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 efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis ( RA ) . METHODS At the start of their initial treatment with a disease-modifying antirheumatic drug ( DMARD ) , patients with early ( duration < or = 1 year ) active RA were r and omly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years . Radiographs of the h and s and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde . Remission was defined as a Disease Activity Score in 28 joints of < 2.6 . Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years . RESULTS Of the 250 patients included , 242 completed the study and 225 had radiographs available both at baseline and at 2 years . At 2 years , the median and interquartile range ( IQR ) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group ( 1.8 [ IQR 0.5 - 6.0 ] versus 3.5 [ IQR 0.5 - 10 ] ; P = 0.019 ) . In the prednisolone group , there were fewer newly eroded joints per patient after 2 years ( median 0.5 [ IQR 0 - 2 ] versus 1.25 [ IQR 0 - 3.25 ] ; P = 0.007 ) . In the prednisolone group , 25.9 % of patients had radiographic progression beyond the smallest detectable difference compared with 39.3 % of patients in the no-prednisolone group ( P = 0.033 ) . At 2 years , 55.5 % of patients in the prednisolone group had achieved disease remission , compared with 32.8 % of patients in the no-prednisolone group ( P = 0.0005 ) . There were few adverse events that led to withdrawal . Bone loss during the 2-year study was similar in the 2 treatment groups . CONCLUSION Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA , provided a high remission rate , and was well tolerated . Therefore , the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA Erosions and cartilage destruction are nearly universal features in peripheral joints that have been chronically affected by rheumatoid arthritis .  Scoring methods to measure the extent of these abnormalities in h and s and wrists have been developed and have been thoroughly tested in several studies to establish their reproducibility . In this study , we utilized one of these scoring methods to examine the progression of radiologic damage as related to duration of disease . Two hundred ninety-two patients from 3 different participating centers in the Arthritis , Rheumatism , and Aging Medical Information System were included . Six hundred fifty films of the h and s and wrists , obtained from 210 patients , were scored for  erosions and joint space narrowing . The average annual rate of progression of the total radiologic score , which sums erosion and joint space abnormalities and has a maximum possible score of 314 , was approximately 4 units per year over the first 25 years after onset ; this progression was more rapid in the earlier years of disease and slightly slower in the later years . Data were insufficient to accurately determine the progression rate in disease of more than 25 years duration OBJECTIVE To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis ( RA ) treated with methotrexate ( MTX )  versus those treated with infliximab plus MTX . METHODS Patients who had not previously been treated with MTX with active RA were r and omly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . Radiographic joint damage was assessed using the modified Sharp/van der Heijde score ( SHS ) . The relationship between disease activity measures at baseline and week 14 , as well as those averaged over time , were examined in relation to the change in SHS from baseline through week 54 . RESULTS C-reactive protein ( CRP ) levels , erythrocyte sedimentation rate ( ESR ) , and swollen joint count were associated with greater joint damage progression in the MTX-only group , while none of these parameters was associated with progression in the infliximab plus MTX group . Mean changes in SHS among patients in the highest CRP ( > or = 3 mg/dl ) and ESR ( > or = 52 mm/hour ) tertiles in the MTX-only group were 5.62 and 5.89 , respectively , compared with 0.73 and 1.12 in the infliximab plus MTX group ( P < 0.001 ) . Patients with greater joint damage at baseline ( SHS > or = 10.5 ) showed less progression with infliximab plus MTX compared with MTX alone ( -0.39 versus 4.11 ; P < 0.001 ) . Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab . CONCLUSION High CRP level , high ESR , or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone , while little radiographic progression was seen in patients receiving both MTX and infliximab , regardless of the abnormal levels of these traditional predictors CONTEXT Men with low bone mineral density ( BMD ) were treated with denosumab . OBJECTIVE Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment . DESIGN , SUBJECTS , AND INTERVENTION This was a placebo-controlled , phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD . MAIN OUTCOME MEASURE The primary endpoint was the percent change from baseline in lumbar spine ( LS ) BMD at month 12 . RESULTS Of the 242 r and omized subjects ( mean age 65 yr ) , 228 ( 94.2 % ) completed 1 yr of denosumab therapy . After 12 months , denosumab result ed in BMD increases of 5.7 % at the LS , 2.4 % at the total hip , 2.1 % at the femoral neck , 3.1 % at the trochanter , and 0.6 % at the one third radius ( adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo ) . Sensitivity analyses done by controlling for baseline covariates ( such as baseline testosterone levels , BMD T-scores , and 10-yr osteoporotic fracture risk ) demonstrated that the results of the primary endpoint were robust . Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations . Treatment with denosumab significantly reduced serum CTX levels at d 15 ( adjusted P < 0.0001 ) . The incidence of adverse events was similar between groups . CONCLUSIONS One year of denosumab  therapy in men with low BMD was well tolerated and result ed in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed OBJECTIVE To determine the potential for additive or synergistic effects of combination therapy with the selective anti-tumor necrosis factor alpha agent etanercept and the anti-interleukin-1 agent anakinra . METHODS Two hundred forty-four patients in whom rheumatoid arthritis ( RA ) was active despite methotrexate therapy were treated with subcutaneous etanercept only ( 25 mg twice weekly ) , full-dosage etanercept ( 25 mg twice weekly ) plus anakinra ( 100 mg/day ) , or half-dosage etanercept ( 25 mg once weekly ) plus anakinra ( 100 mg/day ) for 6 months in a double-blind study at 41 centers in the US . Patients had never previously received anticytokine therapy . Patient response was measured with the American College of Rheumatology ( ACR ) core set criteria , a health-related quality -of-life question naire , and the Disease Activity Score . Safety was assessed by the number of adverse events and clinical laboratory values . Plasma concentrations of both agents and antibody formation against both agents were also assessed . RESULTS Combination therapy with etanercept plus anakinra provided no treatment benefit over etanercept alone , regardless of the regimen , but was associated with an increased safety risk . Thirty-one percent of the patients treated with full-dosage etanercept plus anakinra achieved an ACR 50 % response , compared with 41 % of the patients treated with etanercept only . This result was not statistically significant ( P = 0.914 ) . The incidence of serious infections ( 0 % for etanercept alone , 3.7 - 7.4 % for combination therapy ) , injection-site reactions , and neutropenia was increased with combination therapy . Combination therapy had no effect on the pharmacokinetics or immunogenicity of either agent . CONCLUSION Combination therapy with etanercept and anakinra provides no added benefit and an increased risk compared with etanercept alone and is not recommended for the treatment of patients with RA OBJECTIVE Bisphosphonates inhibit osteoclast activity , which is central to the development of bone damage in rheumatoid arthritis ( RA ) . The aim of this study was to assess whether treatment with zoledronic acid , compared with placebo , could achieve a > or = 50 % reduction in the development of new erosions on magnetic resonance imaging ( MRI ) in patients with early RA . METHODS In this proof-of-concept study , 39 patients with early RA and clinical synovitis of the h and /wrist were r and omized to receive infusions with either zoledronic acid ( 5 mg ) or placebo , administered at baseline and week 13 . Patients in both groups received methotrexate ( MTX ) at a dosage of 7.5 - 20 mg/week . MRI and plain radiography were performed at baseline and week 26 . RESULTS At week 26 , the mean + /- SD change in MRI h and and wrist erosions was 61 % lower in the zoledronic acid group compared with the placebo group ( 0.9 + /- 1.63 versus 2.3 + /- 3.09 ; P = 0.176 ) . The mean + /- SD increase in the number of h and and wrist bones with erosions was 0.3 + /- 0.75 for zoledronic acid compared with 1.4 + /- 1.77 for placebo ( P = 0.029 ) . The proportion of patients in whom new MRI-visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group ( 33 % versus 58 % ; P = 0.121 ) . The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group ( P = 0.677 ) . The safety profile of zoledronic acid was similar to that of placebo . CONCLUSION The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA , as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone OBJECTIVES To study the effect of oral clodronate on structural damage and bone metabolism in rheumatoid arthritis ( RA ) . METHODS In this 2-year proof-of-concept study , sixty patients with at least moderately active RA were r and omised to receive anti-rheumatic therapy alone or together with oral clodronate 1600 mg daily . Radiographs of h and s and feet and serum sample s for bone biomarkers were studied at baseline and at 24 months . RESULTS At 24 months , progression of radiographic joint damage was similar in the 2 groups . Clodronate suppressed carboxyterminal cross-linked peptide of type I collagen ( p=0.03 ) and aminoterminal propeptide of type I procollagen ( p=0.01 ) . Eight patients ( 27 % ) withdrew from clodronate therapy due to adverse drug reactions . CONCLUSIONS Oral clodronate did not retard the focal bone damage in RA despite its beneficial effect on overall bone metabolism , as judged by the decrease in the reference bone biomarkers Objectives To report results of subgroup analyses of bone mineral density ( BMD ) and bone turnover markers from a r and omised , double-blind , placebo-controlled , phase II study of denosumab , an investigational RANKL inhibitor , in patients with rheumatoid arthritis ( RA ) concurrently receiving treatment with bisphosphonates or glucocorticoids . Methods Patients received subcutaneous placebo ( n=75 ) , denosumab 60 mg ( n=71 ) or denosumab 180 mg ( n=72 ) at baseline and 6 months . Assessment s included dual x-ray absorptiometry scans of the lumbar spine and hip , and determination of levels of serum type I C-telopeptide ( sCTx- 
    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 efficacy of low-dose prednisolone on joint damage and disease activity in patients with early rheumatoid arthritis ( RA ) . METHODS At the start of their initial treatment with a disease-modifying antirheumatic drug ( DMARD ) , patients with early ( duration < or = 1 year ) active RA were r and omly assigned to receive either 7.5 mg/day prednisolone or no prednisolone for 2 years . Radiographs of the h and s and feet were obtained at baseline and after 1 and 2 years and scored according to the Sharp score as modified by van der Heijde . Remission was defined as a Disease Activity Score in 28 joints of < 2.6 . Bone mineral density was measured by dual x-ray absorptiometry at baseline and after 2 years . RESULTS Of the 250 patients included , 242 completed the study and 225 had radiographs available both at baseline and at 2 years . At 2 years , the median and interquartile range ( IQR ) change in total Sharp score was lower in the prednisolone group than in the no-prednisolone group ( 1.8 [ IQR 0.5 - 6.0 ] versus 3.5 [ IQR 0.5 - 10 ] ; P = 0.019 ) . In the prednisolone group , there were fewer newly eroded joints per patient after 2 years ( median 0.5 [ IQR 0 - 2 ] versus 1.25 [ IQR 0 - 3.25 ] ; P = 0.007 ) . In the prednisolone group , 25.9 % of patients had radiographic progression beyond the smallest detectable difference compared with 39.3 % of patients in the no-prednisolone group ( P = 0.033 ) . At 2 years , 55.5 % of patients in the prednisolone group had achieved disease remission , compared with 32.8 % of patients in the no-prednisolone group ( P = 0.0005 ) . There were few adverse events that led to withdrawal . Bone loss during the 2-year study was similar in the 2 treatment groups . CONCLUSION Prednisolone at 7.5 mg/day added to the initial DMARD retarded the progression of radiographic damage after 2 years in patients with early RA , provided a high remission rate , and was well tolerated . Therefore , the data support the use of low-dose prednisolone as an adjunct to DMARDs in early active RA Erosions and cartilage destruction are nearly universal features in peripheral joints that have been chronically affected by rheumatoid arthritis .  