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 Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate , a st and ard treatment for this disease . There is evidence that antitumour necrosis factor alpha ( TNFalpha ) is efficacious in relief of signs and symptoms . We therefore investigated whether infliximab , a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate .  METHODS In an international double-blind placebo-controlled phase III clinical trial , 428 patients who had active rheumatoid arthritis , who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks , were r and omised to placebo ( n=88 ) or one of four regimens of  infliximab  at weeks 0 , 2 , and 6 . Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate ( median 15 mg/week for > or = 6 months , range 10 - 35 mg/wk ) . Patients were assessed every 4 weeks for 30 weeks . FINDINGS At 30 weeks , the American College of Rheumatology ( 20 ) response criteria , representing a 20 % improvement from baseline , were achieved in 53 , 50 , 58 , and 52 % of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks , respectively , compared with 20 % of patients receiving placebo plus methotrexate ( p<0.001 for each of the four infliximab regimens vs placebo ) . A 50 % improvement was achieved in 29 , 27 , 26 , and 31 % of infliximab plus methotrexate in the same treatment groups , compared with 5 % of patients on placebo plus methotrexate ( p<0.001 ) . Infliximab was well-tolerated ; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group . INTERPRETATION During 30 weeks , treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate Objective : To calculate the number needed to treat ( NNT ) and number needed to harm ( NNH ) from the data in rheumatology clinical trials and systematic review s. Methods : The NNTs for the clinical ly important outcome measures in the rheumatology systematic review s from the Cochrane Library , issue 2 , 2000 and in the original r and omised , double blind , controlled trials were calculated . The measure used for calculating the NNT in rheumatoid arthritis ( RA ) interventions was the American College of Rheumatology 20 % improvement or Paulus criteria ; in osteoarthritis ( OA ) interventions , the improvement of pain ; and in systemic sclerosis ( SSc ) interventions , the improvement of Raynaud 's phenomenon . The NNH was calculated from the rate of withdrawals due to adverse events from the treatment . Results : The data required for the calculation of the NNT were available in 15 systematic review s and 11 original articles . For RA interventions , etanercept treatment for six months had the smallest NNT ( 1.6 ; 95 % confidence interval ( CI ) 1.4 to 2.0 ) , whereas leflunomide had the largest NNH ( 9.6 ; 95 % CI 6.8 to 16.7 ) . For OA treatment options , only etodolac and tenoxicam produced significant pain relief compared with placebo ( NNT=4.4 ; 95 % CI 2.4 to 24.4 and 3.8 ; 95 % CI 2.5 to 7.3 , respectively ) . For SSc interventions , none were shown to be efficacious in improving Raynaud 's phenomenon because the 95 % CI of the NNT was infinite . Conclusions : The NNT and NNH are helpful for clinicians , enabling them to translate the results from clinical trials and systematic review s to use in routine clinical practice . Both NNT and NNH should be accompanied by a limited 95 % CI and adjusted for the individual subject 's baseline risk Objective : To compare patient reported measures of function , health related quality of life ( QoL ) , and satisfaction with medication among patients with rheumatoid arthritis ( RA ) treated with methotrexate ( MTX ) , etanercept , or both for up to 1 year . Methods : In a 52 week , double blind , clinical trial , patients with active RA were r and omised to receive etanercept 25 mg twice weekly , methotrexate up to 20 mg weekly , or combination therapy .  