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 : Patients with rheumatoid arthritis ( RA ) with an inadequate response to TNF antagonists ( aTNFs ) may switch to an alternative aTNF or start treatment from a different class of drugs , such as rituximab ( RTX ) . It remains unclear in which clinical setting s these therapeutic strategies offer most benefit . Objective : To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients . Methods : A prospect i ve cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF , nested within the Swiss RA registry ( SCQM-RA ) was carried out . The primary outcome , longitudinal improvement in 28-joint count Disease Activity Score ( DAS28 ) , was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders . Results : Of the 318 patients with RA included ; 155 received RTX and 163 received an alternative aTNF . The relative benefit of RTX varied with the type of prior aTNF failure : when the motive for switching was ineffectiveness to previous aTNFs , the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF ( p = 0.03 ; at 6 months , −1.34 ( 95 % CI −1.54 to −1.15 ) vs −0.93 ( 95 % CI −1.28 to −0.59 ) , respectively ) . When the motive for switching was other causes , the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs ( p = 0.40 ) . These results were not significantly modified by the number of previous aTNF failures , the type of aTNF switches , or the presence of co-treatment with a disease-modifying antirheumatic drug . Conclusion : This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF Objective To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients . Methods Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab ( n = 57 ) or tocilizumab ( n = 70 ) treatment were included in our prospect i ve cohort study . Our cohort started in February 2010 , and the patients observed for at least 1 year as of April 2013 were analysed . We assessed baseline variables including patients ' characteristics ( age , sex , disease duration , prednisolone dose , methotrexate dose , other disease-modifying antirheumatic drug use , Clinical Disease Activity Index [ CDAI ] ) and serum biomarker levels ( C-reactive protein , immunoglobulin M-rheumatoid factor , anti-cyclic citrullinated protein/peptide antibodies , interferon-γ , interleukin (IL)-1β , IL-2 , IL-6 , IL-8 , IL-10 , IL-17 , tumor necrosis factor-α , soluble intercellular adhesion molecule-1 , bone alkaline phosphatase , osteonectin , osteopontin ) to extract factors associated with clinical remission ( CDAI≤2.8 ) at 1 year using univariate analyses , and the extracted factors were entered into a multivariate logistic regression model . Similar analyses were also performed for Simplified Disease Activity Index ( SDAI ) remission ( ≤3.3 ) and Disease Activity Score with 28 joint counts , erythrocyte sedimentation rate ( DAS28-ESR ) remission ( < 2.6 ) . Results There were no significant differences in the baseline characteristics except for methotrexate use between the groups . In the multivariate analyses , the low baseline osteopontin levels ( OR 0.9145 , 95 % CI 0.8399–0.9857 ) were identified as predictors of CDAI remission in the tocilizumab group , whereas no predictors of CDAI remission were found in the infliximab group . Similar results were obtained when using SDAI and DAS28-ESR remission criteria . Conclusion Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis . Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts Background / objective Progression of joint damage is linked to disease activity . This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate ( MTX ) . It is hitherto unknown if this may also be true for therapies targeting B-cells . We thus evaluated if rituximab ( RTX ) therapy inhibits joint damage irrespective of its effects on disease activity . Methods We used a r and om 90 % sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis ( RA ) receiving MTX ( n=188 ) or MTX+RTX 1000 mg ( n=204 ) . Patients were divided into low , moderate and high disease activity at one year of treatment by simplified disease activity index ( low disease activity ( LDA ) , moderate disease activity ( MDA ) , high disease activity ( HDA ) ) , or by swollen joint count ( SJC ) or C reactive protein ( CRP ) tertiles . Progression of damage by the Genant modified total Sharp score ( TGSS ) was compared between therapies ( Kruskal-Wallis , Wilcoxon tests ) for each of these subgroups . Results In patients treated with MTX , 1-year progression of TGSS In LDA , MDA and HDA was 0.40±0.88 , 1.04±1.73 , and 1.31±3.02 , respectively . In contrast , on RTX+MTX  , TGSS progression was 0.38±1.07 , 0.39±1.28 , and −0.05±0.44 , respectively ( for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group : p=0.003 and p=0.05 , respectively ) . Additional