Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE) Full dose, reduced dose or discontinuation of etanercept in rheumatoid arthritis A randomised controlled trial of etanercept and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient-reported Outcomes in Patients with Early Rheumatoid Arthritis Rapid and sustained improvement in health-related quality of life and utility for 72 weeks in patients with ankylosing spondylitis receiving etanercept. Evaluation of Ankylosing Spondylitis Quality of Life questionnaire: responsiveness of a new patient-reported outcome measure. Low doses of etanercept can be effective to maintain remission in ankylosing spondylitis patients Etanercept Increases Bone Mineral Density in Ankylosing Spondylitis, but Does Not Prevent Vertebral Fractures: Results of a Prospective Observational Cohort Study Open-Label Observation of Addition of Etanercept Versus a Conventional Disease-Modifying Antirheumatic Drug in Subjects With Active Rheumatoid Arthritis Despite Methotrexate Therapy in the Latin American Region Cost-effectiveness of etanercept in patients with severe ankylosing spondylitis in Germany. Efficacy and safety of combination etanercept and methotrexate versus etanercept alone in patients with rheumatoid arthritis with an inadequate response to methotrexate: the ADORE study Patient-reported health outcomes in a trial of etanercept monotherapy versus combination therapy with etanercept and methotrexate for rheumatoid arthritis: the ADORE trial Patient-reported outcomes improve with etanercept plus methotrexate in active early rheumatoid arthritis and the improvement is strongly associated with remission: the COMET trial A phase III, multicentre, randomised, double-blind, active-controlled, parallel-group trial comparing safety and efficacy of HD203, with innovator etanercept, in combination with methotrexate, in patients with rheumatoid arthritis: the HERA study Methodological aspects and the interpretation of clinical trial data: lessons from the TEAR trial. 52-week results of the phase 3 randomized study comparing SB4 with reference etanercept in patients with active rheumatoid arthritis A phase 3 randomized, double-blind, multicenter comparative study evaluating the effect of etanercept versus methotrexate on radiographic outcomes, disease activity, and safety in Japanese subjects with active rheumatoid arthritis Comparison of joint destruction between standard- and low-dose etanercept in rheumatoid arthritis from the Prevention of Cartilage Destruction by Etanercept (PRECEPT) study. A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA) Discontinuation of etanercept after achievement of sustained remission in patients with rheumatoid arthritis who initially had moderate disease activity—results from the ENCOURAGE study, a prospective, international, multicenter randomized study Comparison of effectiveness and safety of infliximab, etanercept, and adalimumab in psoriatic arthritis patients who experienced an inadequate response to previous disease-modifying antirheumatic drugs Improved health outcomes with Etanercept versus usual DMARD therapy in an Asian population with established rheumatoid arthritis Assessment of long-term safety and efficacy of etanercept in a 5-year extension study in patients with rheumatoid arthritis.
Objectives Patients with advanced ankylosing spondylitis ( AS ) experience disability because of reduced spinal mobility and pulmonary function impairment . This placebo-controlled study evaluated the effect of etanercept ( ETN ) in patients with advanced AS . Methods A multicentre r and omised double-blind placebo-controlled trial of 12 weeks ' duration was performed . Patients had definite ( modified New York criteria ) , active ( Bath AS Disease Activity Index ( BASDAI ) ≥40 ) , severe ( radiological intervertebral bridges ) AS refractory to non-steroidal anti-inflammatory drugs and were antitumour necrosis factor naive . They were treated with ETN 50 mg once weekly or identical placebo ( PBO ) . Results Of the 95 patients screened , 82 were r and omised to receive ETN ( n=39 ) or PBO ( n=43 ) . At baseline the disease was active ( mean BASDAI 61.0±13.4 , C reactive protein ( CRP ) 20.7±25.5 mg/l ) and severe ( mean Bath AS Metrology Index ( BASMI ) 5.7±1.3 , mSASSS 36.5±20.5 ) ; forced pulmonary vital capacity ( FVC ) was 3.3±0.7 l. Improvement in BASDAI ( normalised net incremental area under the curve between baseline and week 12 , primary end point ) was significantly greater in the ETN group than in the PBO group ( −19.8±16.5 vs −11.0±16.4 , p=0.019 ) . Moreover , at week 12 , ETN gave better results than PBO for the BASDAI ( −26.4±19.7 vs −14.4±19.7 ; p=0.008 ) , total back pain ( −29.2±24.0 vs −14.9±24.0 ; p=0.010 ) , BASFI ( −21.7±17.6 vs −10.1±17.6 ; p=0.004 ) , BASMI ( −0.6±0.6 vs −0.2±0.6 ; p=0.011 ) , CRP level ( −15.7±14.2 vs −1.3±14.2 ; p<0.001 ) and FVC ( + 160±280 ml vs −20±280 ml ; p=0.006 ) . Conclusions ETN has short-term efficacy for patients with advanced AS , as was previously reported for less advanced disease . The efficacy is observed for the main symptoms ( pain ) and on markers of inflammation ( CRP ) , as well as disease severity in terms of spinal mobility and pulmonary function Background The aim of the Dose Reduction or Discontinuation of Etanercept in Methotrexate-Treated Rheumatoid Arthritis Patients Who Have Achieved a Stable Low Disease Activity-State study was to investigate the effect of etanercept ( ETN ) dose maintenance , reduction or withdrawal on patients with rheumatoid arthritis ( RA ) who had already achieved stable low disease activity ( LDA ) on ETN 50 mg+methotrexate ( MTX ) .  Methods Patients with RA ( n=91 ) and stable LDA with ETN 50 mg once weekly (QW)+MTX were included . After 8 weeks with unchanged treatment , 73 patients were r and omised in a double-blind design to ETN 50 mg QW+MTX ( ETN50 ) , ETN 25 mg QW+MTX ( ETN25 ) or placebo QW+MTX ( PBO ) for 48 weeks . Patients who flared were declared failures and treated with open-label ETN50 until week 48 . The primary outcome was the proportion of patients on ETN50 versus PBO who were non-failures after 48 weeks . Results The proportion of non-failure patients was significantly lower with ETN50 ( 52 % ; p=0.007 ) and ETN25 ( 44 % ; p=0.044 ) versus PBO ( 13 % ) . Median time to failure was significantly shorter with PBO ( 6 weeks ) compared with ETN50 ( 48 weeks ; p=0.001 ) and ETN25 ( 36 weeks ; p<0.001 ) . The majority of patients who flared regained LDA with open-label ETN50 quickly . Adverse events were consistent with the known side effect profiles of these medications . Conclusions In patients with established RA who have achieved stable LDA on ETN50+MTX , continuing both is superior to PBO+MTX . Reduced dose ETN was also more effective than PBO in maintaining a favourable response , suggesting that a maintenance strategy with reduced dose ETN may be possible in a number of patients with established RA . Trial registration number NCT00858780 Objective To compare the efficacy of etanercept ( ETN ) and methotrexate ( MTX ) versus MTX monotherapy for remission induction in patients with early inflammatory arthritis . Methods In a 78-week multicentre r and omised placebo-controlled superiority trial , 110 DMARD-naïve patients with early clinical synovitis ( ≥1 tender and swollen joint , and within 3 months of diagnosis ) and either rheumatoid factor , anticitrullinated protein antibodies or shared epitope positive were r and omised 1:1 to receive MTX+ETN or MTX+placebo ( PBO ) for 52 weeks . Injections ( ETN or PBO ) were stopped in all patients at week 52 . In those with no tender or swollen joints ( NTSJ ) for > 26 weeks , injections were stopped early . If patients had NTSJ > 12 weeks after stopping the injections , MTX was weaned . The primary endpoint was NTSJ at week 52 . Results No statistically significant difference was seen for the primary endpoint ( NTSJ at week 52 ( 32.5 % vs 28.1 % [ adjusted OR 1.32 ( 0.56 to 3.09 ) , p=0.522 ] ) in the MTX+ETN and MTX+PBO groups , respectively ) . The secondary endpoints did not differ between groups at week 52 or 78 . Exploratory analyses showed a higher proportions of patients with DAS28-CRP<2.6 in the MTX+ETN group at week 2 ( 38.5 % vs 9.2 % , adjusted OR 8.87 ( 2.53 to 31.17 ) , p=0.001 ) and week 12 ( 65.1 % vs 43.8 % , adjusted OR 2.49 ( 1.12 to 5.54 ) , p=0.026 ) . Conclusions In this group of patients with early inflammatory arthritis , almost a third had no tender , swollen joints after 1 year . MTX+ETN was not superior to MTX monotherapy in achieving this outcome . Clinical responses , however , including DAS28-CRP<2.6 , were achieved