The Health Assessment Question naire ( HAQ ) disability index , EuroQoL health status visual analogue scale ( EQ-5D VAS ) , patient global assessment , and patient general health VAS were administered at baseline and weeks 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 48 , and 52 . Satisfaction with the medication was compared at 52 weeks . Results : Of 682 enrolled patients , 522 completed 52 weeks of treatment . Mean improvement from baseline in HAQ score was 0.65 , 0.70 , and 1.0 for MTX , etanercept , and the combination , respectively . The mean percentage and absolute improvement in the HAQ was significantly higher ( p<0.01 ) for combination therapy than for either of the monotherapies . Combination therapy produced significantly more rapid achievement of HAQ ⩽0.5 sustained for 6 months than either of the monotherapies ( p<0.01 ) . Compared with patients receiving monotherapy , those receiving combination therapy achieved a significantly better ( p<0.05 ) health state as measured by the EQ-5D VAS ( mean ( SD ) 63.7 ( 3.2 ) , 66.8 ( 3.2 ) , 72.7 ( 3.1 ) for MTX , etanercept , and the combination , respectively ) . Results were similar for other assessment s ( p<0.01 ) . Patients in combination and etanercept groups were significantly more likely ( p<0.0001 , p = 0.0009 , respectively ) to report satisfaction with the medication . Conclusions : Combination therapy with etanercept and methotrexate improved function , QoL , and satisfaction with the medication significantly more than monotherapy The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa ( TNF-alfa ) monoclonal antibody ( Remicade ) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis ( RA ) . We investigate also the interval necessary to obtain the improvement in both treatment groups . 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0 , 4 , 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab , anti-TNF-alfa monoclonal antibody ( Remicade ) and methotrexate at a stable dose . Patients were assessed by composite clinical score ( DAS 28 ) and C-reactive protein during 22 weeks of therapy . At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity . At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91 % of infliximab-treated patients and 58 % gold treated patients ( p < 0.001 ) . Adverse events were more frequently observed in infliximab-treated patients , but only gold-treated patients discontinued treatment because adverse events ( 2 patients due to proteinuria , 2 patients due to mucocutaneous changes and one patient due to leucopenia ) . The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions ( 23 reactions out of 160 infusions ) ; most of them were mild ( somnolentia and headache ) and transient . Viral infections ( including herpes simplex and zoster ) were more common in patients treated with infliximab and methotrexate . Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment , especially in the first 6 weeks BACKGROUND Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease . This study was undertaken to determine whether the addition of etanercept , a soluble tumor necrosis factor receptor (p75):Fc fusion protein ( TNFR : Fc ) , to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate .  METHODS In a 24-week , double-blind trial , we r and omly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week ( or as low as 10 mg per week for patients unable to tolerate higher doses ) to receive either etanercept ( 25 mg ) or placebo subcutaneously twice weekly while continuing to receive methotrexate . The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity ( ACR 20 ) at 24 weeks . RESULTS The addition of etanercept to methotrexate therapy result ed in rapid and sustained improvement . At 24 weeks , 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria ( P<0.001 ) ; 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria ( for a 50 percent improvement ) ( P<0.001 ) . Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity . The only adverse events associated with etanercept were mild injection-site reactions , and no patient withdrew from the study because of adverse events associated with etanercept . CONCLUSIONS In patients with persistently active rheumatoid arthritis , the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone Objective : To examine the impact of the combination of infliximab plus methotrexate ( MTX ) on the progression of structural damage in patients with early rheumatoid arthritis ( RA ) . Methods : Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy ( ATTRACT ) study , in which 428 patients with active RA despite MTX therapy received placebo with MTX ( MTX-only ) or infliximab 3 mg/kg or 10 mg/kg every ( q ) 4 or 8 weeks with MTX ( infliximab plus MTX ) for 102 weeks . Early RA was defined as disease duration of 3 years or less ; 82 of the 428 patients ( 19 % ) met this definition . Structural damage was assessed with the modified van der Heijde-Sharp score . The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group . Results : The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen . Consistent benefit was seen in the joints of both h and s and feet . Conclusions : Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment . Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity Objective : This r and omized , placebo‐controlled , double‐blind , Phase 1 study assessed the magnitude , onset , and duration of response with intravenous ( i.v . ) and subcutaneous ( s.c . ) adalimumab ( Humira ® , Abbott Laboratories ) combined with methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) despite previous MTX therapy . Methods : Fifty‐four patients were r and omized to two injections of i.v . or s.c . adalimumab ( 1 mg/kg ) or placebo while continuing on MTX ( mean dose , 15.7 mg/week ) . Dosing intervals were determined by the European League Against Rheumatism ( EULAR ) response criteria , and were allowed to range from 1 to 3 months . Efficacy was mainly assessed using the EUL 
    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 Not all patients with rheumatoid arthritis can tolerate or respond to methotrexate , a st and ard treatment for this disease . There is evidence that antitumour necrosis factor alpha ( TNFalpha ) is efficacious in relief of signs and symptoms . We therefore investigated whether infliximab , a chimeric human-mouse anti-TNFalpha monoclonal antibody would provide additional clinical benefit to patients who had active rheumatoid arthritis despite receiving methotrexate .  METHODS In an international double-blind placebo-controlled phase III clinical trial , 428 patients who had active rheumatoid arthritis , who had received continuous methotrexate for at least 3 months and at a stable dose for at least 4 weeks , were r and omised to placebo ( n=88 ) or one of four regimens of  infliximab  at weeks 0 , 2 , and 6 . Additional infusions of the same dose were given every 4 or 8 weeks thereafter on a background of a stable dose of methotrexate ( median 15 mg/week for > or = 6 months , range 10 - 35 mg/wk ) . Patients were assessed every 4 weeks for 30 weeks . FINDINGS At 30 weeks , the American College of Rheumatology ( 20 ) response criteria , representing a 20 % improvement from baseline , were achieved in 53 , 50 , 58 , and 52 % of patients receiving 3 mg/kg every 4 or 8 weeks or 10 mg/kg every 4 or 8 weeks , respectively , compared with 20 % of patients receiving placebo plus methotrexate ( p<0.001 for each of the four infliximab regimens vs placebo ) . A 50 % improvement was achieved in 29 , 27 , 26 , and 31 % of infliximab plus methotrexate in the same treatment groups , compared with 5 % of patients on placebo plus methotrexate ( p<0.001 ) . Infliximab was well-tolerated ; withdrawals for adverse events as well as the occurrence of serious adverse events or serious infections did not exceed those in the placebo group . INTERPRETATION During 30 weeks , treatment with infliximab plus methotrexate was more efficacious than methotrexate alone in patients with active rheumatoid arthritis not previously responding to methotrexate Objective : To calculate the number needed to treat ( NNT ) and number needed to harm ( NNH ) from the data in rheumatology clinical trials and systematic review s. Methods : The NNTs for the clinical ly important outcome measures in the rheumatology systematic review s from the Cochrane Library , issue 2 , 2000 and in the original r and omised , double blind , controlled trials were calculated . The measure used for calculating the NNT in rheumatoid arthritis ( RA ) interventions was the American College of Rheumatology 20 % improvement or Paulus criteria ; in osteoarthritis ( OA ) interventions , the improvement of pain ; and in systemic sclerosis ( SSc ) interventions , the improvement of Raynaud 's phenomenon . The NNH was calculated from the rate of withdrawals due to adverse events from the treatment . Results : The data required for the calculation of the NNT were available in 15 systematic review s and 11 original articles . For RA interventions , etanercept treatment for six months had the smallest NNT ( 1.6 ; 95 % confidence interval ( CI ) 1.4 to 2.0 ) , whereas leflunomide had the largest NNH ( 9.6 ; 95 % CI 6.8 to 16.7 ) . For OA treatment options , only etodolac and tenoxicam produced significant pain relief compared with placebo ( NNT=4.4 ; 