analyses ( tertiles of SJC , CRP , and matching for disease activity ) confirmed the primary analysis . Conclusions In early RA , progression of joint damage increases with increasing disease activity on MTX . RTX plus MTX retards damage independently of its effects on disease activity , since even in HDA destruction is halted , contrasting MTX monotherapy . This indicates that beyond cytokine blockade ( TNF- and IL-6 inhibitors ) , also cell-directed therapy ( anti-CD20 antibody ) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage OBJECTIVES To describe the changes in functional ability ( FA ) taking place over 5 yr in patients with rheumatoid arthritis ( RA ) starting disease-modifying anti-rheumatic drug ( DMARD ) therapy  , to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment . METHODS Three hundred and sixty-six patients with active RA were studied as part of a 5-yr r and omized controlled study of DMARD therapy . FA was assessed by  Health Assessment Question naire  ( HAQ )  score every 6 months . Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr . The independent variables used were age , sex , visual analogue scale ( VAS ) pain , Ritchie articular index , C-reactive protein ( CRP ) , Larsen score and log-transformed morning stiffness ( EMS ) . RESULTS Mean HAQ score was 1.64 at baseline , improved by 21 % at 1 yr and gradually returned towards baseline levels by 5 yr . At baseline only 34 % of variance in HAQ score could be explained ; the most significant explanatory variables were the Ritchie articular index and CRP . At 5 yr the variance explained was 60 % . The Ritchie articular index remained the strongest factor followed by VAS pain , log(10 ) EMS and Larsen score . CONCLUSIONS Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr . The most consistent factor affecting function was joint tenderness . Global pain and duration of EMS were of lesser importance . Disease activity measures such as the CRP exerted an influence in the earlier , more active stages of disease : radiographic damage assumed greater importance as the arthritis progressed OBJECTIVE To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in h and s and feet in rheumatoid arthritis . METHODS 183 patients with early rheumatoid arthritis included in a prospect i ve study were examined . Radiographic changes in h and s and feet at 5 and 10 years after inclusion were evaluated ( Larsen ) . The markers analysed were : erythrocyte sedimentation rate ( ESR ) ; HLA-DRB alleles typed by restriction fragment length polymorphism ; and C reactive protein , cartilage oligomeric matrix protein ( COMP ) , rheumatoid factor ( RF ) ( IgG , IgA , and IgM subtypes ) , antibodies against cyclic citrullinated peptide ( anti-CCP ) , and antibodies against interleukin 1alpha ( anti-IL1alpha ) , analysed by immunoassays . Multiple linear regression with backward elimination was used to determine the prognostic value of the variables . RESULTS 117/176 patients were positive for IgG RF , 138/176 for IgA RF , 139/176 for IgM RF , 140/176 for anti-CCP , and 40/182 for anti-IL1alpha . After five years , ESR , the presence of IgA RF , serum COMP , and the presence of anti-CCP were significantly associated with more severe joint damage , and the presence of anti-IL1alpha with less severe joint damage . Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years . A stronger prediction was obtained by combining the prognostic factors . CONCLUSIONS Early determination of anti-CCP , IgA RF , anti-IL-1alpha , ESR , C reactive protein , and COMP predicted the development of joint damage in h and s and feet in this cohort . A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis OBJECTIVES To predict the long-term outcome of rheumatoid arthritis ( RA ) with respect to radiographic damage , disability , and disease course using baseline variables , and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions . METHODS The 12-year outcome of 112 female RA patients from a prospect i ve inception cohort was assessed by measuring the tertiles of radiographic damage ( measured by the modified Sharp/van der Heijde method , SHS ) , disability ( measured by the Health Assessment Question naire , HAQ ) , and severe disease course as defined by patients with either the 33 % highest cumulative disease activity ( area under the curve of all observed disease activity scores ) or the highest tertile of radiographic damage . Patients in the lowest ( mild ) and highest tertile ( severe ) of each outcome measure were identified . All baseline parameters known to be associated with each outcome ( demographic and socioeconomic parameters ; disease duration ; disease activity measures ; laboratory measures including rheumatoid factor , HLA typing , percentage agalactosyl IgG , functional and radiographic