earlier with MTX+ETN combination therapy . Trial registration number The EMPIRE trial is registered on the following trial registries : Eudract-2005 - 005467 - 29 ; IS RCT N 55428162 ( http://www.controlled-trials.com/IS RCT N55428162/EMPIRE ) . The full trial protocol can be obtained from the corresponding author Objective . An analysis of a clinical trial to assess the effects of treatment reduction and withdrawal on patient-reported outcomes ( PRO ) in patients with early , moderate to severe rheumatoid arthritis ( RA ) who achieved 28-joint Disease Activity Score ( DAS28 ) low disease activity ( LDA ) or remission with etanercept ( ETN ) plus methotrexate ( MTX ) therapy . Methods . During treatment induction , patients received open-label ETN 50 mg weekly plus MTX for 52 weeks . In the reduced-treatment phase , patients with DAS28-erythrocyte sedimentation rate ( ESR ) ≤ 3.2 at Week 39 and DAS28-ESR < 2.6 at Week 52 in the open-label phase were r and omized to double-blind treatment with ETN 25 mg plus MTX , MTX , or placebo ( PBO ) for 39 weeks ( weeks 0–39 ) . In the third phase , patients who achieved DAS28 remission ( DAS28-ESR < 2.6 ) or LDA ( 2.6 ≤ DAS28-ESR ≤ 3.2 ) at Week 39 in the double-blind phase had all treatment withdrawn and were observed for an additional 26 weeks ( weeks 39–65 ) . Results . Of the 306 patients enrolled , 193 were r and omized in the double-blind phase and 131 participated in the treatment-withdrawal phase . After reduction or withdrawal of ETN 50 mg/MTX , patients reduced to ETN 25 mg/MTX experienced slight , nonsignificant declines in the majority of PRO measures , whereas switching to PBO or MTX alone caused significant declines . Presenteeism and activity impairment scores were significantly better in the ETN reduced-dose group versus MTX monotherapy and PBO at Week 39 ( p ≤ 0.05 ) . Conclusion . In patients with early RA who achieved remission while receiving full-dose ETN/MTX , continuing combination therapy at a lower dose did not cause a significant worsening of PRO response , but switching to MTX alone or PBO did . Clinical Trials.gov identifier : NCT00913458 OBJECTIVE To examine the longterm effect of etanercept ( ETN ) therapy on health-related quality of life ( HRQOL ) and utility in patients with ankylosing spondylitis . METHODS Patients completing a 24-week placebo-controlled trial were continued on ETN in a 72-week open-label extension study . Short Form-36 ( SF-36 ) , EuroQOL-5D ( EQ-5D ) , and EuroQOL visual analog scale ( EQ-VAS ) scores were collected at open-label baseline and every 12 weeks thereafter . Mental and physical component scores ( MCS and PCS ) of the SF-36 , EQ-5D and SF-6D utility scores , and quality -adjusted life-years ( QALY ) were calculated . RESULTS 257 patients [ 129 previous placebo ( PLA ) and 128 ETN recipients ] enrolled in this open-label extension study , and 85 % completed the 72-week followup . PCS , EQ-5D and SF-6D utilities , and EQ-VAS were significantly lower at open-label baseline in the previous PLA group ( PLA/ETN group ) than in the previous ETN group ( ETN/ETN group ; all p < 0.001 ) . At week 12 , PCS and MCS , EQ-5D and SF-6D utility scores , and EQ-VAS were similar in the PLA/ETN and ETN/ETN groups . As expected , mean change in EQ-5D in the PLA/ETN group was significantly greater than that for SF-6D ( 0.18 vs 0.06 ; p < 0.0001 ) . HRQOL and utility improvements were maintained in both groups for up to 72 weeks . The average 72-week QALY gain per person in the PLA/ETN group was 0.24 and 0.10 for EQ-5D and SF-6D , respectively . CONCLUSION Patients continuing ETN therapy sustained HRQOL and utility improvements attained during the original PLA-controlled trial . Patients previously taking PLA  showed rapid and sustained improvements in HRQOL and utility and substantial QALY gain with ETN therapy OBJECTIVE To determine the responsiveness and minimal important change ( MIC ) of Evaluation of Ankylosing Spondylitis Quality of Life ( EASi-QoL ) , a reliable and valid patient-reported measure of AS-specific quality of life with four domains : physical function ( PF ) , disease activity ( DA ) , emotional well-being ( EWB ) and social participation ( SP ) . METHODS A total of 1000 UK AS patients received a postal question naire including EASi-QoL. Comparative responsiveness of EASi-QoL