95 % CI 2.4 to 24.4 and 3.8 ; 95 % CI 2.5 to 7.3 , respectively ) . For SSc interventions , none were shown to be efficacious in improving Raynaud 's phenomenon because the 95 % CI of the NNT was infinite . Conclusions : The NNT and NNH are helpful for clinicians , enabling them to translate the results from clinical trials and systematic review s to use in routine clinical practice . Both NNT and NNH should be accompanied by a limited 95 % CI and adjusted for the individual subject 's baseline risk Objective : To compare patient reported measures of function , health related quality of life ( QoL ) , and satisfaction with medication among patients with rheumatoid arthritis ( RA ) treated with methotrexate ( MTX ) , etanercept , or both for up to 1 year . Methods : In a 52 week , double blind , clinical trial , patients with active RA were r and omised to receive etanercept 25 mg twice weekly , methotrexate up to 20 mg weekly , or combination therapy .  The Health Assessment Question naire ( HAQ ) disability index , EuroQoL health status visual analogue scale ( EQ-5D VAS ) , patient global assessment , and patient general health VAS were administered at baseline and weeks 2 , 4 , 8 , 12 , 16 , 20 , 24 , 32 , 40 , 48 , and 52 . Satisfaction with the medication was compared at 52 weeks . Results : Of 682 enrolled patients , 522 completed 52 weeks of treatment . Mean improvement from baseline in HAQ score was 0.65 , 0.70 , and 1.0 for MTX , etanercept , and the combination , respectively . The mean percentage and absolute improvement in the HAQ was significantly higher ( p<0.01 ) for combination therapy than for either of the monotherapies . Combination therapy produced significantly more rapid achievement of HAQ ⩽0.5 sustained for 6 months than either of the monotherapies ( p<0.01 ) . Compared with patients receiving monotherapy , those receiving combination therapy achieved a significantly better ( p<0.05 ) health state as measured by the EQ-5D VAS ( mean ( SD ) 63.7 ( 3.2 ) , 66.8 ( 3.2 ) , 72.7 ( 3.1 ) for MTX , etanercept , and the combination , respectively ) . Results were similar for other assessment s ( p<0.01 ) . Patients in combination and etanercept groups were significantly more likely ( p<0.0001 , p = 0.0009 , respectively ) to report satisfaction with the medication . Conclusions : Combination therapy with etanercept and methotrexate improved function , QoL , and satisfaction with the medication significantly more than monotherapy The objective of the paper was compare the effects and tolerability of combined therapy of multiple intravenous infusions of anti-tumour necrosis factor-alfa ( TNF-alfa ) monoclonal antibody ( Remicade ) with methotrexate versus treatment with sodium aurothiomalate and intramuscular depot methylprednisolone in rheumatoid arthritis ( RA ) . We investigate also the interval necessary to obtain the improvement in both treatment groups . 36 patients commencing intramuscular sodium aurothiomalate therapy with intramuscular depot methylprednisolone acetate at weeks 0 , 4 , 8 and 12 in addition to chrysotherapy were compared in retrospective analysis with 32 patients starting with multiple intravenous infusions of infliximab , anti-TNF-alfa monoclonal antibody ( Remicade ) and methotrexate at a stable dose . Patients were assessed by composite clinical score ( DAS 28 ) and C-reactive protein during 22 weeks of therapy . At week 2 and 6 a significantly greater percentage of infliximab-treated than gold-treated RA patients achieved improvement in each clinical measurement of disease activity . At 22 week of treatment moderate and good response according to EULAR criteria was achieved in 91 % of infliximab-treated patients and 58 % gold treated patients ( p < 0.001 ) . Adverse events were more frequently observed in infliximab-treated patients , but only gold-treated patients discontinued treatment because adverse events ( 2 patients due to proteinuria , 2 patients due to mucocutaneous changes and one patient due to leucopenia ) . The higher percentage of adverse events in infliximab-treated patients was caused mainly by the occurrence of infusion reactions ( 23 reactions out of 160 infusions ) ; most of them were mild ( somnolentia and headache ) and transient . Viral infections ( including herpes simplex and zoster ) were more common in patients treated with infliximab and methotrexate . Combination therapy of infliximab and methotrexate is more effective in reducing clinical and biochemical disease activity than gold with methylprednisolone treatment in RA patients during 22 weeks of treatment , especially in the first 6 weeks BACKGROUND Patients treated with methotrexate for rheumatoid arthritis often improve but continue to have active disease . This study was undertaken to determine whether the addition of etanercept , a soluble tumor necrosis factor receptor (p75):Fc fusion protein ( TNFR : Fc ) , to methotrexate therapy would provide additional benefit to patients who had persistent rheumatoid arthritis despite receiving methotrexate .  