measures ) were entered into cross-vali date d stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes . Using the results of the logistic regression models , simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group . RESULTS After 12 years , the lowest and highest tertiles were , respectively , 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ . Fifty-five patients had a severe disease course . Mild and severe radiographic damage could be predicted with an accuracy of 90 % and 85 % , respectively . Mild and severe HAQ could be predicted with an accuracy of 90 % and 84 % , respectively , and severe disease course with an accuracy of 81 % . The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters : swollen joint count ( SJC ) , Ritchie score , rheumatoid factor ( RF ) , the presence of erosions , and the HAQ score . Additional knowledge of the HLA typing hardly improved the accuracy of the prediction . To predict outcome at the individual level , simple decision trees were constructed using the RF , HAQ , SJC , and presence of erosions at baseline . CONCLUSION The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters Seventy two patients with classical or definite rheumatoid arthritis ( RA ) were r and omly allocated to receive gold or D-penicillamine therapy ( DPA ) in a prospect i ve study design ed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy . Forty five patients completed 12 months ' treatment . There were no significant demographic or clinical differences between them and the 27 drop outs . Twenty of the 45 patients showed no radiological progression between six and 12 months . These patients had less severe initial radiological damage , lower levels of serum aspart 
    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 : Patients with rheumatoid arthritis ( RA ) with an inadequate response to TNF antagonists ( aTNFs ) may switch to an alternative aTNF or start treatment from a different class of drugs , such as rituximab ( RTX ) . It remains unclear in which clinical setting s these therapeutic strategies offer most benefit . Objective : To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients . Methods : A prospect i ve cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF , nested within the Swiss RA registry ( SCQM-RA ) was carried out . The primary outcome , longitudinal improvement in 28-joint count Disease Activity Score ( DAS28 ) , was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders . Results : Of the 318 patients with RA included ; 155 received RTX and 163 received an alternative aTNF . The relative benefit of RTX varied with the type of prior aTNF failure : when the motive for switching was ineffectiveness to previous aTNFs , the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF ( p = 0.03 ; at 6 months , −1.34 ( 95 % CI −1.54 to −1.15 ) vs −0.93 ( 95 % CI −1.28 to −0.59 ) , respectively ) . When the motive for switching was other causes , the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs ( p = 0.40 ) . These results were not significantly modified by the number of previous aTNF failures , the type of aTNF switches , or the presence of co-treatment with a disease-modifying antirheumatic drug . Conclusion : This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF Objective To explore the baseline predictors of clinical effectiveness after tocilizumab or infliximab treatment in biologic-naïve rheumatoid arthritis patients . Methods Consecutive biologic-naïve patients with rheumatoid arthritis initiating infliximab ( n = 57 ) or tocilizumab ( n = 70 ) treatment were included in our prospect i ve cohort study . Our cohort started in February 2010 , and the patients observed for at least 1 year as of April 2013 were analysed . We assessed baseline variables including patients ' characteristics ( age , sex , disease duration , prednisolone dose , methotrexate dose , other disease-modifying antirheumatic drug use , Clinical Disease Activity Index [ CDAI ] ) and serum biomarker levels ( C-reactive protein , immunoglobulin M-rheumatoid factor , anti-cyclic citrullinated protein/peptide antibodies , interferon-γ , interleukin (IL)-1β , IL-2 , IL-6 , IL-8 , IL-10 , IL-17 , tumor necrosis factor-α , soluble intercellular adhesion molecule-1 , bone alkaline phosphatase , osteonectin , osteopontin ) to extract factors associated with clinical remission ( CDAI≤2.8 ) at 1 year using univariate analyses , and the extracted factors were entered into a multivariate logistic regression model . Similar analyses were also performed for Simplified Disease Activity Index ( SDAI ) remission ( ≤3.3 ) and Disease Activity Score with 28 joint counts , erythrocyte sedimentation rate ( DAS28-ESR ) remission ( < 2.6 ) . Results There were no significant differences in the baseline characteristics