was assessed against measures reflecting similar health domains in patients self-reporting an improvement in their AS-specific health at 6 months on a health transition question . Effect size ( ES ) statistics were calculated for all measures and MIC was determined for EASi-QoL. Comparative responsiveness was determined in a r and omized trial of AS patients receiving etanercept ( ETN ) 50 mg weekly or SSZ 3 g daily . RESULTS Of 470 patients , 80 responding at 6 months reported health improvement . Responsiveness ( ES ) for EASi-QoL domains was superior or similar to comparator measures : DA 0.72 vs BASDAI 0.58 ; SP 0.52 vs SF-36 social functioning 0.29 ; PF 0.32 vs BASFI 0.28 and SF-36 PF 0.24 ; EWB 0.40 vs HADS-anxiety 0.13 , HADS-depression 0.21 and SF-36 mental health 0.35 . ES for the ASQoL was 0.40 . Superior ES was seen in those improving somewhat . In the r and omized trial , all EASi-QoL domains had superior responsiveness to comparator measures following ETN treatment . Following SSZ treatment , all EASi-QoL domains were highly responsive , but BASDAI and BASFI was more responsive than EASi-QoL(DA ) and ( PF ) , respectively . CONCLUSION In patients reporting improvement during routine clinical practice or following treatment with ETN or SSZ , EASi-QoL domains have superior or comparable responsiveness than comparable measures We wanted to do a prospect i ve open-label study to evaluate if ankylosing spondylitis ( AS ) patients in clinical remission with twice weekly etanercept ( ETN ) 25 mg therapy could be changed to weekly regimen or even to every other week regimen without increased dose for injection . Thirty-eight AS patients self-administered 25 mg of ETN ( Wyett ) subcutaneously . According to the protocol , patients who were in clinical partial remission with twice weekly ETN 25 mg at week 12 and 16 changed to a weekly regimen without a change of the dose . If clinical remission , despite the reduction of the dose , persists at week 24 and 28 , patients changed to an every-other-week regimen , continuing with this administration schedule for the entire duration of the study if at week 36 and 46 clinical remission was maintained . At the end of the study , 18 patients ( 47 % ) were still in remission , 4 ( 10 % ) with a weekly regimen , and 14 ( 37 % ) with an every-other-weekly regimen . Our study indicates that a consistent percentage of subjects with AS , treated with ETN 25 mg twice weekly , achieved clinical remission within the first 3 months of therapy , and also , a substantial percentage of these patients maintains the partial remission with an every other week regimen Objective . Ankylosing spondylitis ( AS ) is characterized by chronic inflammation leading to ankylosis , but also to low bone mineral density ( BMD ) and vertebral fractures ( VFx ) . Treatment with tumor necrosis factor-α blockers decreases inflammation and has shown to be effective in increasing BMD . We studied the effects of etanercept ( ETN ) on BMD and VFx in patients with AS after 2 years of treatment . Further , we studied changes in bone turnover markers and radiological damage . Methods . Patients with active AS , treated with ETN for 2 years , were included . BMD lumbar spine and hip were measured at baseline and after 2 years , as well as radiological damage ( modified Stoke Ankylosing Spondylitis Spinal Score with the addition of the thoracic spine ) , VFx ( Genant method ) , and change in bone turnover markers . Results . Forty-nine patients with AS were included . After 2 years of ETN , hip BMD increased by 2.2 % ( p = 0.014 ) and lumbar spine BMD by 7.0 % ( p < 0.001 ) . The Bath Ankylosing Spondylitis Disease Activity Index decreased significantly ( p < 0.001 ) , as well as C-reactive protein and erythrocyte sedimentation rate ( p < 0.001 ) . Despite ETN therapy , the number of patients with VFx more than doubled ( from 6 to 15 patients , p = 0.003 ) . Also , the radiological damage increased significantly over time ( from 12.1 to 18.5 , p < 0.001 ) ; however , no significant change in bone turnover markers was found . Conclusion . This prospect i ve longitudinal observational cohort study showed that after 2 years of ETN , BMD of the hip and spine increased significantly , but the number of patients with VFx and the severity of VFx increased as well . Besides that , radiological