months ( IQR 29 - 40 ) . FINDINGS At baseline , 5867 ( 30.1 % ) of patients were receiving , 2809 ( 14.4 % ) had discontinued , and 10,810 ( 55.5 % ) had never received thiopurines . 23 new cases of lymphoproliferative disorder were diagnosed , consisting of one case of Hodgkin 's lymphoma and 22 cases of non-Hodgkin lymphoproliferative disorder . The incidence rates of lymphoproliferative disorder were 0.90 per 1000 ( 95 % CI 0.50 - 1.49 ) patient-years in those receiving , 0.20/1000 ( 0.02 - 0.72 ) patient-years in those who had discontinued , and 0.26/1000 ( 0.10 - 0.57 ) patient-years in those who had never received thiopurines ( p=0.0054 ) . The multivariate-adjusted hazard ratio of lymphoproliferative disorder between patients receiving thiopurines and those who had never received the drugs was 5.28 ( 2.01 - 13.9 , p=0.0007 ) . Most cases associated with thiopurine exposure matched the pathological range of post-transplant disease . INTERPRETATION Patients receiving thiopurines  for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders . FUNDING Programme Hospitalier de Recherche Clinique National ( AOM05157 ) , Association François Aupetit , Délégation Inter-régionale de la Recherche clinique Ile de France-Assistance Publique Hôpitaux de Paris ( AP-HP ) , Ligue contre le Cancer , 
    Output:
    