except for methotrexate use between the groups . In the multivariate analyses , the low baseline osteopontin levels ( OR 0.9145 , 95 % CI 0.8399–0.9857 ) were identified as predictors of CDAI remission in the tocilizumab group , whereas no predictors of CDAI remission were found in the infliximab group . Similar results were obtained when using SDAI and DAS28-ESR remission criteria . Conclusion Baseline low serum osteopontin levels predict clinical remission 1 year after tocilizumab treatment and not infliximab treatment in biologic-naïve patients with rheumatoid arthritis . Our prediction model provided insights into how to optimize the choice of biologics and warrants external validation in other cohorts Background / objective Progression of joint damage is linked to disease activity . This link is dissociated upon treatment with tumour necrosis factor (TNF)- or IL-6-inhibitors plus methotrexate ( MTX ) . It is hitherto unknown if this may also be true for therapies targeting B-cells . We thus evaluated if rituximab ( RTX ) therapy inhibits joint damage irrespective of its effects on disease activity . Methods We used a r and om 90 % sample of data from two arms of the IMAGE trial comprising patients with active early rheumatoid arthritis ( RA ) receiving MTX ( n=188 ) or MTX+RTX 1000 mg ( n=204 ) . Patients were divided into low , moderate and high disease activity at one year of treatment by simplified disease activity index ( low disease activity ( LDA ) , moderate disease activity ( MDA ) , high disease activity ( HDA ) ) , or by swollen joint count ( SJC ) or C reactive protein ( CRP ) tertiles . Progression of damage by the Genant modified total Sharp score ( TGSS ) was compared between therapies ( Kruskal-Wallis , Wilcoxon tests ) for each of these subgroups . Results In patients treated with MTX , 1-year progression of TGSS In LDA , MDA and HDA was 0.40±0.88 , 1.04±1.73 , and 1.31±3.02 , respectively . In contrast , on RTX+MTX  , TGSS progression was 0.38±1.07 , 0.39±1.28 , and −0.05±0.44 , respectively ( for MDA and HDA the progression of TGSS was significantly lower in the combined group than in the MTX group : p=0.003 and p=0.05 , respectively ) . Additional analyses ( tertiles of SJC , CRP , and matching for disease activity ) confirmed the primary analysis . Conclusions In early RA , progression of joint damage increases with increasing disease activity on MTX . RTX plus MTX retards damage independently of its effects on disease activity , since even in HDA destruction is halted , contrasting MTX monotherapy . This indicates that beyond cytokine blockade ( TNF- and IL-6 inhibitors ) , also cell-directed therapy ( anti-CD20 antibody ) conveys profound anti-destructive effects and dissociates the link between disease activity and joint damage OBJECTIVES To describe the changes in functional ability ( FA ) taking place over 5 yr in patients with rheumatoid arthritis ( RA ) starting disease-modifying anti-rheumatic drug ( DMARD ) therapy  , to investigate the factors having most influence upon FA and to compare these factors at baseline and after 5 yr of treatment . METHODS Three hundred and sixty-six patients with active RA were studied as part of a 5-yr r and omized controlled study of DMARD therapy . FA was assessed by  Health Assessment Question naire  ( HAQ )  score every 6 months . Multiple linear regression was used to identify factors affecting FA at baseline and at 5 yr . The independent variables used were age , sex , visual analogue scale ( VAS ) pain , Ritchie articular index , C-reactive protein ( CRP ) , Larsen score and log-transformed morning stiffness ( EMS ) . RESULTS Mean HAQ score was 1.64 at baseline , improved by 21 % at 1 yr and gradually returned towards baseline levels by 5 yr . At baseline only 34 % of variance in HAQ score could be explained ; the most significant explanatory variables were the Ritchie articular index and CRP . At 5 yr the variance explained was 60 % . The Ritchie articular index remained the strongest factor followed by VAS pain , log(10 ) EMS and Larsen score . CONCLUSIONS Improvement in function did occur after commencement of the first DMARD therapy but was not maintained to 5 yr . The most consistent factor affecting function was joint tenderness . Global pain and duration of EMS were of lesser importance . Disease activity measures such as the CRP exerted an influence in the earlier , more active stages of disease : radiographic damage assumed greater importance as the arthritis progressed OBJECTIVE To investigate whether determination of a set of laboratory markers at baseline provides prognostic information on joint damage in h and s and feet in rheumatoid arthritis . METHODS 183 patients with early rheumatoid arthritis included in a prospect i ve study were examined . Radiographic