Scoring methods to measure the extent of these abnormalities in h and s and wrists have been developed and have been thoroughly tested in several studies to establish their reproducibility . In this study , we utilized one of these scoring methods to examine the progression of radiologic damage as related to duration of disease . Two hundred ninety-two patients from 3 different participating centers in the Arthritis , Rheumatism , and Aging Medical Information System were included . Six hundred fifty films of the h and s and wrists , obtained from 210 patients , were scored for  erosions and joint space narrowing . The average annual rate of progression of the total radiologic score , which sums erosion and joint space abnormalities and has a maximum possible score of 314 , was approximately 4 units per year over the first 25 years after onset ; this progression was more rapid in the earlier years of disease and slightly slower in the later years . Data were insufficient to accurately determine the progression rate in disease of more than 25 years duration OBJECTIVE To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis ( RA ) treated with methotrexate ( MTX )  versus those treated with infliximab plus MTX . METHODS Patients who had not previously been treated with MTX with active RA were r and omly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0 , 2 , and 6 , and every 8 weeks thereafter through week 46 . Radiographic joint damage was assessed using the modified Sharp/van der Heijde score ( SHS ) . The relationship between disease activity measures at baseline and week 14 , as well as those averaged over time , were examined in relation to the change in SHS from baseline through week 54 . RESULTS C-reactive protein ( CRP ) levels , erythrocyte sedimentation rate ( ESR ) , and swollen joint count were associated with greater joint damage progression in the MTX-only group , while none of these parameters was associated with progression in the infliximab plus MTX group . Mean changes in SHS among patients in the highest CRP ( > or = 3 mg/dl ) and ESR ( > or = 52 mm/hour ) tertiles in the MTX-only group were 5.62 and 5.89 , respectively , compared with 0.73 and 1.12 in the infliximab plus MTX group ( P < 0.001 ) . Patients with greater joint damage at baseline ( SHS > or = 10.5 ) showed less progression with infliximab plus MTX compared with MTX alone ( -0.39 versus 4.11 ; P < 0.001 ) . Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab . CONCLUSION High CRP level , high ESR , or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone , while little radiographic progression was seen in patients receiving both MTX and infliximab , regardless of the abnormal levels of these traditional predictors CONTEXT Men with low bone mineral density ( BMD ) were treated with denosumab . OBJECTIVE Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment . DESIGN , SUBJECTS , AND INTERVENTION This was a placebo-controlled , phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD . MAIN OUTCOME MEASURE The primary endpoint was the percent change from baseline in lumbar spine ( LS ) BMD at month 12 . RESULTS Of the 242 r and omized subjects ( mean age 65 yr ) , 228 ( 94.2 % ) completed 1 yr of denosumab therapy . After 12 months , denosumab result ed in BMD increases of 5.7 % at the LS , 2.4 % at the total hip , 2.1 % at the femoral neck , 3.1 % at the trochanter , and 0.6 % at the one third radius ( adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo ) . Sensitivity analyses done by controlling for baseline covariates ( such as baseline testosterone levels , BMD T-scores , and 10-yr osteoporotic fracture risk ) demonstrated that the results of the primary endpoint were robust . Subgroup analyses indicate that treatment with denosumab was effective across a spectrum of clinical situations . Treatment with denosumab significantly reduced serum CTX levels at d 15 ( adjusted P < 0.0001 ) . The incidence of adverse events was similar between groups . CONCLUSIONS One year of denosumab  therapy in men with low BMD was well tolerated and result ed in a reduction in bone resorption and significant increases in BMD at all skeletal sites assessed OBJECTIVE To determine the potential for additive or synergistic effects of combination therapy with the selective anti-tumor necrosis factor alpha agent etanercept and the anti-interleukin-1 agent anakinra . METHODS Two hundred forty-four patients in whom rheumatoid arthritis ( RA ) was active despite methotrexate therapy were treated with subcutaneous etanercept only ( 25 mg twice weekly ) , full-dosage etanercept ( 25 mg twice weekly ) plus anakinra ( 100 mg/day ) , or half-dosage etanercept ( 25 mg once weekly ) plus anakinra ( 100 mg/day ) for 6 months in a double-blind study at 41 centers in the US . Patients had never previously received anticytokine therapy . Patient response was measured with the American College of Rheumatology ( ACR ) core set criteria , a health-related quality -of-life question naire , and the Disease Activity Score . Safety was assessed by the number of adverse events and clinical laboratory values . Plasma concentrations of both agents and antibody formation against both agents were also assessed . RESULTS Combination therapy with etanercept plus anakinra provided no treatment benefit over etanercept alone , regardless of the regimen , but was associated with an increased safety risk . Thirty-one percent of the patients treated with full-dosage etanercept plus anakinra achieved an ACR 50 % response , compared with 41 % of the patients treated with etanercept only . This result was not statistically significant ( P = 0.914 ) . The incidence of serious infections ( 0 % for etanercept alone , 3.7 - 7.4 % for combination therapy ) , injection-site reactions , and neutropenia was increased with combination therapy . Combination therapy had no effect on the pharmacokinetics or immunogenicity of either agent . CONCLUSION Combination therapy with etanercept and anakinra provides no added benefit and an increased risk compared with etanercept alone and is not recommended for the treatment of patients with RA OBJECTIVE Bisphosphonates inhibit osteoclast activity , which is central to the development of bone damage in rheumatoid arthritis ( RA ) . The aim of this study was to assess whether treatment with zoledronic acid , compared with placebo , could achieve a > or = 50 % reduction in the development of new erosions on magnetic resonance imaging ( MRI ) in patients with early RA . METHODS In this proof-of-concept study , 39 patients with early RA and clinical synovitis of the h and /wrist were r and omized to receive infusions with either zoledronic acid ( 5 mg ) or placebo , administered at baseline and week 13 . Patients in both groups received methotrexate ( MTX ) at a dosage of 7.5 - 20 mg/week . MRI and plain radiography were performed at baseline and week 26 . RESULTS At week 26 , the mean + /- SD change in MRI h and and wrist erosions was 61 % lower in the zoledronic acid group compared with the placebo group ( 0.9 + /- 1.63 versus 2.3 + /- 3.09 ; P = 0.176 ) . The mean + /- SD increase in the number of h and and wrist bones with erosions was 0.3 + /- 0.75 for zoledronic acid compared with 1.4 + /- 1.77 for placebo ( P = 0.029 ) . The proportion of patients in whom new MRI-visualized bone edema developed was smaller in the zoledronic acid group compared with the placebo group ( 33 % versus 58 % ; P = 0.121 ) . The zoledronic acid group had a mean change in the number of radiographic erosions of 0.1 compared with 0.5 for the placebo group ( P = 0.677 ) . The safety profile of zoledronic acid was similar to that of placebo . CONCLUSION The results of this study suggest a structural benefit associated with zoledronic acid therapy in patients with RA , as demonstrated by consistent results in structural end points in favor of zoledronic acid plus MTX compared with MTX alone OBJECTIVES To study the effect of oral clodronate on structural damage and bone metabolism in rheumatoid arthritis ( RA ) . METHODS In this 2-year proof-of-concept study , sixty patients with at least moderately active RA were r and omised to receive anti-rheumatic therapy alone or together with oral clodronate 1600 mg daily . Radiographs of h and s and feet and serum sample s for bone biomarkers were studied at baseline and at 24 months . RESULTS At 24 months , progression of radiographic joint damage was similar in the 2 groups . Clodronate suppressed carboxyterminal cross-linked peptide of type I collagen ( p=0.03 ) and aminoterminal propeptide of type I procollagen ( p=0.01 ) . Eight patients ( 27 % ) withdrew from clodronate therapy due to adverse drug reactions . CONCLUSIONS Oral clodronate did not retard the focal bone damage in RA despite its beneficial effect on overall bone metabolism , as judged by the decrease in the reference bone biomarkers Objectives To report results of subgroup analyses of bone mineral density ( BMD ) and bone turnover markers from a r and omised , double-blind , placebo-controlled , phase II study of denosumab , an investigational RANKL inhibitor , in patients with rheumatoid arthritis ( RA ) concurrently receiving treatment with bisphosphonates or glucocorticoids . Methods Patients received subcutaneous placebo ( n=75 ) , denosumab 60 mg ( n=71 ) or denosumab 180 mg ( n=72 ) at baseline and 6 months . Assessment s included dual x-ray absorptiometry scans of the lumbar spine and hip , and determination of levels of serum type I C-telopeptide ( sCTx- 
    Output:
    