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: Objectives : This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo . The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score ( based on erythrocyte sedimentation rates ; DAS28 ( ESR ) ) for the abatacept vs placebo groups at day 197 . Methods : Patients with rheumatoid arthritis ( RA ) and an inadequate response to methotrexate ( MTX )  were r and omised 3:3:2 to abatacept ( ∼10 mg/kg every 4 weeks , n = 156 ) , infliximab ( 3 mg/kg every 8 weeks , n = 165 ) , or placebo ( every 4 weeks , n = 110 ) and background MTX .  Safety and efficacy were assessed throughout the study . Results : Similar patient demographics and clinical characteristics were present at baseline between groups , with mean scores of ∼1.7 for HAQ-DI and 6.8 for DAS28 ( ESR ) . At 6 months , mean changes in DAS28 ( ESR ) were significantly greater for abatacept vs placebo ( –2.53 vs –1.48 , p<0.001 ) and infliximab vs placebo ( –2.25 vs –1.48 , p<0.001 ) . For abatacept vs infliximab treatment at day 365 , reductions in the DAS28 ( ESR ) were –2.88 vs –2.25 . At day 365 , the following response rates were observed for abatacept and infliximab , respectively : American College of Rheumatology ( ACR ) 20 , 72.4 and 55.8 % ; ACR 50 , 45.5 and 36.4 % ; ACR 70 , 26.3 and 20.6 % ; low disease activity score ( LDAS ) , 35.3 and 22.4 % ; DAS28-defined remission , 18.7 and 12.2 % ; good European League Against Rheumatism ( EULAR ) responses , 32.0 and 18.5 % ; and Health Assessment Question naire Disability Index ( HAQ-DI ) , 57.7 and 52.7 % . Mean changes in physical component summary ( PCS ) were 9.5 and 7.6 , and mental component summary ( MCS ) were 6.0 and 4.0 , for abatacept and infliximab , respectively . Over 1 year , adverse events ( AEs ) ( 89.1 vs 93.3 % ) , serious AEs ( SAEs ) ( 9.6 vs 18.2 % ) , serious infections ( 1.9 vs 8.5 % ) and discontinuations due to AEs ( 3.2 vs 7.3 % ) and SAEs ( 2.6 vs 3.6 % ) were lower with abatacept than infliximab . Conclusions : In this study , abatacept and infliximab ( 3 mg/kg every 8 weeks ) demonstrated similar efficacy . Overall , abatacept had a relatively more acceptable safety and tolerability profile , with fewer SAEs , serious infections , acute infusional events and discontinuations due to AEs than the infliximab group . Trial registration number : NCT00095147 OBJECTIVE To vali date the European League Against Rheumatism ( EULAR ) , the American College of Rheumatology ( ACR ) , and the World Health Organization (WHO)/International League Against Rheumatism ( ILAR ) response criteria for rheumatoid arthritis ( RA ) . METHODS EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up . In a trial comparing hydroxychloroquine and sulfasalazine , we studied construct ( radiographic progression ) , criterion ( functional capacity ) , and discriminant validity . RESULTS EULAR response criteria had good construct , criterion , and discriminant validity , ACR and WHO/ILAR criteria showed only good criterion validity . CONCLUSION EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA BACKGROUND Effective new therapies are needed for rheumatoid arthritis . Current therapies target the products of activated macrophages ; however , T cells also have an important role in rheumatoid arthritis . A fusion protein -- cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis . CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells , blocking the engagement of CD28 on T cells and preventing T-cell activation . A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis . METHODS We r and omly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig  per kilogram of body weight ( 105 patients ) , 10 mg of CTLA4Ig per kilogram ( 115 patients ) , or placebo  ( 119 patients ) for six months . All patients also received methotrexate therapy during the study . The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology ( ACR ) , which define the response according to its extent : 20 percent ( ACR 20 ) , 50 percent ( ACR 50 ) , or 70 percent ( ACR 70 ) . Additional end points included measures of the health-related quality of life . RESULTS Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo ( 60 percent vs. 35 percent , P<0.001 ) . Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group . The group given 10 mg of CTLA4Ig per kilogram had clinical ly meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey . CTLA4Ig was well tolerated , with an overall safety profile similar to that of placebo . CONCLUSIONS In patients with active rheumatoid arthritis who were receiving methotrexate  , treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life . CTLA4Ig is a promising new therapy for rheumatoid arthritis & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies OBJECTIVE Rheumatoid arthritis ( RA ) patients who have inadequate response to anti-tumour necrosis factor ( TNF ) therapy  currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio . Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population . The current study sought to demonstrate the efficacy of abatacept on quality of life ( QoL ) for RA patients with inadequate response to anti-TNF therapy . METHODS Patients were entered into a double-blind , placebo-controlled , multicentre r and omized clinical trial , with 258 patients r and omized to abatacept + disease-modifying anti-rheumatic drugs ( DMARDs ) and 133 patients r and omized to placebo + DMARDS . The QoL was measured with the Short Form Health Survey ( SF-36 ) , Health Assessment Question naire ( HAQ ) and fatigue visual analogue scale , and was analysed with basic ( ANOVA , chi-square ) and multigroup growth curve techniques to assess differential change over time . RESULTS Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices , as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores . Improvement rate was faster for abatacept than for placebo on the QoL measures , and the improvements from abatacept related to normal levels of QoL on many domains . CONCLUSION Clinical ly relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly , the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient 's life within a few weeks , even when the patient previously failed anti-TNF therapy OBJECTIVE T cells are involved in the pathogenesis of rheumatoid arthritis ( RA ) . In animal models of autoimmune diseases , blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation . To date , the effect of costimulatory blockade in patients with RA is unknown . The goal of this multicenter , multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent . METHODS CTLA-4Ig , LEA29Y ( 0.5 , 2 , or 10 mg/kg ) , or placebo was administered intravenously to 214 patients with RA . Patients received 4 infusions of study medication , on days 1 , 15 , 29 , and 57 , and were evaluated on day 85 . The primary end point was the proportion of patients meeting the American College of Rheumatology 20 % improvement criteria ( ACR20 ) . All patients were monitored for treatment safety and tolerability . RESULTS CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels . Peri-infusional adverse events were carefully monitored , and showed similar incidence across all dose groups with the exception of headaches , which were slightly more frequent in the 2 treatment groups . The incidence of discontinuations due to worsening of RA was 19 % , 12 % , and 9 % at 0.5 , 2 , and 10 mg/kg , respectively , in the CTLA-4Ig-treated patients and 3 % , 3 % , and 6 % at 0.5 , 2 , and 10 mg/kg , respectively , in the LEA29Y-treated patients ( versus 31 % in the placebo group ) . ACR20 responses on day 85 had increased in a dose-dependent manner ( 23 % , 44 % , and 53 % of CTLA-4Ig-treated patients and 34 % , 45 % , and 61 % of LEA29Y-treated patients at 0.5 , 2.0 , and 10 mg/kg , respectively , versus 31 % of placebo-treated patients ) . CONCLUSION Both of the costimulatory blocking molecules studied were generally safe and well tolerated . As compared with placebo , both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA Objective : To evaluate the responsiveness of patient reported outcomes ( PROs ) , including fatigue , sleep , activity limitation , and quality of life , in patients with rheumatoid arthritis ( RA ) . Methods : Data were considered from a r and omised controlled trial comparing  abatacept ( n = 258 )  with placebo ( n = 133 ) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy ( ATTAIN study ) . PROs assessed included SF-36 , activity limitation , fatigue , and sleep . For each outcome the treatment difference , relative per cent improvement , st and ardised response mean ( SRM ) , and relative efficiency for assessing an outcome ’s ability to detect a treatment effect relative to tender joint count ( TJC ) were calculated . A relative efficiency >  
