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 : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimumab 40 mg every other week and 83 % who received 40 mg weekly were in remission at week 56 , v 44 % for placebo ( p<0.05 ) . In all , 204 patients entered the open-label arm . Of these , 93 ( 46 % ) were in clinical remission at week 56 . Adalimumab was generally well-tolerated in all patients . Conclusions : Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn ’s disease naive to anti-TNF treatment BACKGROUND & AIMS We assessed the relationship between antibodies to infliximab ( ATI ) and the loss of response postinfliximab , infusion reactions and , in a r and omized trial , investigated whether intravenous hydrocortisone premedication can reduce ATI . METHODS Initially , we prospect ively evaluated clinical response , adverse events , and ATI levels in 53 consecutive patients with Crohn 's disease who received 199 infliximab ( 5 mg/kg ) infusions . Subsequently , 80 patients with Crohn 's disease were r and omized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions . The primary endpoint was reduction in median ATI levels at week 16 . Analysis was by intention to treat . RESULTS Nineteen of our initial 53 patients ( 36 % ) developed ATI , including all 7 patients with serious infusion reactions ( median ATI level , 19.6 microg/mL ) . Eleven of 15 patients ( 73 % ) who lost their initial response were ATI positive compared with none of 21 continuous responders , ( 8.9 vs. 0.7 microg/mL , P < 0.0001 ) . Administering a second infusion within 8 weeks of the first ( OR , 0.13 ; 95 % CI , 0.03 - 0.5 ; P = 0.0007 ) or concurrent immunosuppressants ( OR , 0.19 ; 95 % CI , 0.04 - 1.03 ; P = 0.007 ) significantly reduced ATI formation . In the placebo-controlled trial , ATI levels were lower at week 16 among hydrocortisone-treated patients ( 1.6 vs. 3.4 microg/mL , P = 0.02 ) , and 26 % of hydrocortisone-treated patients developed ATI compared with 42 % of placebo-treated patients , P = 0.06 . CONCLUSIONS Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level . Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation . Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions Introduction : Crohn ’s disease ( CD ) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract . Adalimumab ( ADA ) is a subcutaneously administered , recombinant , fully human , IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha , thus modulating its biologic functions and its proinflammatory effects . Aims : To review the available data on ADA in CD for biological properties , efficacy , and safety . Methods : Electronic search es were conducted using the Pubmed and SCOPUS data bases from the earliest records to April 2008 . The search terms used were “ adalimumab ” , “ anti-TNF ” , “ TNF-alpha ” , “ biologicals ” , “ inflammatory bowel disease ” , and “ Crohn ’s disease ” . Reference lists of all relevant articles were search ed for further studies . Results : Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD , both in anti-TNF-naïve patients and in subjects who lost their response and /or became intolerant to infliximab ( IFX ) . ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure ( although no specific r and omized trials are available ) . No concomitant immunosuppressors seem to be necessary . Side effects appear similar to IFX , while site-injection reactions are frequent and specific . Data on immunogenicity and its clinical impact are uncertain . Conclusions : ADA appears to be effective in inducing and maintain clinical remission in CD , including patients not manageable with IFX . Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD . The impact on clinical management or on re sources should be more studied OBJECTIVE Infliximab , an anti-tumor necrosis factor alpha ( anti-TNFalpha ) antibody , is effective in the treatment of several immunoinflammatory diseases . However , many patients experience primary or secondary response failure , suggesting that individualization of treatment regimens may be beneficial . This study was undertaken to investigate whether serologic monitoring of infliximab  bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability . METHODS To avoid the use of solid-phase assays , two radioimmunoassays were developed : one for measurement of levels of anti-infliximab antibody , and a functional one for measurement of TNFalpha binding due to infliximab . Sera from 106 r and omly selected rheumatoid arthritis patients were tested within 6 months of therapy initiation , and associations between findings of serum assays and disease activity , infusion reactions , and treatment failure occurring within 18 months were assessed . RESULTS Trough serum infliximab levels after the first 2 intravenous infusions of infliximab at 3 mg/kg varied considerably between patients ( range 0 - 22 microg/ml ) . At this stage , only 13 % of the patients were anti-infliximab antibody positive . With subsequent infusions , the frequency of antibody positivity rose to 30 % and 44 % ( at 3 months and 6 months , respectively ) , accompanied by diminished trough levels of infliximab .  