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 and safety profiles of two different rituximab retreatment regimens in patients with RA . Methods . Four hundred and ninety-three RA patients with an inadequate response to MTX recruited into rituximab Phase II/III studies received further courses of open-label rituximab based on two approaches : ( i ) treatment to target ( TT ) : patients assessed 24 weeks after each course and retreated if not in remission [ DAS in 28 joints based on ESR ( DAS-28-ESR ) ≥ 2.6 ] ; ( ii ) treatment as needed ( PRN ) : patients retreated at the physician ’s discretion ≥24 weeks following the first course and ≥16 weeks following further courses , if both swollen and tender joint counts were ≥8 . All courses consisted of i.v . rituximab 2 × 1000 mg 2 weeks apart plus MTX . Observed data were analysed according to treatment strategy . Results . Multiple courses of rituximab maintained or improved responses irrespective of regimen . TT provided tighter control of disease activity with significantly greater improvements in DAS-28-ESR and lower HAQ-disability index scores vs PRN . TT result ed in significantly more patients achieving major clinical response . PRN result ed in recurrence of disease symptoms between courses , with TT significantly reducing the incidence of RA flares . Despite more frequent retreatment with TT compared with PRN , the rates of serious adverse events and serious infections were comparable between regimens . Conclusions . Retreatment with rituximab based on 24-week evaluations and to a target of DAS-28-ESR remission leads to improved efficacy and tighter control of disease activity compared with PRN without a compromised safety profile . TT may be the preferable rituximab treatment regimen for patients with RA Purpose To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis ( nr-axSpA ) . Methods Patients fulfilled Assessment of Spondyloarthritis international Society ( ASAS ) criteria for axial spondyloarthritis , had a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score of ≥ 4 , total back pain score of ≥ 4 ( 10 cm visual analogue scale ) and inadequate response , intolerance or contraindication to non-steroidal anti-inflammatory drugs ( NSAIDs ) ; patients fulfilling modified New York criteria for ankylosing spondylitis were excluded . Patients were r and omised to adalimumab ( N=91 ) or placebo ( N=94 ) . The primary endpoint was the percentage of patients achieving ASAS40 at week 12 . Efficacy assessment s included BASDAI and Ankylosing Spondylitis Disease Activity Score ( ASDAS ) . MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada ( SPARCC ) index . Results Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group ( 36 % vs 15 % , p<0.001 ) . Significant clinical improvements based on other ASAS responses , ASDAS and BASDAI were also detected at week 12 with adalimumab treatment , as were improvements in quality of life measures . Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment . Shorter disease duration , younger age , elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab . The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases . Conclusions In patients with nr-axSpA  , adalimumab treatment result ed in effective control of disease activity , decreased inflammation and improved quality of life  compared with placebo . Results from ABILITY-1 suggest that adalimumab has a positive benefit – risk profile in active nr-axSpA patients with inadequate response to NSAIDs Background To assess whether , in the real world of three early arthritis clinics , early referral could allow the best outcome , ie , remission , to be reached , and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa . Methods 1795 patients with early arthritis ( symptom duration ≤12 months ) were entered into a prospect i ve follow-up study . 711 patients ( 39.6 % ) were diagnosed with rheumatoid arthritis ( RA ) . Each RA patient was treated according to the local algorithm , in three tertiary referral centres ( representing a small province , a medium sized province and a metropolitan area , respectively ) . Remission , defined using the disease activity score in 28 joints ( DAS28 < 2.6 ) and American College of Rheumatology ( ACR ) criteria , was the major outcome evaluated at the 12-month follow-up . Results DAS28 remission was achieved in 34.3 % ( range 19.5–49 % ) of RA patients and ACR remission in 15.2 % ( range 8.5–20.6 % ) . At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome : being in very early rheumatoid arthritis ( VERA ; less than 12 weeks symptom duration at the time of first treatment ) and being on disease-modifying antirheumatic drugs ( DMARD ) within 3 months from disease onset . Among RA patients in remission , only 10 % of VERA subjects received an anti-TNF blocker compared with 32.2 % of non-VERA patients ( p=0.002 , OR 0.23 , 95 % CI 0.09 to 0.64 ) . Conclusions In a real-world setting , the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome , ie , remission of RA . Moreover , VERA represents a window of opportunity in terms of cost saving OBJECTIVE The objective of the EPISER study was to estimate the prevalence of rheumatoid arthritis ( RA ) , low back pain , h and and knee osteoarthritis ( OA ) , and fibromyalgia in the adult Spanish population , and to assess the impact of these diseases on function and quality of life , and use of health and social re sources . METHODS 2998 subjects aged 20 years or above were r and omly selected by stratified multistage cluster sampling from the censuses of 20 municipalities .  