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: OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns Objective To compare the value that rheumatologists across Europe attach to patients ' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis . Methods In a discrete choice experiment , European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity . Treatments differed in five attributes : efficacy ( improvement and achieved state on disease activity ) , safety ( probability of serious adverse events ) , patient 's preference ( level of agreement ) , medication costs and cost-effectiveness ( incremental cost-effectiveness ratio ( ICER ) ) . A Bayesian efficient design defined 14 choice sets , and a r and om parameter logit model was used to estimate relative preferences for rheumatologists across countries . Cluster analyses and latent class models were applied to underst and preference patterns across countries and among individual rheumatologists . Results Responses of 559 rheumatologists from 12 European countries were included in the analysis ( 49 % females , mean age 48 years ) . In all countries , efficacy dominated treatment decisions followed by economic considerations and patients ’ preferences . Across countries , rheumatologists avoided selecting a treatment that patients disliked . Latent class models revealed four respondent profiles : one traded off all attributes except safety , and the remaining three classes disregarded ICER . Among individual rheumatologists , 57 % disregarded ICER and these were more likely from Italy , Romania , Portugal or France , whereas 43 % disregarded uncommon/rare side effects and were more likely from Belgium , Germany , Hungary , the Netherl and s , Norway , Spain , Sweden or UK . Conclusions Overall , European rheumatologists are willing to trade between treatment efficacy , patients ' treatment preferences and economic considerations . However , the degree of trade-off differs between countries and among individuals Objectives To evaluate the efficacy and safety of adalimumab+methotrexate ( MTX ) in Japanese patients with early rheumatoid arthritis ( RA ) who had not previously received MTX or biologics . Methods This r and omised , double-blind , placebo-controlled , multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA ( ≤2-year duration ) . The primary endpoint was inhibition of radiographic progression ( change ( Δ ) from baseline in modified total Sharp score ( mTSS ) ) at week 26 . Results A total of 171 patients received  adalimumab+MTX ( mean dose , 6.2±0.8 mg/week ) and 163 patients  received MTX alone ( mean dose , 6.6±0.6 mg/week , p<0.001 ) . The mean RA duration was 0.3 years and 315 ( 94.3 % ) had high disease activity ( DAS28>5.1 ) . Adalimumab+MTX  significantly inhibited radiographic progression at week 26 versus MTX alone ( ΔmTSS , 1.5±6.1 vs 2.4±3.2 , respectively ; p<0.001 ) . Significantly more patients in the adalimumab+MTX group ( 62.0 % ) did not show radiographic progression ( ΔmTSS≤0.5 ) versus the MTX alone group ( 35.4 % ; p<0.001 ) . Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission , using various definitions , at 26 weeks versus MTX alone . Combination therapy was well tolerated , and no new safety signals were observed . Conclusions Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity Objective Early treatment of patients with rheumatoid arthritis ( RA ) with combination treatment starting with methotrexate , sulfasalazine , hydroxychloroquine and prednisolone ( FIN-RACo strategy ) is superior to monotherapy . A study was undertaken to determine whether infliximab ( INFL ) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome . Methods 99 patients with early untreated active RA were enrolled in an investigator-initiated , r and omised , double-blind , multicentre , parallel-group trial . Primary outcomes were remission and radiological changes at 2 years . All patients started with FIN-RACo . In addition , they were r and omised to receive INFL or placebo ( Pla ) from weeks 4 to 26 . Results At 24 months , 66 % and 53 % , respectively , of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology ( ACR ) criteria ( p=0.19 ) , 26 % and 10 % were in sustained modified ACR remission ( p=0.042 ) and 82 % in both groups were in remission by 28-joint disease activity score ( not significant ) . Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4 , respectively ( p=0.0058 ) . Conclusions Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen . Adding INFL for the first 6 months delays radiological progression Objective To compare the efficacy of etanercept ( ETN ) and methotrexate ( MTX ) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis . Methods In a 78-week multicentre r and omised placebo-controlled superiority trial , 110 DMARD-naïve patients with early clinical synovitis ( ≥1 tender and swollen joint , and within 3 months of diagnosis ) and either rheumatoid factor , anticitrullinated protein antibodies or shared epitope positive were r and omised 1:1 to receive MTX+ETN or MTX+placebo ( PBO ) for 52 weeks . Injections ( ETN or PBO ) were stopped in all patients at week 52 . In those with no tender or swollen joints ( NTSJ ) for > 26 weeks , injections were stopped early . If patients had NTSJ > 12 weeks after stopping the injections , MTX was weaned . The primary endpoint was NTSJ at week 52 . Results No statistically significant difference was seen for the primary endpoint ( NTSJ at week 52 ( 32.5 % vs 28.1 % [ adjusted OR 1.32 ( 0.56 to 3.09 ) , p=0.522 ] ) in the MTX+ETN and MTX+PBO groups , respectively ) . The secondary endpoints did not differ between groups at week 52 or 78 . Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 ( 38.5 % vs 9.2 % , adjusted OR 8.87 ( 2.53 to 31.17 ) , p=0.001 ) and week 12 ( 65.1 % vs 43.8 % , adjusted OR 2.49 ( 1.12 to 5.54 ) , p=0.026 ) . Conclusions In this group of patients with early inflammatory arthritis , almost a third had no tender , swollen joints after 1 year . MTX+ETN was not superior to MTX monotherapy in achieving this outcome . Clinical responses , however , including DAS28-CRP<2.6 , were achieved earlier with MTX+ETN combination therapy . Trial registration number The EMPIRE trial is registered on the following trial registries : Eudract-2005 - 005467 - 29 ; IS RCT N 55428162 ( http://www.controlled-trials.com/IS RCT N55428162/EMPIRE ) . The full trial protocol can be obtained from the corresponding author HighlightsEarly rheumatoid arthritis patients have increased levels of soluble CD83 in plasma . The release of soluble CD83 is independent of TNF‐&agr;.In rheumatoid arthritis sCD83 levels are higher in synovial fluid than in plasma . The level of soluble CD83 in plasma does not correlate with disease activity . CD83 is mainly expressed intracellularly in a variety of different cell types . Abstract Rheumatoid arthritis ( RA ) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases . In RA the levels of soluble CD83 ( sCD83 ) are elevated in synovial fluid , however little is known about CD83 expression and regulation in RA . Therefore , we studied how CD83 is expressed in RA and further evaluated the effect of anti‐TNF‐&agr ; therapy hereon . Early RA patients were r and omized to conventional disease modifying anti‐rheumatic drugs with or without additional anti‐TNF‐&agr ; therapy .  Rheumatoid arthritis patients had increased levels of sCD83 in plasma compared with healthy volunteers . The increase in sCD83 plasma levels were unaffected by anti‐TNF‐&agr ; therapy . In chronic RA patients the levels of sCD83 were higher in synovial fluid than in plasma , and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid . Finally , confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group of cells with diverse morphology including both antigen‐presenting cells and non‐antigen‐presenting cells . Our findings demonstrate that early‐stage RA patients have elevated levels of sCD83 in plasma and that anti‐TNF‐&agr ; treatment has no effect on the sCD83 plasma level . This suggest that in RA patients sCD83 regulation is beyond control of BACKGROUND Tumor necrosis factor ( TNF ) is an important mediator of cachexia , and its blockade prevents catabolism in animal models . However , little evidence shows that anti-TNF therapy is effective in treating cachexia in humans . OBJECTIVE The main aim of this study was to investigate the effect of etanercept , a synthetic soluble TNF receptor , on body composition in patients with early rheumatoid arthritis ( RA ) . DESIGN Twenty-six patients were r and omly assigned to 24 wk of treatment with  etanercept or methotrexate ; the latter is the first-line therapy for RA . Body composition , physical function , disease activity , systemic inflammation , and the circulating insulin-like growth factor ( IGF ) system were measured at baseline ( week 0 ) and at follow-up ( weeks 12 and 24 ) . Twelve patients in each treatment group ( 
    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: OBJECTIVE To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis ( RA ) . METHODS MTX-naive patients with RA ( n = 637 ) were r and omized to receive placebo plus MTX ( group 1 ) , golimumab 100 mg plus placebo ( group 2 ) , golimumab 50 mg plus MTX ( group 3 ) , or golimumab 100 mg plus MTX ( group 4 ) . Subcutaneous injections of golimumab or placebo were administered every 4 weeks . The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week . The primary end point , the proportion of patients meeting the American College of Rheumatology 50 % improvement criteria ( achieving an ACR50 response ) at week 24 , required significant differences between groups 3 and 4 combined ( combined group ) versus group 1 and significant differences in a pairwise comparison ( group 3 or group 4 versus group 1 ) . RESULTS An intent-to-treat ( ITT ) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 ( 38.4 % and 29.4 % , respectively ; P=0.053 ) , while a post hoc modified ITT analysis ( excluding 3 untreated patients ) of the ACR50 response showed statistically significant differences between the combined group and group 1 ( 38.5 % versus 29.4 % ; P=0.049 ) and between group 3 ( 40.5 % ; P=0.038 ) but not group 4 ( 36.5 % ; P=0.177 ) and group 1 . Group 2 was noninferior to group 1 for the ACR50 response at week 24 ( 33.1 % ; 95 % confidence interval lower bound -5.2 % ; predefined delta value for noninferiority -10 % ) . The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters , including response/remission according to the Disease Activity Score in 28 joints . Serious adverse events occurred in 7 % , 3 % , 6 % , and 6 % of patients in groups 1 , 2 , 3 , and 4 , respectively . CONCLUSION Although the primary end point was not met , the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than , and the efficacy of golimumab alone is similar to , the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients , with no unexpected safety concerns Objective To compare the value that rheumatologists across Europe attach to patients ' preferences and economic aspects when choosing treatments for patients with rheumatoid arthritis . Methods In a discrete choice experiment , European rheumatologists chose between two hypothetical drug treatments for a patient with moderate disease activity . Treatments differed in five attributes : efficacy ( improvement and achieved state on disease activity ) , safety ( probability of serious adverse events ) , patient 's preference ( level of agreement ) , medication costs and cost-effectiveness ( incremental cost-effectiveness ratio ( ICER ) ) . A Bayesian efficient design defined 14 choice sets , and a r and om parameter logit model was used to estimate relative preferences for rheumatologists across countries . Cluster analyses and latent class models were applied to underst and preference patterns across countries and among individual rheumatologists . Results Responses of 559 rheumatologists from 12 European countries were included in the analysis ( 49 % females , mean age 48 years ) . In all countries , efficacy dominated treatment decisions followed by economic considerations and patients ’ preferences . Across countries , rheumatologists avoided selecting a treatment that patients disliked . Latent class models revealed four respondent profiles : one traded off all attributes except safety , and the remaining three classes disregarded ICER . Among individual rheumatologists , 57 % disregarded ICER and these were more likely from Italy , Romania , Portugal or France , whereas 43 % disregarded uncommon/rare side effects and were more likely from Belgium , Germany , Hungary , the Netherl and s , Norway , Spain , Sweden or UK . Conclusions Overall , European rheumatologists are willing to trade between treatment efficacy , patients ' treatment preferences and economic considerations . However , the degree of trade-off differs between countries and among individuals Objectives To evaluate the efficacy and safety of adalimumab+methotrexate ( MTX ) in Japanese patients with early rheumatoid arthritis ( RA ) who had not previously received MTX or biologics . Methods This r and omised , double-blind , placebo-controlled , multicentre study evaluated adalimumab 40 mg every other week+MTX 6–8 mg every week versus MTX 6–8 mg every week alone for 26 weeks in patients with RA ( ≤2-year duration ) . The primary endpoint was inhibition of radiographic progression ( change ( Δ ) from baseline in modified total Sharp score ( mTSS ) ) at week 26 . Results A total of 171 patients received  adalimumab+MTX ( mean dose , 6.2±0.8 mg/week ) and 163 patients  received MTX alone ( mean dose , 6.6±0.6 mg/week , p<0.001 ) . The mean RA duration was 0.3 years and 315 ( 94.3 % ) had high disease activity ( DAS28>5.1 ) . Adalimumab+MTX  significantly inhibited radiographic progression at week 26 versus MTX alone ( ΔmTSS , 1.5±6.1 vs 2.4±3.2 , respectively ; p<0.001 ) . Significantly more patients in the adalimumab+MTX group ( 62.0 % ) did not show radiographic progression ( ΔmTSS≤0.5 ) versus the MTX alone group ( 35.4 % ; p<0.001 ) . Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission , using various definitions , at 26 weeks versus MTX alone . Combination therapy was well tolerated , and no new safety signals were observed . Conclusions Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity Objective Early treatment of patients with rheumatoid arthritis ( RA ) with combination treatment starting with methotrexate , sulfasalazine , hydroxychloroquine and prednisolone ( FIN-RACo strategy ) is superior to monotherapy . A study was undertaken to determine whether infliximab ( INFL ) added to intensified FIN-RACo treatment for the initial 6 months improves the 2-year outcome . Methods 99 patients with early untreated active RA were enrolled in an investigator-initiated , r and omised , double-blind , multicentre , parallel-group trial . Primary outcomes were remission and radiological changes at 2 years . All patients started with FIN-RACo . In addition , they were r and omised to receive INFL or placebo ( Pla ) from weeks 4 to 26 . Results At 24 months , 66 % and 53 % , respectively , of the patients in the FIN-RACo+INFL and FIN-RACo+Pla groups were in remission according to the modified American College of Rheumatology ( ACR ) criteria ( p=0.19 ) , 26 % and 10 % were in sustained modified ACR