Indeed , low  infliximab levels at 1.5 months predicted antibody development and later treatment failure . There were highly significant correlations between high levels of antibodies and later dose increases , side effects , and cessation of therapy . High baseline disease activity , judged by C-reactive protein level and Disease Activity Score , was associated with low levels of  infliximab  at the early stage of treatment and later development of anti-infliximab antibodies . Cotreatment with methotrexate result ed in slightly reduced antibody levels after 6 months ; other disease-modifying antirheumatic drugs and prednisolone had no effect . CONCLUSION Development of anti-infliximab antibodies , heralded by low preinfusion serum infliximab levels , is associated with increased risk of infusion reaction and treatment failure . Early monitoring may help optimize dosing regimens for individual patients , diminish side effects , and prevent prolonged use of inadequate infliximab therapy Data from clinical trials suggest the efficacy of the chimeric tumor necrosis factor alpha monocl 
    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 : Adalimumab induced clinical remission after four weeks in patients with active Crohn ’s disease in the CLASSIC I trial . Objective : To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn ’s disease in a follow-on r and omised controlled trial ( CLASSIC II ) . Methods : In the preceding CLASSIC I trial , 299 patients with moderate to severe Crohn ’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg , 80 mg/40 mg , or 160 mg/80 mg , or placebo , at weeks 0 and 2 . In all , 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 ( week 4 of CLASSIC I ) and 2 ; 55 patients in remission at both weeks 0 and 4 were re-r and omised to adalimumab 40 mg every other week , 40 mg weekly , or placebo for 56 weeks . Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week . With non-response or flare , these patients could have their dosages increased to 40 mg weekly . Patients in the r and omised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly . The primary end point was maintenance of remission ( CDAI < 150 ) in r and omised patients through week 56 . Results : Of 55 patients r and omised at week 4 , 79 % who received adalimumab 40 mg every other week and 83 % who received 40 mg weekly were in remission at week 56 , v 44 % for placebo ( p<0.05 ) . In all , 204 patients entered the open-label arm . Of these , 93 ( 46 % ) were in clinical remission at week 56 . Adalimumab was generally well-tolerated in all patients . Conclusions : Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn ’s disease naive to anti-TNF treatment BACKGROUND & AIMS We assessed the relationship between antibodies to infliximab ( ATI ) and the loss of response postinfliximab , infusion reactions and , in a r and omized trial , investigated whether intravenous hydrocortisone premedication can reduce ATI . METHODS Initially , we prospect ively evaluated clinical response , adverse events , and ATI levels in 53 consecutive patients with Crohn 's disease who received 199 infliximab ( 5 mg/kg ) infusions . Subsequently , 80 patients with Crohn 's disease were r and omized to intravenous hydrocortisone 200 mg or placebo immediately before their first and subsequent infliximab infusions . The primary endpoint was reduction in median ATI levels at week 16 . Analysis was by intention to treat . RESULTS Nineteen of our initial 53 patients ( 36 % ) developed ATI , including all 7 patients with serious infusion reactions ( median ATI level , 19.6 microg/mL ) . Eleven of 15 patients ( 73 % ) who lost their initial response were ATI positive compared with none of 21 continuous responders , ( 8.9 vs. 0.7 microg/mL , P < 0.0001 ) . Administering a second infusion within 8 weeks of the first ( OR , 0.13 ; 95 % CI , 0.03 - 0.5 ; P = 0.0007 ) or concurrent immunosuppressants ( OR , 0.19 ; 95 % CI , 0.04 - 1.03 ; P = 0.007 ) significantly reduced ATI formation . In the placebo-controlled trial , ATI levels were lower at week 16 among hydrocortisone-treated patients ( 1.6 vs. 3.4 microg/mL , P = 0.02 ) , and 26 % of hydrocortisone-treated patients developed ATI compared with 42 % of placebo-treated patients , P = 0.06 . CONCLUSIONS Loss of initial response and infusion reactions post-infliximab is strongly related to ATI formation