progression , including the thoracic spine , increased significantly . Thus , the favorable bone-preserving effect is accompanied by unfavorable outcomes on VFx and radiological damage Background Previous global studies examined etanercept ( ETN ) + methotrexate ( MTX ) for treatment of rheumatoid arthritis ( RA ) , but included few subjects from Latin America . Objective The objective of this study was to compare the safety and efficacy of ETN + MTX versus a st and ard-of-care disease-modifying antirheumatic drug ( DMARD ) + MTX in Latin American subjects with moderate to severe active RA despite MTX therapy . Methods This open-label , active-comparator study ( NCT00848354 ) r and omized subjects 2:1 to ETN 50 mg/wk + MTX or investigator-selected DMARD ( sulfasalazine or hydroxychloroquine ) + MTX ( ETN + MTX , n = 281 ; DMARD + MTX , n = 142 ) . The primary end point was the proportion achieving American College of Rheumatology ( ACR ) 50 at week 24 . Secondary end points included ACR20/70 , disease activity score ( DAS ) 28 measures , and mean change in modified total Sharp score . Patient-reported outcomes were the Health Assessment Question naire , 36-item Short-Form , Hospital Anxiety and Depression Scale , Work Productivity and Activity Impairment : RA ( WPAI : RA ) , and Caregiver Burden and Re source Utilization . Statistical analyses were stratified by country ; & khgr;2 test and analysis of covariance were used . Adverse events were monitored . Results More subjects achieved ACR50 at week 24 with ETN + MTX versus DMARD + MTX ( 62 % vs 23 % , respectively ) , in addition to secondary end points ( P < 0.0001 for all ) ; mean change in modified total Sharp score was lower for the ETN + MTX group ( 0.4 vs 1.4 , respectively ; P = 0.0270 ) . Improvements in patient-reported outcomes favored ETN + MTX for Health Assessment Question naire , 36-item Short-Form , Hospital Anxiety and Depression Scale for depression , WPAI : RA , and Caregiver Burden and Re source Utilization emergency department visits for RA ( P < 0.01 ) . Overall , adverse events were similar between the groups ( 69 % vs 68 % , ) ; serious adverse events were also similar ( 4 % vs 1 % ) . The rate of overall infections was higher with ETN + MTX ( 38 % ) than DMARD + MTX ( 22 % , P ⩽ 0.001 ) . Conclusions Consistent with published global data among RA patients with inadequate response to MTX  , adding ETN to MTX demonstrated better efficacy than adding  one  other conventional DMARD to MTX .  No new safety issues were observed . ETN + MTX provided favorable benefit-risk profile among RA patients from LA region OBJECTIVES To estimate the cost-effectiveness of etanercept ( ETN ) plus usual care ( including NSAIDs ) compared with usual care alone ( including NSAIDs ) in patients with severe AS in Germany . METHODS A mathematical model previously applied to the UK was adapted using re source use and cost data ( for 2007 ) from the national data base of the German Collaborative Arthritis Centres . Social health insurance ( SHI ) and societal perspectives were analysed . Assumptions on initial response and changes in health-related quality of life were based on Phase III r and omized controlled trials . Initial treatment response according to British Society for Rheumatology guidelines were assumed as a conservative estimate in the German context . Long-term disease progression was based on the available literature . Incremental cost-effectiveness ratios ( ICERs ) were expressed as euros/ quality -adjusted life year ( QALY ) , for a cohort of 1000 patients over 25 years . Sensitivity analyses explored uncertainty in results . RESULTS In the base case , ETN plus usual care ( including NSAIDs ) yielded 1475 more QALYs at an additional cost of € 80,827,668 ( SHI ) or € 32,657,590 ( societal ) leading to an ICER of € 54,815/QALY and € 22,147/QALY , respectively . Over a shorter time horizon of 10 years , the ICERs were € 59,006 and € 29,815 for SHI and societal viewpoints , respectively . Assumptions having the largest impact on results included withdrawal rates from ETN , quality of life , disease costs and initial response . CONCLUSIONS Cost-effectiveness for ETN in patients with severe AS in Germany differs according to the cost perspective . Study estimates were higher than in the UK but comparable with reported