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: Objectives To compare efficacy and safety of various doses of tofacitinib , an oral Janus kinase inhibitor , with placebo in patients with active ankylosing spondylitis ( AS , radiographic axial spondyloarthritis ) . Methods In this 16-week ( 12-week treatment , 4-week washout ) , phase II , multicentre , dose-ranging trial , adult patients with active AS were r and omised ( N=51 , 52 , 52 , 52 , respectively ) to placebo or tofacitinib 2 , 5 or 10 mg twice daily . The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20 % improvement ( ASAS20 ) response rate at week 12 . Secondary endpoints included objective measures of disease activity , patient-reported outcomes and MRI of sacroiliac joints and spine . Safety was monitored . Results Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4 % , 27.3 % higher than placebo . Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo ( 80.8 % vs 41.2 % ; p<0.001 ) ; tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo ( 51.9 % and 55.8 % , respectively ; not significant ) . Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo . Objective ( including MRI ) endpoints demonstrated clear dose response . Adverse events were similar across treatment groups with no unexpected safety findings . Dose-dependent laboratory outcome changes returned close to baseline by week 16 . Conclusions Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs , symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications . Trial registration number NCT01786668 OBJECTIVE The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease-modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials . The objective of this multicenter , r and omized , placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS . METHODS Patients were r and omly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0 , 2 , 6 , 12 , and 18 . Efficacy was assessed using the ASsessment in Ankylosing Spondylitis ( ASAS ) International Working Group criteria , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , night pain , patient 's global assessment , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , chest expansion , the M and er enthesis index , the total swollen joint index , the C-reactive protein level , and the Short Form 36 ( SF-36 ) health survey question naire . The primary end point in this study was the proportion of patients with a 20 % improvement response according to the ASAS International Working Group criteria ( ASAS20 responders ) at week 24 . RESULTS Of the 357 patients screened , 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo . After 24 weeks , 61.2 % of patients in the infliximab group were ASAS20 responders compared with 19.2 % of patients in the placebo group ( P < 0.001 ) . Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period . Patients receiving infliximab also showed significant improvements in the BASDAI , BASFI , BASMI , chest expansion , and physical component summary score of the SF-36 . Adverse events were reported by 82.2 % of patients receiving infliximab and by 72.0 % of patients receiving placebo ; however , most adverse events in both treatment groups were mild or moderate in severity . CONCLUSION Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period Objective : To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis ( AS ) using MRI and DXA to monitor its impact on bone . Methods : In this single centre study 42 subjects with active AS were treated with methotrexate and were r and omly assigned , in a ratio of 2:1 , to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks . The primary outcome was improvement in disease activity as shown by the BASDAI at week 30 . MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density . Results : Both therapeutic agents were well tolerated with no dropouts due to adverse events . A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 ( p = 0.017 ) than in the placebo arm , but this was not maintained by week 30 ( p = 0.195 ) , 8 weeks after the last infusion , at which stage disease flares were reported by some subjects . MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group ( p = 0.016 ) . Conclusions : Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI . However , disease flares were reported 8 weeks after the last infusion , indicating that addition of methotrexate failed to extend the infliximab dosing interval BACKGROUND There are few effective treatments for ankylosing spondylitis , which causes substantial morbidity . Because of the central role of tumor necrosis factor alpha in the spondyloarthritides , we performed a r and omized , double-blind , placebo-controlled trial of etanercept , a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein , in patients with ankylosing spondylitis . METHODS Forty patients with active , inflammatory ankylosing spondylitis were r and omly assigned to receive twice-weekly subcutaneous injections of etanercept ( 25 mg ) or placebo for four months . The primary end point was a composite of improvements in measures of morning stiffness , spinal pain , functioning , the patient 's global assessment of disease activity , and joint swelling . Patients were allowed to continue taking nonsteroidal antiinflammatory drugs , oral corticosteriods ( < or = 10 mg per day ) , and disease-modifying antirheumatic drugs at stable doses during the trial . RESULTS Treatment with etanercept result ed in significant and sustained improvement . At four months , 80 percent of the patients in the etanercept group had a treatment response , as compared with 30 percent of those in the placebo group ( P=0.004 ) . Improvements over base-line values for various measures of disease activity , including morning stiffness , spinal pain , functioning , quality of life , enthesitis , chest expansion , erythrocyte sedimentation rate , and C-reactive protein , were significantly greater in the etanercept group . Longitudinal analysis