and level . Administering a second infusion within 8 weeks of the first and concurrent immunosuppressant therapy significantly reduce ATI formation . Intravenous hydrocortisone premedication significantly reduces ATI levels but does not eliminate ATI formation or infusion reactions Introduction : Crohn ’s disease ( CD ) is a chronic inflammatory bowel disease characterized by a relapsing-remitting course with trans-mural inflammation of potentially any section of the digestive tract . Adalimumab ( ADA ) is a subcutaneously administered , recombinant , fully human , IgG1 monoclonal antibody that binds with high affinity and specificity to human TNF-alpha , thus modulating its biologic functions and its proinflammatory effects . Aims : To review the available data on ADA in CD for biological properties , efficacy , and safety . Methods : Electronic search es were conducted using the Pubmed and SCOPUS data bases from the earliest records to April 2008 . The search terms used were “ adalimumab ” , “ anti-TNF ” , “ TNF-alpha ” , “ biologicals ” , “ inflammatory bowel disease ” , and “ Crohn ’s disease ” . Reference lists of all relevant articles were search ed for further studies . Results : Available studies suggest that ADA has the potential to induce and maintain clinical response and remission in moderate-severe CD , both in anti-TNF-naïve patients and in subjects who lost their response and /or became intolerant to infliximab ( IFX ) . ADA seems also effective in maintaining corticosteroid-free remission and obtaining complete fistula closure ( although no specific r and omized trials are available ) . No concomitant immunosuppressors seem to be necessary . Side effects appear similar to IFX , while site-injection reactions are frequent and specific . Data on immunogenicity and its clinical impact are uncertain . Conclusions : ADA appears to be effective in inducing and maintain clinical remission in CD , including patients not manageable with IFX . Successive clinical practice and further on going trials will confirm a positive role for ADA as a new anti-TNF treatment in CD . The impact on clinical management or on re sources should be more studied OBJECTIVE Infliximab , an anti-tumor necrosis factor alpha ( anti-TNFalpha ) antibody , is effective in the treatment of several immunoinflammatory diseases . However , many patients experience primary or secondary response failure , suggesting that individualization of treatment regimens may be beneficial . This study was undertaken to investigate whether serologic monitoring of infliximab  bioavailability and immunogenicity in individual patients would be useful in optimizing treatment regimens to improve efficacy and tolerability . METHODS To avoid the use of solid-phase assays , two radioimmunoassays were developed : one for measurement of levels of anti-infliximab antibody , and a functional one for measurement of TNFalpha binding due to infliximab . Sera from 106 r and omly selected rheumatoid arthritis patients were tested within 6 months of therapy initiation , and associations between findings of serum assays and disease activity , infusion reactions , and treatment failure occurring within 18 months were assessed . RESULTS Trough serum infliximab levels after the first 2 intravenous infusions of infliximab at 3 mg/kg varied considerably between patients ( range 0 - 22 microg/ml ) . At this stage , only 13 % of the patients were anti-infliximab antibody positive . With subsequent infusions , the frequency of antibody positivity rose to 30 % and 44 % ( at 3 months and 6 months , respectively ) , accompanied by diminished trough levels of infliximab .  Indeed , low  infliximab levels at 1.5 months predicted antibody development and later treatment failure . There were highly significant correlations between high levels of antibodies and later dose increases , side effects , and cessation of therapy . High baseline disease activity , judged by C-reactive protein level and Disease Activity Score , was associated with low levels of  infliximab  at the early stage of treatment and later development of anti-infliximab antibodies . Cotreatment with methotrexate result ed in slightly reduced antibody levels after 6 months ; other disease-modifying antirheumatic drugs and prednisolone had no effect . CONCLUSION Development of anti-infliximab antibodies , heralded by low preinfusion serum infliximab levels , is associated with increased risk of infusion reaction and treatment failure . Early monitoring may help optimize dosing regimens for individual patients , diminish side effects , and prevent prolonged use of inadequate infliximab therapy Data from clinical trials suggest the efficacy of the chimeric tumor necrosis factor alpha monocl 
    Output:
    