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 examine the characteristics and frequency of disease flares in a cohort of people with AS . Methods . A prospect i ve data set from a r and omized controlled trial ( RCT ) of a probiotic treatment/placebo was utilized to examine disease flares in 134 people with AS . Disease flares were defined as either minor/localized flares ( pain/swelling localized to one area with fatigue and stiffness ) or major/generalized flares ( generalized pain , hot burning joints , muscle spasm , fever , sweating , extreme fatigue and stiffness ) . Results . One hundred and thirty-four people were followed up for 1216 person follow-up weeks and there were 71.4 flares per 100 person-weeks . Of these , 12 were major/generalized flares and 59.4 were minor/localized flares . People who experienced at least one major/generalized flare during the study period had worse disease during flare-free periods in terms of disease activity , impaired function , self-reported night pain and iritis compared with those who did not experience any major/generalized flares during the study . Major/generalized flares lasted for an average of 2.4 weeks ( s.d . 2.7 ) , and were preceded by and followed by a minor/localized flare in 92 % ( 55/60 ) of cases . Conclusion . Seventy per cent of people with AS felt they had a flare in any given week . Those who experienced major/generalized flares appear to have more severe and active disease even during periods when not in flare , compared with those who do not experience major/generalized flares . These results have implication s for the timing of assessment s prior to starting anti-TNF therapy and suggest that the presence of major flares may be helpful in identifying patients with severe disease Objective . Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK . This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and Bath Ankylosing Spondylitis Functional Index ( BASFI ) after 6 months of therapy in 261 patients enrolled in a national prospect i ve observational register . Methods . The British Society for Rheumatology Biologics Register ( BSRBR ) recruited patients starting anti-TNF therapy for AS between 2002 and 2006 . Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months . Covariates included age , gender , disease duration , baseline BASDAI and BASFI , presence of raised inflammatory markers ( defined as twice the upper limit of normal ) and DMARD therapy . Results . The cohort was young ( median age 43 years ) and 82 % were males .  Median baseline BASDAI was 7.6 and BASFI 7.9 . At 6 months , the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U , respectively ; 52 % reached a BASDAI50 . Patients with raised inflammatory markers at the start of therapy had a 0.9-U ( 95 % CI 0.2 , 1.5 ) better improvement in BASDAI compared with those without . Lesser responses were seen in those with higher baseline BASFI scores . Women had a 1.1-U ( 95 % CI 0.3 , 2.0 ) greater improvement in BASFI at 6 months , as did those who were receiving concurrent DMARD therapy [ 0.9 U ( 95 % CI 0.2 , 1.7 ) ] . Conclusions . The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity . Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI , identifying a group of patients who may be more responsive to anti-TNF therapies , although the results were not confined to this group Objectives To assess whether combination therapy with infliximab ( IFX ) plus nonsteroidal anti-inflammatory drugs ( NSAIDs ) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society ( ASAS ) partial remission in patients with early , active axial spondyloarthritis ( SpA ) who were naïve to NSAIDs or received a submaximal dose of NSAIDs . Methods Patients were r and omised ( 2 : 1 ratio ) to receive naproxen ( NPX ) 1000 mg daily plus either IFX 5 mg/kg or placebo ( PBO ) at weeks 0 , 2 , 6 , 12 , 18 and 24 . The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28 . Several other measures of disease activity , clinical symptoms and patient-rated outcomes were evaluated . Treatment group differences were analysed with Fisher exact tests or analysis of covariance . Results A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group ( 61.9 % ; 65/105 ) than in the PBO+NPX group ( 35.3 % ; 18/51 ) at week 28 ( p=0.002 ) and at all other visits ( p<0.05 , all comparisons ) . Results of most other disease activity and patient-reported endpoints ( including Ankylosing Spondylitis Disease Activity Score , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , multiple quality of life measures and pain measures ) showed greater improvement in the IFX+NPX group than the PBO+NPX group , with several measures demonstrating early and consistent improvement over 28 weeks of treatment . Conclusions Patients with early , active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone . NPX alone led to clinical remission in a third of patients Objective : A double blind , r and omised , placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis ( AS ) . Methods : Adult patients with AS at 14 European sites were r and omly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks . The primary efficacy end point was an improvement of at least 20 % in patient reported symptoms , based on the multicomponent Assessment s in Ankylosing Spondylitis ( ASAS ) response criteria ( ASAS 20 ) . Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , acute phase reactants , and spinal mobility tests . Safety was evaluated during scheduled visits . Results : Of 84 patients enrolled , 45 received etanercept and 39 received placebo . Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2 , and sustained differences were evident up to week 12 . Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2 , 4 , and 8 ; reported lower composite and fatigue BASDAI scores ; had lower acute phase reactant levels ; and had improved spinal flexion .  Etanercept was well tolerated . Most adverse events were mild to moderate ; the only between-group difference was injection site reactions , which occurred significantly more often in etanercept patients . Conclusions : Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS Objectives To compare the pharmacokinetics ( PK ) , safety and efficacy of innovator infliximab ( INX ) and CT-P13 , a biosimilar to INX , in patients with active ankylosing spondylitis ( AS ) . Methods Phase 1 r and omised , double-blind , multicentre , multinational , parallel-group study . Patients were r and omised to receive 5 mg/kg of CT-P13 ( n=125 ) or INX ( n=125 ) . Primary endpoints were area under the concentration-time curve ( AUC ) at steady state and observed maximum steady state serum concentration ( Cmax , ss ) between weeks 22 and 30 . Additional PK , efficacy endpoints , including 20 % and 40 % improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria ( ASAS20 and ASAS40 ) , and safety outcomes were also assessed . Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX . Geometric mean Cmax , ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX . The ratio of geometric means was 104.5 % ( 90 % CI 94 % to 116 % ) for AUC and 101.5 % ( 90 % CI 95 % to 109 % ) for Cmax , ss . ASAS20 and ASAS40 responses at week 30 were 70.5 % and 51.8 % for CT-P13 and 72.4 % and 47.4 % for INX , respectively . In the CT-P13 and INX groups more than one adverse event occurred in 64.8 % and 63.9 % of patients , infusion reactions occurred in 3.9 % and 4.9 % , active tuberculosis occurred in 1.6 % and 0.8 % , and 27.4 % and 22.5 % of patients tested positive for anti-drug antibodies , respectively . Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS . CT-P13 was well tolerated , with an efficacy and safety profile comparable to that of INX up to week 30 OBJECTIVE Our aim was to ascertain the efficacy of golimumab compared with placebo in the prevention of atherosclerosis and arterial stiffness in AS . METHODS A r and omized , double-blind , placebo-controlled pilot study was performed in which AS patients were treated with  golimumab ( n = 20 ) and placebo  ( n = 21 ) for 12 months . Patients from the placebo group who failed to achieve a 20 % response to Assessment of SpondyloArthritis international Society criteria ( ASAS20 ) at 6 months received open-label golimumab .  Intima-media thickness ( IMT ) , pulse wave velocity ( PWV ) and augmentation index ( AIx ) were measured at baseline , 6 and 12 months . RESULTS At 6 months , 11/20 ( 55 % ) and 3/21 ( 14 % ) patients from the golimumab and placebo groups achieved an ASAS20 response , respectively ( P = 0.006 ) . There was no significant difference in the change of the vascular parameters between the two groups . In the placebo group , significantly greater progression of the mean IMT [ from 0.51 mm ( S.D. 0.07 ) at baseline to 0.53 mm ( S.D. 0.08 ) at 6 months , P = 0.044 ] and PWV ( from 12.2 m/s ( S.D. 1.6 ) at baseline to 12.6 m/s ( S.D. 1.3 ) , P = 0.028 ] were observed . There was a trend towards progression of the mean IMT in the golimumab group ( P = 0.099 ) but the maximum IMT , PWV and AIx remained unchanged . At 12 months the changes in vascular parameters were similar between the early and delayed ( or no ) golimumab groups . CONCLUSION Uncontrolled inflammation may result in a significant progression in IMT and PWV in patients with AS . Arterial dysfunction may be prevented by golimumab over a period of 6 months , probably because of effective suppression of inflammation . TRIAL REGISTRATION clinical trials.gov ( NCT01212653 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 