Trained rheumatologists carried out structured visits at which subjects were asked about rheumatic symptoms and sociodemographic characteristics , completed vali date d instruments for measuring function ( HAQ ) and  quality of life  ( SF-12 ) , and underwent a st and ardised physical examination . Cases were defined by previously vali date d criteria . RESULTS The estimated prevalences with 95 % confidence intervals were as follows : RA lifetime cumulative : 0.5 % ( 0.3 to 0.9 ) ; low back pain : 14.8 % ( 12.2 to 17.4 ) ; symptomatic knee OA : 10.2 % ( 8.5 to 11.9 ) ; h and OA : 6.2 % ( 5.9 to 6.5 ) ; fibromyalgia : 2.4 % ( 1.5 to 3.2 ) . Most conditions significantly impaired function and quality of life . CONCLUSIONS The EPISER study has internal and external validity for application of the results to the adult Spanish population . The diseases studied affect a significant proportion of the population , with various degrees of impact on disability and quality of life result ing in a significant number of physician visits , work disability , and medication use We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis ( AS ) . After 3 years of infliximab therapy , all AS patients ( n = 42 ) discontinued treatment ( time point (TP)1 ) and were visited regularly for 1 year in order to assess the time to relapse ( TP2 ) . Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and a physician 's global assessment ≥ 4 according to the recommendations of the Assessment s in Ankylosing Spondylitis ( ASAS ) working group . After 52 weeks , 41 of the 42 patients ( 97.6 % ) had to be reinfused because of relapse . The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician 's global assessment was 4.4 ± 1.8 ( both P < 0.001 ) . The mean time to relapse was 17.5 weeks ( ± 7.9 weeks , range 7 to 45 ) . Ten patients ( 24 % ) showed a relapse within 12 weeks and 38 patients ( 90.5 % ) , within 36 weeks . After 52 weeks , only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor . Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment . Retreatment with infliximab was safe and result ed in clinical improvement in all patients to a state similar to that before the treatment was stopped . Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice OBJECTIVE To evaluate the efficacy , pharmacokinetics , immunogenicity , and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody ( cA2 ) ( infliximab ; Remicade , Centocor , Malvern , PA ) given alone or in combination with low-dose methotrexate ( MTX ) in rheumatoid arthritis ( RA ) patients . METHODS In a 26-week , double-blind , placebo-controlled , multicenter trial , 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were r and omized to 1 of 7 groups of 14 - 15 patients each . The patients received either intravenous cA2 at 1 , 3 , or 10 mg/kg , with or without MTX 7.5 mg/week , or intravenous placebo plus MTX 7.5 mg/week at weeks 0 , 2 , 6 , 10 , and 14 and were followed up through week 26 . RESULTS Approximately 60 % of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20 % Paulus criteria for response to treatment , for a median duration of 10.4 to > 18.1 weeks ( P < 0.001 versus placebo ) . Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 ( median duration 2.6 weeks ; P=0.126 versus placebo ) . However , coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic , prolonging the duration of the 20 % response in > 60 % of patients to a median of 16.5 weeks ( P < 0.001 versus placebo ; P=0.006 versus no MTX ) and the 50 % response to 12.2 weeks ( P < 0.001 versus placebo ; P=0.002 versus no MTX ) . Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease , with a Paulus response lasting a median of 0 weeks . A 70 - 90 % reduction in the swollen joint count , tender joint count , and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX . In general , treatment was well tolerated and stable blood levels of cA2 were achieved in all groups , except for the group receiving 1 mg/kg of cA 
    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 and safety profiles of two different rituximab retreatment regimens in patients with RA . Methods . Four hundred and ninety-three RA patients with an inadequate response to MTX recruited into rituximab Phase II/III studies received further courses of open-label rituximab based on two approaches : ( i ) treatment to target ( TT ) : patients assessed 24 weeks after each course and retreated if not in remission [ DAS in 28 joints based on ESR ( DAS-28-ESR ) ≥ 2.6 ] ; ( ii ) treatment as needed ( PRN ) : patients retreated at the physician ’s discretion ≥24 weeks following the first course and ≥16 weeks following further courses , if both swollen and tender joint counts were ≥8 . All courses consisted of i.v . rituximab 2 × 1000 mg 2 weeks apart plus MTX . Observed data were analysed according to treatment strategy . Results . Multiple courses of rituximab maintained or improved responses irrespective of regimen . TT provided tighter control of disease activity with significantly greater improvements in DAS-28-ESR and lower HAQ-disability index