showed that the treatment response was rapid and did not diminish over time . Etanercept was well tolerated , with no significant differences in rates of adverse events between the two groups . CONCLUSIONS Treatment with etanercept for four months result ed in rapid , significant , and sustained improvement in patients with ankylosing spondylitis Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks  ( Q2W ) or  CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus  placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regimens , and in AS and nr-axSpA patients OBJECTIVE The aim of this study was to assess the efficacy and safety of golimumab in Chinese patients with active AS . METHODS Two hundred and thirteen patients were r and omized in a 1:1 ratio to receive either s.c . injections of placebo from weeks 0 to 20 followed by golimumab 50 mg from weeks 24 to 48 ( group 1 , n = 105 ) or golimumab 50 mg from weeks 0 to 48 ( group 2 , n = 108 ) , both every 4 weeks . Placebo crossover occurred at week 24 , while early escape was at week 16 . The primary endpoint was an improvement of at least 20 % in the Assessment of SpondyloArthritis international Society ( ASAS20 ) criteria at week 14 . Major secondary endpoints included week 24 ASAS20 response and week 14 change scores for BASFI and BASMI . RESULTS Golimumab treatment elicited significantly better responses than placebo in week 14 ASAS20 response [ 49.1 % ( 53/108 ) vs 24.8 % ( 26/105 ) , respectively , P < 0.001 ] , week 24 ASAS20 response ( 50.0 % vs 22.9 % , P < 0.001 ) and mean improvements in BASFI ( -1.26 vs 0.11 , P < 0.001 ) and BASMI ( -0.42 vs -0.19 , P = 0.021 ) scores at week 14 . Additionally , golimumab treatment led to significant improvements in the mental and physical components of health-related quality of life ( HRQoL ) and sleep problems at week 24 , all of which were further improved through week 52 . During the 16-week placebo-controlled study period , 31.4 % and 30.6 % of patients had adverse events ( AEs ) in groups 1 and 2 , respectively ; similar AE reporting rates were observed through week 24 ( 34.3 % and 32.0 % ) and among the golimumab-treated patients through week 56 ( 41.2 % ) . CONCLUSION Golimumab significantly reduced clinical symptoms/signs and improved physical function , range of motion and HRQoL in Chinese patients with active AS without unexpected safety concerns . TRIAL REGISTRATION Clinical Trials.gov , NCT01248793 Objective . To evaluate the safety and efficacy of intravenous golimumab ( GOL ) in patients with active ankylosing spondylitis ( AS ) . Methods . In a phase III , r and omized , double-blind , placebo (PBO)-controlled trial , 208 patients were r and omized ( 1:1 ) to intravenous ( IV ) infusions of GOL 2 mg/kg ( n = 105 ) at weeks 0 , 4 , 12 , and every 8 weeks , or PBO ( n = 103 ) at weeks 0 , 4 , and 12 , with crossover to GOL at Week 16 . The primary endpoint was ≥ 20 % improvement from baseline in the Assessment of Sp 
    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: Objectives To compare efficacy and safety of various doses of tofacitinib , an oral Janus kinase inhibitor , with placebo in patients with active ankylosing spondylitis ( AS , radiographic axial spondyloarthritis ) . Methods In this 16-week ( 12-week treatment , 4-week washout ) , phase II , multicentre , dose-ranging trial , adult patients with active AS were r and omised ( N=51 , 52 , 52 , 52 , respectively ) to placebo or tofacitinib 2 , 5 or 10 mg twice daily . The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20 % improvement ( ASAS20 ) response rate at week 12 . Secondary endpoints included objective measures of disease activity , patient-reported outcomes and MRI of sacroiliac joints and spine . Safety was monitored . Results Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4 % , 27.3 % higher than placebo . Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo ( 80.8 % vs 41.2 % ; p<0.001 ) ; tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo ( 51.9 % and 55.8 % , respectively ; not significant ) . Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo . Objective ( including MRI ) endpoints demonstrated clear dose response . Adverse events were similar across treatment groups with no unexpected safety findings . Dose-dependent laboratory outcome changes returned close to baseline by week 16 . Conclusions Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs , symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications . Trial registration number NCT01786668 OBJECTIVE The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease-modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials . The objective of this multicenter , r and omized , placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS . METHODS Patients were r and omly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0 , 2 , 6 , 12 , and 18 . Efficacy was assessed using the ASsessment in Ankylosing Spondylitis ( ASAS ) International Working Group criteria , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , night pain , patient 's global assessment , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , chest expansion , the M and er enthesis index , the total swollen joint index , the C-reactive protein level , and the Short Form 36 ( SF-36 ) health survey question naire . The primary end point in this study was the proportion of patients with a 20 % improvement response according to the ASAS International Working Group criteria ( ASAS20 responders ) at week 24 . RESULTS Of the 357 patients screened , 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo . After 24 weeks , 61.2 % of patients in the infliximab group were ASAS20 responders compared with 19.2 % of patients in the placebo group ( P < 0.001 ) . Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period . Patients receiving infliximab also showed significant improvements in the BASDAI , BASFI , BASMI , chest expansion , and physical component summary score of the SF-36 . Adverse events were reported by 82.2 % of patients receiving infliximab and by 72.0 % of patients receiving placebo ; however , most adverse events in both treatment groups were mild or moderate in severity . CONCLUSION Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period Objective : To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis ( AS ) using MRI and DXA to monitor its impact on bone . Methods : In this single centre study 42 subjects with active AS were treated with methotrexate and were r and omly assigned , in a ratio of 2:1 , to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks . The primary outcome was improvement in disease activity as shown by the BASDAI at week 30 . MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density . Results : Both therapeutic agents were well tolerated with no dropouts due to adverse events . A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 ( p = 0.017 ) than in the placebo arm , but this was not maintained by week 30 ( p = 0.195 ) , 8 weeks after the last infusion , at which stage disease flares were reported by some subjects . MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group ( p = 0.016 ) . Conclusions : Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI . However , disease flares were reported 8 weeks after the last infusion , indicating that addition of methotrexate failed to extend the infliximab dosing interval BACKGROUND There are few effective treatments for ankylosing spondylitis , which causes substantial morbidity . Because of the central role of tumor necrosis factor alpha in the spondyloarthritides , we performed a r and omized , double-blind , placebo-controlled trial of etanercept , a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein , in patients with ankylosing spondylitis . METHODS Forty patients with active , inflammatory ankylosing spondylitis were r and omly assigned to receive twice-weekly subcutaneous injections of etanercept ( 25 mg ) or placebo for four months . The primary end point was a composite of improvements in measures of morning stiffness , spinal pain , functioning , the patient 's global assessment of disease activity , and joint swelling . Patients were allowed to continue taking nonsteroidal antiinflammatory drugs , oral corticosteriods ( < or = 10 mg per day ) , and disease-modifying antirheumatic drugs at stable doses during the trial . RESULTS Treatment with etanercept result ed in significant and sustained improvement . At four months , 80 percent of the patients in the etanercept group had a treatment response , as compared with 30 percent of those in the placebo group ( P=0.004 ) . Improvements over base-line values for various measures of disease activity , including morning stiffness , spinal pain , functioning , quality of life , enthesitis , chest expansion , erythrocyte sedimentation rate , and C-reactive protein , were significantly greater in the etanercept group . Longitudinal analysis showed that the treatment response was rapid and did not diminish over time . Etanercept was well tolerated , with no significant differences in rates of adverse events between the two groups . CONCLUSIONS Treatment with etanercept for four months result ed in rapid , significant , and sustained improvement in patients with ankylosing spondylitis Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks  ( Q2W ) or  CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus  placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regimens , and in AS and nr-axSpA patients OBJECTIVE The aim of this study was to assess the efficacy and safety of golimumab in Chinese patients with active AS . METHODS Two hundred and thirteen patients were r and omized in a 1:1 ratio to receive either s.c . injections of placebo from weeks 0 to 20 followed by golimumab 50 mg from weeks 24 to 48 ( group 1 , n = 105 ) or golimumab 50 mg from weeks 0 to 48 ( group 2 , n = 108 ) , both every 4 weeks . Placebo crossover occurred at week 24 , while early escape was at week 16 . The primary endpoint was an improvement of at least 20 % in the Assessment of SpondyloArthritis international Society ( ASAS20 ) criteria at week 14 . Major secondary endpoints included week 24 ASAS20 response and week 14 change scores for BASFI and BASMI . RESULTS Golimumab treatment elicited significantly better responses than placebo in week 14 ASAS20 response [ 49.1 % ( 53/108 ) vs 24.8 % ( 26/105 ) , respectively , P < 0.001 ] , week 24 ASAS20 response ( 50.0 % vs 22.9 % , P < 0.001 ) and mean improvements in BASFI ( -1.26 vs 0.11 , P < 0.001 ) and BASMI ( -0.42 vs -0.19 , P = 0.021 ) scores at week 14 . Additionally , golimumab treatment led to significant improvements in the mental and physical components of health-related quality of life ( HRQoL ) and sleep problems at week 24 , all of which were further improved through week 52 . During the 16-week placebo-controlled study period , 31.4 % and 30.6 % of patients had adverse events ( AEs ) in groups 1 and 2 , respectively ; similar AE reporting rates were observed through week 24 ( 34.3 % and 32.0 % ) and among the golimumab-treated patients through week 56 ( 41.2 % ) . CONCLUSION Golimumab significantly reduced clinical symptoms/signs and improved physical function , range of motion and HRQoL in Chinese patients with active AS without unexpected safety concerns . TRIAL REGISTRATION Clinical Trials.gov , NCT01248793 Objective . To evaluate the safety and efficacy of intravenous golimumab ( GOL ) in patients with active ankylosing spondylitis ( AS ) . Methods . In a phase III , r and omized , double-blind , placebo (PBO)-controlled trial , 208 patients were r and omized ( 1:1 ) to intravenous ( IV ) infusions of GOL 2 mg/kg ( n = 105 ) at weeks 0 , 4 , 12 , and every 8 weeks , or PBO ( n = 103 ) at weeks 0 , 4 , and 12 , with crossover to GOL at Week 16 . The primary endpoint was ≥ 20 % improvement from baseline in the Assessment of Sp 
    Output:
    