    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: Objectives : This double-blind trial evaluated the efficacy and safety of abatacept or infliximab vs placebo . The primary objective of this study was to evaluate the mean change from baseline in Disease Activity Score ( based on erythrocyte sedimentation rates ; DAS28 ( ESR ) ) for the abatacept vs placebo groups at day 197 . Methods : Patients with rheumatoid arthritis ( RA ) and an inadequate response to methotrexate ( MTX )  were r and omised 3:3:2 to abatacept ( ∼10 mg/kg every 4 weeks , n = 156 ) , infliximab ( 3 mg/kg every 8 weeks , n = 165 ) , or placebo ( every 4 weeks , n = 110 ) and background MTX .  Safety and efficacy were assessed throughout the study . Results : Similar patient demographics and clinical characteristics were present at baseline between groups , with mean scores of ∼1.7 for HAQ-DI and 6.8 for DAS28 ( ESR ) . At 6 months , mean changes in DAS28 ( ESR ) were significantly greater for abatacept vs placebo ( –2.53 vs –1.48 , p<0.001 ) and infliximab vs placebo ( –2.25 vs –1.48 , p<0.001 ) . For abatacept vs infliximab treatment at day 365 , reductions in the DAS28 ( ESR ) were –2.88 vs –2.25 . At day 365 , the following response rates were observed for abatacept and infliximab , respectively : American College of Rheumatology ( ACR ) 20 , 72.4 and 55.8 % ; ACR 50 , 45.5 and 36.4 % ; ACR 70 , 26.3 and 20.6 % ; low disease activity score ( LDAS ) , 35.3 and 22.4 % ; DAS28-defined remission , 18.7 and 12.2 % ; good European League Against Rheumatism ( EULAR ) responses , 32.0 and 18.5 % ; and Health Assessment Question naire Disability Index ( HAQ-DI ) , 57.7 and 52.7 % . Mean changes in physical component summary ( PCS ) were 9.5 and 7.6 , and mental component summary ( MCS ) were 6.0 and 4.0 , for abatacept and infliximab , respectively . Over 1 year , adverse events ( AEs ) ( 89.1 vs 93.3 % ) , serious AEs ( SAEs ) ( 9.6 vs 18.2 % ) , serious infections ( 1.9 vs 8.5 % ) and discontinuations due to AEs ( 3.2 vs 7.3 % ) and SAEs ( 2.6 vs 3.6 % ) were lower with abatacept than infliximab . Conclusions : In this study , abatacept and infliximab ( 3 mg/kg every 8 weeks ) demonstrated similar efficacy . Overall , abatacept had a relatively more acceptable safety and tolerability profile , with fewer SAEs , serious infections , acute infusional events and discontinuations due to AEs than the infliximab group . Trial registration number : NCT00095147 OBJECTIVE To vali date the European League Against Rheumatism ( EULAR ) , the American College of Rheumatology ( ACR ) , and the World Health Organization (WHO)/International League Against Rheumatism ( ILAR ) response criteria for rheumatoid arthritis ( RA ) . METHODS EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up . In a trial comparing hydroxychloroquine and sulfasalazine , we studied construct ( radiographic progression ) , criterion ( functional capacity ) , and discriminant validity . RESULTS EULAR response criteria had good construct , criterion , and discriminant validity , ACR and WHO/ILAR criteria showed only good criterion validity . CONCLUSION EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA BACKGROUND Effective new therapies are needed for rheumatoid arthritis . Current therapies target the products of activated macrophages ; however , T cells also have an important role in rheumatoid arthritis . A fusion protein -- cytotoxic T-lymphocyte-associated antigen 4-IgG1 (CTLA4Ig)--is the first in a new class of drugs known as costimulation blockers being evaluated for the treatment of rheumatoid arthritis . CTLA4Ig binds to CD80 and CD86 on antigen-presenting cells , blocking the engagement of CD28 on T cells and preventing T-cell activation . A preliminary study showed that CTLA4Ig may be effective for the treatment of rheumatoid arthritis . METHODS We r and omly assigned patients with active rheumatoid arthritis despite methotrexate therapy to receive 2 mg of CTLA4Ig  per kilogram of body weight ( 105 patients ) , 10 mg of CTLA4Ig per kilogram ( 115 patients ) , or placebo  ( 119 patients ) for six months . All patients also received methotrexate therapy during the study . The clinical response was assessed at six months with use of the criteria of the American College of Rheumatology ( ACR ) , which define the response according to its extent : 20 percent ( ACR 20 ) , 50 percent ( ACR 50 ) , or 70 percent ( ACR 70 ) . Additional end points included measures of the health-related quality of life . RESULTS Patients treated with 10 mg of CTLA4Ig per kilogram were more likely to have an ACR 20 than were patients who received placebo ( 60 percent vs. 35 percent , P<0.001 ) . Significantly higher rates of ACR 50 and ACR 70 responses were seen in both CTLA4Ig groups than in the placebo group . The group given 10 mg of CTLA4Ig per kilogram had clinical ly meaningful and statistically significant improvements in all eight subscales of the Medical Outcomes 36-Item Short-Form General Health Survey . CTLA4Ig was well tolerated , with an overall safety profile similar to that of placebo . CONCLUSIONS In patients with active rheumatoid arthritis who were receiving methotrexate  , treatment with CTLA4Ig significantly improved the signs and symptoms of rheumatoid arthritis and the health-related quality of life . CTLA4Ig is a promising new therapy for rheumatoid arthritis & NA ;  Pain intensity is frequently measured on an 11‐point pain intensity numerical rating scale ( PI‐NRS ) , where 0=no pain and 10=worst possible pain . However , it is difficult to interpret the clinical importance of changes from baseline on this scale ( such as a 1‐ or 2‐point change ) . To date , there are no data driven estimates for clinical ly important differences in pain intensity scales used for chronic pain studies . We have estimated a clinical ly important difference on this scale by relating it to global assessment s of change in multiple studies of chronic pain . Data on 2724 subjects from 10 recently completed placebo‐controlled clinical trials of pregabalin in diabetic neuropathy , postherpetic neuralgia , chronic low back pain , fibromyalgia , and osteoarthritis were used . The studies had similar design s and measurement instruments , including the PI‐NRS , collected in a daily diary , and the st and ard seven‐point patient global impression of change ( PGIC ) , collected at the endpoint . The changes in the PI‐NRS from baseline to the endpoint were compared to the PGIC for each subject . Categories of ‘ much improved ’ and ‘ very much improved ’ were used as determinants of a clinical ly important difference and the relationship to the PI‐NRS was explored using graphs , box plots , and sensitivity/specificity analyses . A consistent relationship between the change in PI‐NRS and the PGIC was demonstrated regardless of study , disease type , age , sex , study result , or treatment group . On average , a reduction of approximately two points or a reduction of approximately 30 % in the PI‐NRS represented a clinical ly important difference . The relationship between percent change and the PGIC was also consistent regardless of baseline pain , while higher baseline scores required larger raw changes to represent a clinical ly important difference . The application of these results to future studies may provide a st and ard definition of clinical ly important improvement in clinical trials of chronic pain therapies . Use of a st and ard outcome across chronic pain studies would greatly enhance the comparability , validity , and clinical applicability of these studies OBJECTIVE Rheumatoid arthritis ( RA ) patients who have inadequate response to anti-tumour necrosis factor ( TNF ) therapy  currently have treatment options that are limited and less than optimal in their risk-to-benefit ratio . Abatacept provides a new generation of RA medications that has previously been demonstrated to have positive clinical outcomes with this population . The current study sought to demonstrate the efficacy of abatacept on quality of life ( QoL ) for RA patients with inadequate response to anti-TNF therapy . METHODS Patients were entered into a double-blind , placebo-controlled , multicentre r and omized clinical trial , with 258 patients r and omized to abatacept + disease-modifying anti-rheumatic drugs ( DMARDs ) and 133 patients r and omized to placebo + DMARDS . The QoL was measured with the Short Form Health Survey ( SF-36 ) , Health Assessment Question naire ( HAQ ) and fatigue visual analogue scale , and was analysed with basic ( ANOVA , chi-square ) and multigroup growth curve techniques to assess differential change over time . RESULTS Treatment group QoL improved significantly more than placebo on the HAQ and fatigue indices , as well as seven of the eight SF-36 scales and SF-36 physical and mental summary scores . Improvement rate was faster for abatacept than for placebo on the QoL measures , and the improvements from abatacept related to normal levels of QoL on many domains . CONCLUSION Clinical ly relevant benefits of abatacept over placebo are discussed regarding improving QoL. Importantly , the larger rate of change for abatacept over placebo provides clinicians with a medication that can lead to meaningful changes in a patient 's life within a few weeks , even when the patient previously failed anti-TNF therapy OBJECTIVE T cells are involved in the pathogenesis of rheumatoid arthritis ( RA ) . In animal models of autoimmune diseases , blockade of costimulatory molecules on antigen-presenting cells has been demonstrated to be effective in preventing or treating this disease by preventing T cell activation . To date , the effect of costimulatory blockade in patients with RA is unknown . The goal of this multicenter , multinational study was to determine the safety and preliminary efficacy of costimulatory blockade using CTLA-4Ig and LEA29Y in RA patients who have been treated unsuccessfully with at least 1 disease-modifying agent . METHODS CTLA-4Ig , LEA29Y ( 0.5 , 2 , or 10 mg/kg ) , or placebo was administered intravenously to 214 patients with RA . Patients received 4 infusions of study medication , on days 1 , 15 , 29 , and 57 , and were evaluated on day 85 . The primary end point was the proportion of patients meeting the American College of Rheumatology 20 % improvement criteria ( ACR20 ) . All patients were monitored for treatment safety and tolerability . RESULTS CTLA-4Ig and LEA29Y infusions were well tolerated at all dose levels . Peri-infusional adverse events were carefully monitored , and showed similar incidence across all dose groups with the exception of headaches , which were slightly more frequent in the 2 treatment groups . The incidence of discontinuations due to worsening of RA was 19 % , 12 % , and 9 % at 0.5 , 2 , and 10 mg/kg , respectively , in the CTLA-4Ig-treated patients and 3 % , 3 % , and 6 % at 0.5 , 2 , and 10 mg/kg , respectively , in the LEA29Y-treated patients ( versus 31 % in the placebo group ) . ACR20 responses on day 85 had increased in a dose-dependent manner ( 23 % , 44 % , and 53 % of CTLA-4Ig-treated patients and 34 % , 45 % , and 61 % of LEA29Y-treated patients at 0.5 , 2.0 , and 10 mg/kg , respectively , versus 31 % of placebo-treated patients ) . CONCLUSION Both of the costimulatory blocking molecules studied were generally safe and well tolerated . As compared with placebo , both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA Objective : To evaluate the responsiveness of patient reported outcomes ( PROs ) , including fatigue , sleep , activity limitation , and quality of life , in patients with rheumatoid arthritis ( RA ) . Methods : Data were considered from a r and omised controlled trial comparing  abatacept ( n = 258 )  with placebo ( n = 133 ) on a background of DMARD treatment in RA patients who were inadequate responders to anti-TNF therapy ( ATTAIN study ) . PROs assessed included SF-36 , activity limitation , fatigue , and sleep . For each outcome the treatment difference , relative per cent improvement , st and ardised response mean ( SRM ) , and relative efficiency for assessing an outcome ’s ability to detect a treatment effect relative to tender joint count ( TJC ) were calculated . A relative efficiency >  
    Output:
    