scores vs PRN . TT result ed in significantly more patients achieving major clinical response . PRN result ed in recurrence of disease symptoms between courses , with TT significantly reducing the incidence of RA flares . Despite more frequent retreatment with TT compared with PRN , the rates of serious adverse events and serious infections were comparable between regimens . Conclusions . Retreatment with rituximab based on 24-week evaluations and to a target of DAS-28-ESR remission leads to improved efficacy and tighter control of disease activity compared with PRN without a compromised safety profile . TT may be the preferable rituximab treatment regimen for patients with RA Purpose To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis ( nr-axSpA ) . Methods Patients fulfilled Assessment of Spondyloarthritis international Society ( ASAS ) criteria for axial spondyloarthritis , had a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score of ≥ 4 , total back pain score of ≥ 4 ( 10 cm visual analogue scale ) and inadequate response , intolerance or contraindication to non-steroidal anti-inflammatory drugs ( NSAIDs ) ; patients fulfilling modified New York criteria for ankylosing spondylitis were excluded . Patients were r and omised to adalimumab ( N=91 ) or placebo ( N=94 ) . The primary endpoint was the percentage of patients achieving ASAS40 at week 12 . Efficacy assessment s included BASDAI and Ankylosing Spondylitis Disease Activity Score ( ASDAS ) . MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada ( SPARCC ) index . Results Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group ( 36 % vs 15 % , p<0.001 ) . Significant clinical improvements based on other ASAS responses , ASDAS and BASDAI were also detected at week 12 with adalimumab treatment , as were improvements in quality of life measures . Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment . Shorter disease duration , younger age , elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab . The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases . Conclusions In patients with nr-axSpA  , adalimumab treatment result ed in effective control of disease activity , decreased inflammation and improved quality of life  compared with placebo . Results from ABILITY-1 suggest that adalimumab has a positive benefit – risk profile in active nr-axSpA patients with inadequate response to NSAIDs Background To assess whether , in the real world of three early arthritis clinics , early referral could allow the best outcome , ie , remission , to be reached , and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa . Methods 1795 patients with early arthritis ( symptom duration ≤12 months ) were entered into a prospect i ve follow-up study . 711 patients ( 39.6 % ) were diagnosed with rheumatoid arthritis ( RA ) . Each RA patient was treated according to the local algorithm , in three tertiary referral centres ( representing a small province , a medium sized province and a metropolitan area , respectively ) . Remission , defined using the disease activity score in 28 joints ( DAS28 < 2.6 ) and American College of Rheumatology ( ACR ) criteria , was the major outcome evaluated at the 12-month follow-up . Results DAS28 remission was achieved in 34.3 % ( range 19.5–49 % ) of RA patients and ACR remission in 15.2 % ( range 8.5–20.6 % ) . At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome : being in very early rheumatoid arthritis ( VERA ; less than 12 weeks symptom duration at the time of first treatment ) and being on disease-modifying antirheumatic drugs ( DMARD ) within 3 months from disease onset . Among RA patients in remission , only 10 % of VERA subjects received an anti-TNF blocker compared with 32.2 % of non-VERA patients ( p=0.002 , OR 0.23 , 95 % CI 0.09 to 0.64 ) . Conclusions In a real-world setting , the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome , ie , remission of RA . Moreover , VERA represents a window of opportunity in terms of cost saving OBJECTIVE The objective of the EPISER study was to estimate the prevalence of rheumatoid arthritis ( RA ) , low back pain , h and and knee osteoarthritis ( OA ) , and fibromyalgia in the adult Spanish population , and to assess the impact of these diseases on function and quality of life , and use of health and social re sources . METHODS 2998 subjects aged 20 years or above were r and omly selected by stratified multistage cluster sampling from the censuses of 20 municipalities .  Trained rheumatologists carried out structured visits at which subjects were asked about rheumatic symptoms and sociodemographic characteristics , completed vali date d instruments for measuring function ( HAQ ) and  quality of life  ( SF-12 ) , and underwent a st and ardised physical examination . Cases were defined by previously vali date d criteria . RESULTS The estimated prevalences with 95 % confidence intervals were as follows : RA lifetime cumulative : 0.5 % ( 0.3 to 0.9 ) ; low back pain : 14.8 % ( 12.2 to 17.4 ) ; symptomatic knee OA : 10.2 % ( 8.5 to 11.9 ) ; h and OA : 6.2 % ( 5.9 to 6.5 ) ; fibromyalgia : 2.4 % ( 1.5 to 3.2 ) . Most conditions significantly impaired function and quality of life . CONCLUSIONS The EPISER study has internal and external validity for application of the results to the adult Spanish population . The diseases