cost-effectiveness of anti-TNF treatments in patients with RA in Germany Objective : To evaluate the efficacy and safety of etanercept ( ETN ) monotherapy compared with combination ETN and methotrexate ( MTX ) treatment in patients with rheumatoid arthritis who had an inadequate response to MTX monotherapy . ( The response was defined by the presence of Disease Activity Score-28 joint count ( DAS28 ) ⩾3.2 or a combination of ⩾5 swollen joints , ⩾5 painful joints and erythrocyte sedimentation rate ⩾10 mm/h . ) Methods : Patients with active rheumatoid arthritis taking MTX ⩾12.5 mg/week for ⩾3 months were included in this 16 week , r and omised , open-label study . Patients were r and omly assigned to either ETN ( 25 mg subcutaneous injection twice weekly ) added to the baseline dose of MTX or ETN monotherapy . Results : 315 patients were r and omised to ETN ( n = 160 ) or ETN plus MTX ( n = 155 ) . The primary end point , DAS28 ( 4 ) improvement of > 1.2 units , was achieved by 72.8 % and 75.2 % of patients treated with ETN and those treated with ETN plus MTX , respectively , with no significant difference ( p = 0.658 ) between the two groups . The European League Against Rheumatism response criteria of good or moderate response was attained by 80.0 % of patients in the ETN group and by 82.4 % of patients in the ETN plus MTX  group . American College of Rheumatology 20 % , 50 % and 70 % response rates achieved by both groups were also similar : 71.0 % v 67.1 % , 41.9 % v 40.1 % and 17.4 % v 18.4 % , respectively . The rates of adverse and serious adverse events were similar between the treatment groups . Conclusion : Both the addition of ETN to MTX and the substitution of ETN for MTX in patients with rheumatoid arthritis who had an inadequate response to MTX  result ed in substantial improvements in clinical signs and symptoms and were generally well-tolerated treatment strategies for improving clinical signs and symptoms of rheumatoid arthritis Objectives : This study assessed the relative efficacy of etanercept ( ETN ) or etanercept and methotrexate ( ETN+MTX ) for patients with rheumatoid arthritis ( RA ) who had an unsatisfactory response to MTX  , using patient-reported outcomes ( PROs ) of function , pain , general health , disease activity and morning stiffness . Methods : The PROs were secondary assessment s in a 16-week , prospect i ve , r and omised , parallel-group study conducted at 60 European centres . Patients with RA were r and omly assigned either to monotherapy with ETN or combination therapy with ETN+MTX . PRO instruments administered included the Stanford Health Assessment Question naire , the pain visual analogue scale , the EuroQoL assessment of current health state ( EQ-5D ) , the EQ-5D visual analogue scale , a patient global assessment of disease activity and an assessment of morning stiffness . Treatment groups were compared by percentage of patients within clinical ly meaningful categories . The primary endpoint for all PROs was comparison of mean improvement from baseline to week 16 between ETN and ETN+MTX groups . Results : Three hundred and fifteen patients were r and omised to ETN or ETN+MTX . Both treatment arms had similar Health Assessment Question naire Disability Index DI , EQ-5D , patient global assessment of disease activity , pain or morning stiffness scores and improvement from baseline to week 16 . Conclusions : For patients with active RA and intolerance or unsatisfactory response to MTX  , substituting ETN for MTX and adding ETN to MTX are both effective ways of reducing disability , pain , disease activity , morning stiffness , and improving general health Objectives : To compare the effects of etanercept ( ETN ) 50 mg once weekly plus methotrexate ( MTX ) versus MTX alone on patient-reported outcomes ( PROs ) and the relationship between remission and PRO improvement . Methods : In this double-blind , r and omised clinical trial ( COMET ) , PROs included : the Health Assessment Question naire ( HAQ ) , EuroQoL health status , fatigue and pain visual analogue scales , Hospital Anxiety and Depression Scale , and Medical Outcomes Short-Form-36 . Mean changes from baseline were analysed by analysis of covariance using the last observation carried forward method . Results from week 52 are presented . Results : Most PROs demonstrated significantly