METHODS In a 24-week , double-blind trial , we r and omly assigned 89 patients with persistently active rheumatoid arthritis despite at least 6 months of methotrexate therapy at a stable dose of 15 to 25 mg per week ( or as low as 10 mg per week for patients unable to tolerate higher doses ) to receive either etanercept ( 25 mg ) or placebo subcutaneously twice weekly while continuing to receive methotrexate . The primary measure of clinical response was the American College of Rheumatology criteria for a 20 percent improvement in measures of disease activity ( ACR 20 ) at 24 weeks . RESULTS The addition of etanercept to methotrexate therapy result ed in rapid and sustained improvement . At 24 weeks , 71 percent of the patients receiving etanercept plus methotrexate and 27 percent of those receiving placebo plus methotrexate met the ACR 20 criteria ( P<0.001 ) ; 39 percent of the patients receiving etanercept plus methotrexate and 3 percent of those receiving placebo plus methotrexate met the ACR 50 criteria ( for a 50 percent improvement ) ( P<0.001 ) . Patients receiving etanercept plus methotrexate had significantly better outcomes according to all measures of disease activity . The only adverse events associated with etanercept were mild injection-site reactions , and no patient withdrew from the study because of adverse events associated with etanercept . CONCLUSIONS In patients with persistently active rheumatoid arthritis , the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than methotrexate alone Objective : To examine the impact of the combination of infliximab plus methotrexate ( MTX ) on the progression of structural damage in patients with early rheumatoid arthritis ( RA ) . Methods : Subanalyses were carried out on data for patients with early RA in the Anti-TNF Therapy in RA with Concomitant Therapy ( ATTRACT ) study , in which 428 patients with active RA despite MTX therapy received placebo with MTX ( MTX-only ) or infliximab 3 mg/kg or 10 mg/kg every ( q ) 4 or 8 weeks with MTX ( infliximab plus MTX ) for 102 weeks . Early RA was defined as disease duration of 3 years or less ; 82 of the 428 patients ( 19 % ) met this definition . Structural damage was assessed with the modified van der Heijde-Sharp score . The changes from baseline to week 102 in total modified van der Heijde-Sharp score were compared between the infliximab plus MTX groups and the MTX-only group . Results : The erosion and joint space narrowing scores from baseline to week 102 in the cohort of patients with early RA decreased significantly in each infliximab dose regimen compared with the MTX-only regimen . Consistent benefit was seen in the joints of both h and s and feet . Conclusions : Infliximab combined with MTX inhibited the progression of structural damage in patients with early RA during the 2 year period of treatment . Early intervention with infliximab in patients with active RA despite MTX therapy may provide long term benefits by preventing radiographic progression and preserving joint integrity Objective : This r and omized , placebo‐controlled , double‐blind , Phase 1 study assessed the magnitude , onset , and duration of response with intravenous ( i.v . ) and subcutaneous ( s.c . ) adalimumab ( Humira ® , Abbott Laboratories ) combined with methotrexate ( MTX ) in patients with active rheumatoid arthritis ( RA ) despite previous MTX therapy . Methods : Fifty‐four patients were r and omized to two injections of i.v . or s.c . adalimumab ( 1 mg/kg ) or placebo while continuing on MTX ( mean dose , 15.7 mg/week ) . Dosing intervals were determined by the European League Against Rheumatism ( EULAR ) response criteria , and were allowed to range from 1 to 3 months . Efficacy was mainly assessed using the EUL 
    Output:
    