studied affect a significant proportion of the population , with various degrees of impact on disability and quality of life result ing in a significant number of physician visits , work disability , and medication use We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis ( AS ) . After 3 years of infliximab therapy , all AS patients ( n = 42 ) discontinued treatment ( time point (TP)1 ) and were visited regularly for 1 year in order to assess the time to relapse ( TP2 ) . Relapse was defined as an increase to a value ≥ 4 on the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and a physician 's global assessment ≥ 4 according to the recommendations of the Assessment s in Ankylosing Spondylitis ( ASAS ) working group . After 52 weeks , 41 of the 42 patients ( 97.6 % ) had to be reinfused because of relapse . The mean change in the BASDAI between TP1 and TP2 was 3.6 ± 1.7 and that in the physician 's global assessment was 4.4 ± 1.8 ( both P < 0.001 ) . The mean time to relapse was 17.5 weeks ( ± 7.9 weeks , range 7 to 45 ) . Ten patients ( 24 % ) showed a relapse within 12 weeks and 38 patients ( 90.5 % ) , within 36 weeks . After 52 weeks , only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor . Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment . Retreatment with infliximab was safe and result ed in clinical improvement in all patients to a state similar to that before the treatment was stopped . Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one Background : To investigate whether intensive treatment with methotrexate ( MTX ) according to a strict protocol and a computerised decision program is more beneficial compared to conventional treatment with MTX in early rheumatoid arthritis . Methods : In a two-year multicentre open label strategy trial , 299 patients with early rheumatoid arthritis were r and omly assigned to the intensive strategy group or the conventional strategy group . Patients in both groups received MTX , the aim of treatment being remission . Patients in the intensive treatment group came to the outpatient clinic once every month ; adjustment of the MTX dosage was tailored to the individual patient on the basis of predefined response criteria , using a computerised decision program . Patients of the conventional strategy group came to the outpatient clinic once every three months ; they were treated according to common practice . Cyclosporine was added if patients had an inadequate response to maximal tolerated MTX doses . Results : Seventy six ( 50 % ) patients in the intensive strategy group achieved at least one period of remission during the two year trial , versus 55 patients ( 37 % ) in the conventional strategy group ( p = 0.03 ) . Areas under the curve for nearly all clinical variables were significantly lower — that is , there was a better clinical effect for the intensive treatment group compared with the conventional treatment group . Conclusion : The results of this study show that it is possible to substantially enhance the clinical efficacy early in the course of the disease by intensifying treatment with MTX , aim ing for remission , tailored to the individual patient . Furthermore , participating rheumatologists indicated that the computerised decision program could be a helpful tool in their daily clinical practice OBJECTIVE To evaluate the efficacy , pharmacokinetics , immunogenicity , and safety of multiple infusions of a chimeric monoclonal anti-tumor necrosis factor alpha antibody ( cA2 ) ( infliximab ; Remicade , Centocor , Malvern , PA ) given alone or in combination with low-dose methotrexate ( MTX ) in rheumatoid arthritis ( RA ) patients . METHODS In a 26-week , double-blind , placebo-controlled , multicenter trial , 101 patients with active RA exhibiting an incomplete response or flare of disease activity while receiving low-dose MTX were r and omized to 1 of 7 groups of 14 - 15 patients each . The patients received either intravenous cA2 at 1 , 3 , or 10 mg/kg , with or without MTX 7.5 mg/week , or intravenous placebo plus MTX 7.5 mg/week at weeks 0 , 2 , 6 , 10 , and 14 and were followed up through week 26 . RESULTS Approximately 60 % of patients receiving cA2 at 3 or 10 mg/kg with or without MTX achieved the 20 % Paulus criteria for response to treatment , for a median duration of 10.4 to > 18.1 weeks ( P < 0.001 versus placebo ) . Patients receiving cA2 at 1 mg/kg without MTX became unresponsive to repeated infusions of cA2 ( median duration 2.6 weeks ; P=0.126 versus placebo ) . However , coadministration of cA2 at 1 mg/kg with MTX appeared to be synergistic , prolonging the duration of the 20 % response in > 60 % of patients to a median of 16.5 weeks ( P < 0.001 versus placebo ; P=0.006 versus no MTX ) and the 50 % response to 12.2 weeks ( P < 0.001 versus placebo ; P=0.002 versus no MTX ) . Patients receiving placebo infusions plus suboptimal low-dose MTX continued to have active disease , with a Paulus response lasting a median of 0 weeks . A 70 - 90 % reduction in the swollen joint count , tender joint count , and C-reactive protein level was maintained for the entire 26 weeks in patients receiving 10 mg/kg of cA2 with MTX . In general , treatment was well tolerated and stable blood levels of cA2 were achieved in all groups , except for the group receiving 1 mg/kg of cA 
    Output:
    