remission ( p=0.042 ) and 82 % in both groups were in remission by 28-joint disease activity score ( not significant ) . Mean changes in the total Sharp-van der Heijde score were 0.2 and 1.4 , respectively ( p=0.0058 ) . Conclusions Most patients with early active RA achieve clinical remission and develop negligible joint damage with the intensified FIN-RACo regimen . Adding INFL for the first 6 months delays radiological progression Objective To compare the efficacy of etanercept ( ETN ) and methotrexate ( MTX ) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis . Methods In a 78-week multicentre r and omised placebo-controlled superiority trial , 110 DMARD-naïve patients with early clinical synovitis ( ≥1 tender and swollen joint , and within 3 months of diagnosis ) and either rheumatoid factor , anticitrullinated protein antibodies or shared epitope positive were r and omised 1:1 to receive MTX+ETN or MTX+placebo ( PBO ) for 52 weeks . Injections ( ETN or PBO ) were stopped in all patients at week 52 . In those with no tender or swollen joints ( NTSJ ) for > 26 weeks , injections were stopped early . If patients had NTSJ > 12 weeks after stopping the injections , MTX was weaned . The primary endpoint was NTSJ at week 52 . Results No statistically significant difference was seen for the primary endpoint ( NTSJ at week 52 ( 32.5 % vs 28.1 % [ adjusted OR 1.32 ( 0.56 to 3.09 ) , p=0.522 ] ) in the MTX+ETN and MTX+PBO groups , respectively ) . The secondary endpoints did not differ between groups at week 52 or 78 . Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 ( 38.5 % vs 9.2 % , adjusted OR 8.87 ( 2.53 to 31.17 ) , p=0.001 ) and week 12 ( 65.1 % vs 43.8 % , adjusted OR 2.49 ( 1.12 to 5.54 ) , p=0.026 ) . Conclusions In this group of patients with early inflammatory arthritis , almost a third had no tender , swollen joints after 1 year . MTX+ETN was not superior to MTX monotherapy in achieving this outcome . Clinical responses , however , including DAS28-CRP<2.6 , were achieved earlier with MTX+ETN combination therapy . Trial registration number The EMPIRE trial is registered on the following trial registries : Eudract-2005 - 005467 - 29 ; IS RCT N 55428162 ( http://www.controlled-trials.com/IS RCT N55428162/EMPIRE ) . The full trial protocol can be obtained from the corresponding author HighlightsEarly rheumatoid arthritis patients have increased levels of soluble CD83 in plasma . The release of soluble CD83 is independent of TNF‐&agr;.In rheumatoid arthritis sCD83 levels are higher in synovial fluid than in plasma . The level of soluble CD83 in plasma does not correlate with disease activity . CD83 is mainly expressed intracellularly in a variety of different cell types . Abstract Rheumatoid arthritis ( RA ) is an autoimmune disease which may lead to severe disabilities due to structural joint damage and extraarticular manifestations The dendritic cell marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with autoimmune diseases . In RA the levels of soluble CD83 ( sCD83 ) are elevated in synovial fluid , however little is known about CD83 expression and regulation in RA . Therefore , we studied how CD83 is expressed in RA and further evaluated the effect of anti‐TNF‐&agr ; therapy hereon . Early RA patients were r and omized to conventional disease modifying anti‐rheumatic drugs with or without additional anti‐TNF‐&agr ; therapy .  Rheumatoid arthritis patients had increased levels of sCD83 in plasma compared with healthy volunteers . The increase in sCD83 plasma levels were unaffected by anti‐TNF‐&agr ; therapy . In chronic RA patients the levels of sCD83 were higher in synovial fluid than in plasma , and only a limited amount of membrane bound CD83 expression was detected on the surface of cells from peripheral blood and synovial fluid . Finally , confocal microscopy of RA synovial membranes revealed that CD83 was mainly localized intracellularly in a group of cells with diverse morphology including both antigen‐presenting cells and non‐antigen‐presenting cells . Our findings demonstrate that early‐stage RA patients have elevated levels of sCD83 in plasma and that anti‐TNF‐&agr ; treatment has no effect on the sCD83 plasma level . This suggest that in RA patients sCD83 regulation is beyond control of BACKGROUND Tumor necrosis factor ( TNF ) is an important mediator of cachexia , and its blockade prevents catabolism in animal models . However , little evidence shows that anti-TNF therapy is effective in treating cachexia in humans . OBJECTIVE The main aim of this study was to investigate the effect of etanercept , a synthetic soluble TNF receptor , on body composition in patients with early rheumatoid arthritis ( RA ) . DESIGN Twenty-six patients were r and omly assigned to 24 wk of treatment with  etanercept or methotrexate ; the latter is the first-line therapy for RA . Body composition , physical function , disease activity , systemic inflammation , and the circulating insulin-like growth factor ( IGF ) system were measured at baseline ( week 0 ) and at follow-up ( weeks 12 and 24 ) . Twelve patients in each treatment group ( 
    Output:
    