changes in h and s and feet at 5 and 10 years after inclusion were evaluated ( Larsen ) . The markers analysed were : erythrocyte sedimentation rate ( ESR ) ; HLA-DRB alleles typed by restriction fragment length polymorphism ; and C reactive protein , cartilage oligomeric matrix protein ( COMP ) , rheumatoid factor ( RF ) ( IgG , IgA , and IgM subtypes ) , antibodies against cyclic citrullinated peptide ( anti-CCP ) , and antibodies against interleukin 1alpha ( anti-IL1alpha ) , analysed by immunoassays . Multiple linear regression with backward elimination was used to determine the prognostic value of the variables . RESULTS 117/176 patients were positive for IgG RF , 138/176 for IgA RF , 139/176 for IgM RF , 140/176 for anti-CCP , and 40/182 for anti-IL1alpha . After five years , ESR , the presence of IgA RF , serum COMP , and the presence of anti-CCP were significantly associated with more severe joint damage , and the presence of anti-IL1alpha with less severe joint damage . Baseline C reactive protein and anti-CCP predicted radiographic outcome after 10 years . A stronger prediction was obtained by combining the prognostic factors . CONCLUSIONS Early determination of anti-CCP , IgA RF , anti-IL-1alpha , ESR , C reactive protein , and COMP predicted the development of joint damage in h and s and feet in this cohort . A combination of these measures reflecting different aspects of the disease process should be useful for evaluating prognosis in individual patients with early rheumatoid arthritis OBJECTIVES To predict the long-term outcome of rheumatoid arthritis ( RA ) with respect to radiographic damage , disability , and disease course using baseline variables , and to construct decision trees identifying patients on an individual level at the extremes of the outcome spectrum of these 3 dimensions . METHODS The 12-year outcome of 112 female RA patients from a prospect i ve inception cohort was assessed by measuring the tertiles of radiographic damage ( measured by the modified Sharp/van der Heijde method , SHS ) , disability ( measured by the Health Assessment Question naire , HAQ ) , and severe disease course as defined by patients with either the 33 % highest cumulative disease activity ( area under the curve of all observed disease activity scores ) or the highest tertile of radiographic damage . Patients in the lowest ( mild ) and highest tertile ( severe ) of each outcome measure were identified . All baseline parameters known to be associated with each outcome ( demographic and socioeconomic parameters ; disease duration ; disease activity measures ; laboratory measures including rheumatoid factor , HLA typing , percentage agalactosyl IgG , functional and radiographic measures ) were entered into cross-vali date d stepwise logistic regression models to find the best predictive combination of baseline parameters for each of the outcomes . Using the results of the logistic regression models , simple decision trees were constructed to categorize patients at an individual level in a particular prognostic group . RESULTS After 12 years , the lowest and highest tertiles were , respectively , 42.3 and 189 for the SHS and 0.37 and 1.25 for the HAQ . Fifty-five patients had a severe disease course . Mild and severe radiographic damage could be predicted with an accuracy of 90 % and 85 % , respectively . Mild and severe HAQ could be predicted with an accuracy of 90 % and 84 % , respectively , and severe disease course with an accuracy of 81 % . The baseline variables found to be predictive of all 3 outcome measures were very similar and consisted of combinations of the following baseline parameters : swollen joint count ( SJC ) , Ritchie score , rheumatoid factor ( RF ) , the presence of erosions , and the HAQ score . Additional knowledge of the HLA typing hardly improved the accuracy of the prediction . To predict outcome at the individual level , simple decision trees were constructed using the RF , HAQ , SJC , and presence of erosions at baseline . CONCLUSION The present study shows that prediction of outcome in long-term RA is possible and can be done using widely available baseline parameters Seventy two patients with classical or definite rheumatoid arthritis ( RA ) were r and omly allocated to receive gold or D-penicillamine therapy ( DPA ) in a prospect i ve study design ed to evaluate whether it is possible to predict which patients will show radiological progression despite therapy . Forty five patients completed 12 months ' treatment . There were no significant demographic or clinical differences between them and the 27 drop outs . Twenty of the 45 patients showed no radiological progression between six and 12 months . These patients had less severe initial radiological damage , lower levels of serum aspart 
    Output:
    