    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 examine the characteristics and frequency of disease flares in a cohort of people with AS . Methods . A prospect i ve data set from a r and omized controlled trial ( RCT ) of a probiotic treatment/placebo was utilized to examine disease flares in 134 people with AS . Disease flares were defined as either minor/localized flares ( pain/swelling localized to one area with fatigue and stiffness ) or major/generalized flares ( generalized pain , hot burning joints , muscle spasm , fever , sweating , extreme fatigue and stiffness ) . Results . One hundred and thirty-four people were followed up for 1216 person follow-up weeks and there were 71.4 flares per 100 person-weeks . Of these , 12 were major/generalized flares and 59.4 were minor/localized flares . People who experienced at least one major/generalized flare during the study period had worse disease during flare-free periods in terms of disease activity , impaired function , self-reported night pain and iritis compared with those who did not experience any major/generalized flares during the study . Major/generalized flares lasted for an average of 2.4 weeks ( s.d . 2.7 ) , and were preceded by and followed by a minor/localized flare in 92 % ( 55/60 ) of cases . Conclusion . Seventy per cent of people with AS felt they had a flare in any given week . Those who experienced major/generalized flares appear to have more severe and active disease even during periods when not in flare , compared with those who do not experience major/generalized flares . These results have implication s for the timing of assessment s prior to starting anti-TNF therapy and suggest that the presence of major flares may be helpful in identifying patients with severe disease Objective . Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK . This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and Bath Ankylosing Spondylitis Functional Index ( BASFI ) after 6 months of therapy in 261 patients enrolled in a national prospect i ve observational register . Methods . The British Society for Rheumatology Biologics Register ( BSRBR ) recruited patients starting anti-TNF therapy for AS between 2002 and 2006 . Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months . Covariates included age , gender , disease duration , baseline BASDAI and BASFI , presence of raised inflammatory markers ( defined as twice the upper limit of normal ) and DMARD therapy . Results . The cohort was young ( median age 43 years ) and 82 % were males .  Median baseline BASDAI was 7.6 and BASFI 7.9 . At 6 months , the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U , respectively ; 52 % reached a BASDAI50 . Patients with raised inflammatory markers at the start of therapy had a 0.9-U ( 95 % CI 0.2 , 1.5 ) better improvement in BASDAI compared with those without . Lesser responses were seen in those with higher baseline BASFI scores . Women had a 1.1-U ( 95 % CI 0.3 , 2.0 ) greater improvement in BASFI at 6 months , as did those who were receiving concurrent DMARD therapy [ 0.9 U ( 95 % CI 0.2 , 1.7 ) ] . Conclusions . The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity . Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI , identifying a group of patients who may be more responsive to anti-TNF therapies , although the results were not confined to this group Objectives To assess whether combination therapy with infliximab ( IFX ) plus nonsteroidal anti-inflammatory drugs ( NSAIDs ) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society ( ASAS ) partial remission in patients with early , active axial spondyloarthritis ( SpA ) who were naïve to NSAIDs or received a submaximal dose of NSAIDs . Methods Patients were r and omised ( 2 : 1 ratio ) to receive naproxen ( NPX ) 1000 mg daily plus either IFX 5 mg/kg or placebo ( PBO ) at weeks 0 , 2 , 6 , 12 , 18 and 24 . The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28 . Several other measures of disease activity , clinical symptoms and patient-rated outcomes were evaluated . Treatment group differences were analysed with Fisher exact tests or analysis of covariance . Results A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group ( 61.9 % ; 65/105 ) than in the PBO+NPX group ( 35.3 % ; 18/51 ) at week 28 ( p=0.002 ) and at all other visits ( p<0.05 , all comparisons ) . Results of most other disease activity and patient-reported endpoints ( including Ankylosing Spondylitis Disease Activity Score , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , multiple quality of life measures and pain measures ) showed greater improvement in the IFX+NPX group than the PBO+NPX group , with several measures demonstrating early and consistent improvement over 28 weeks of treatment . Conclusions Patients with early , active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone . NPX alone led to clinical remission in a third of patients Objective : A double blind , r and omised , placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis ( AS ) . Methods : Adult patients with AS at 14 European sites were r and omly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks . The primary efficacy end point was an improvement of at least 20 % in patient reported symptoms , based on the multicomponent Assessment s in Ankylosing Spondylitis ( ASAS ) response criteria ( ASAS 20 ) . Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , acute phase reactants , and spinal mobility tests . Safety was evaluated during scheduled visits . Results : Of 84 patients enrolled , 45 received etanercept and 39 received placebo . Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2 , and sustained differences were evident up to week 12 . Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2 , 4 , and 8 ; reported lower composite and fatigue BASDAI scores ; had lower acute phase reactant levels ; and had improved spinal flexion .  Etanercept was well tolerated . Most adverse events were mild to moderate ; the only between-group difference was injection site reactions , which occurred significantly more often in etanercept patients . Conclusions : Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS Objectives To compare the pharmacokinetics ( PK ) , safety and efficacy of innovator infliximab ( INX ) and CT-P13 , a biosimilar to INX , in patients with active ankylosing spondylitis ( AS ) . Methods Phase 1 r and omised , double-blind , multicentre , multinational , parallel-group study . Patients were r and omised to receive 5 mg/kg of CT-P13 ( n=125 ) or INX ( n=125 ) . Primary endpoints were area under the concentration-time curve ( AUC ) at steady state and observed maximum steady state serum concentration ( Cmax , ss ) between weeks 22 and 30 . Additional PK , efficacy endpoints , including 20 % and 40 % improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria ( ASAS20 and ASAS40 ) , and safety outcomes were also assessed . Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX . Geometric mean Cmax , ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX . The ratio of geometric means was 104.5 % ( 90 % CI 94 % to 116 % ) for AUC and 101.5 % ( 90 % CI 95 % to 109 % ) for Cmax , ss . ASAS20 and ASAS40 responses at week 30 were 70.5 % and 51.8 % for CT-P13 and 72.4 % and 47.4 % for INX , respectively . In the CT-P13 and INX groups more than one adverse event occurred in 64.8 % and 63.9 % of patients , infusion reactions occurred in 3.9 % and 4.9 % , active tuberculosis occurred in 1.6 % and 0.8 % , and 27.4 % and 22.5 % of patients tested positive for anti-drug antibodies , respectively . Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS . CT-P13 was well tolerated , with an efficacy and safety profile comparable to that of INX up to week 30 OBJECTIVE Our aim was to ascertain the efficacy of golimumab compared with placebo in the prevention of atherosclerosis and arterial stiffness in AS . METHODS A r and omized , double-blind , placebo-controlled pilot study was performed in which AS patients were treated with  golimumab ( n = 20 ) and placebo  ( n = 21 ) for 12 months . Patients from the placebo group who failed to achieve a 20 % response to Assessment of SpondyloArthritis international Society criteria ( ASAS20 ) at 6 months received open-label golimumab .  Intima-media thickness ( IMT ) , pulse wave velocity ( PWV ) and augmentation index ( AIx ) were measured at baseline , 6 and 12 months . RESULTS At 6 months , 11/20 ( 55 % ) and 3/21 ( 14 % ) patients from the golimumab and placebo groups achieved an ASAS20 response , respectively ( P = 0.006 ) . There was no significant difference in the change of the vascular parameters between the two groups . In the placebo group , significantly greater progression of the mean IMT [ from 0.51 mm ( S.D. 0.07 ) at baseline to 0.53 mm ( S.D. 0.08 ) at 6 months , P = 0.044 ] and PWV ( from 12.2 m/s ( S.D. 1.6 ) at baseline to 12.6 m/s ( S.D. 1.3 ) , P = 0.028 ] were observed . There was a trend towards progression of the mean IMT in the golimumab group ( P = 0.099 ) but the maximum IMT , PWV and AIx remained unchanged . At 12 months the changes in vascular parameters were similar between the early and delayed ( or no ) golimumab groups . CONCLUSION Uncontrolled inflammation may result in a significant progression in IMT and PWV in patients with AS . Arterial dysfunction may be prevented by golimumab over a period of 6 months , probably because of effective suppression of inflammation . TRIAL REGISTRATION clinical trials.gov ( NCT01212653 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 
    Output:
    