greater improvements with ETN+MTX than MTX alone , including physical functioning , pain , fatigue and overall health status . A significantly greater improvement in HAQ score was observed in the ETN+MTX than the MTX group ( −1.02 vs −0.72 ; p<0.001 ) and a greater proportion reached the minimal clinical ly important difference of 0.22 ( 88 % vs 78 % ; p<0.006 ) . The relationship between PRO score and clinical status indicated that improvement was greatest among patients achieving remission . Conclusions : Early treatment with ETN+MTX leads to significantly greater improvements in multiple dimensions of PROs than MTX alone . The close relationship between disease activity and PRO improvement suggests that early treatment , with remission as a goal , should maximise the chance of restoring normal functioning and Objectives To evaluate equivalence in efficacy for rheumatoid arthritis ( RA ) and compare the safety of the biosimilar HD203 with innovator etanercept ( ETN ) plus methotrexate ( MTX ) ( Clinical Trials.gov NCT01270997 ) . Methods Patients with active RA received 25 mg HD203 or ETN subcutaneously twice-weekly with MTX for 48 weeks in a phase III , multicentre , r and omised , double-blind , parallel-group design . The primary end point was the proportion of patients achieving  the American College of Rheumatology 20 % response ( ACR20 ) at week 24 for per- protocol study completer set ( PPS ) . Secondary end points included ACR response criteria , ACRn , European League against Rheumatism ( EULAR ) response , change in Disease Activity Score 28 ( DAS28 ) , patient-reported outcomes , safety and immunogenicity . Results Of the 294 r and omised patients ( HD203 , n=147 ; ETN , n=147 ) , 233 comprised the 24-week PPS ( n=115 and 118 , respectively ) . ACR20 at week 24 was achieved by 83.48 % and 81.36 % of PPS patients , respectively , demonstrating equivalent efficacy within predefined margins of ±20 % ( treatment difference 2.12 % , 95 % CI −7.65 % to 11.89 % ) . Outcomes for secondary end points were consistent with the primary efficacy findings . Groups were comparable for overall incidences of treatment-emergent ( all-causality ) adverse events ( AEs )  ( HD203 113 ( 76.9 % ) vs ETN 114 ( 78.1 % ) ( p=0.804 ) ) , adverse drug reactions , serious AEs and discontinuations due to AEs . Few patients ( HD203 , n=8 ; ETN , n=3 ) tested positive for anti-drug antibodies . Conclusion The study met the primary objective of demonstrating equivalent efficacy of HD203 and ETN . HD203 was well tolerated , with safety comparable with ETN in this population of patients with RA . Trial registration number NCT01270997 ; Results The approach to treatment of RA has evolved substantially in recent years with the introduction of highly effective novel therapies that have result ed in new treatment paradigms , such as treat-to-target and the treatment of patients earlier in their disease course [ 1 , 2 ] . Clinicians are very interested in studies that compare the effectiveness of medications that could help them achieve optimal treatment outcomes for their patients . Extrapolation of the results of such studies into clinical practice depends on accurate assessment of data from the clinical trials . This assessment has become increasingly challenging as study design s have become increasingly complex , with multiple arms and changes in treatments over the course of a trial . There are many methods to analyse a given set of data ; with the same data set , depending on the method of analysis , different conclusions can be reached . To help st and ardize this process , a European League Against Rheumatism (EULAR)/ACR committee created guidelines on reporting data from clinical trials [ 3 ] . The complexities of this analysis are illustrated by a recent example . The R and omized Comparative Effectiveness Study of Oral Triple Therapy versus Etanercept plus Methotrexate in the Early , Aggressive Rheumatoid Arthritis ( TEAR ) trial was design ed to address two important clinical questions : ( i ) is it better to intensively treat all early RA patients with multiple DMARDs  , or reserve this treatment only for those who do not appropriately respond to MTX monotherapy ? and ( ii ) is the combination therapy of MTX plus etanercept ( ETN ) superior to triple combination therapy of MTX , SSZ and HCQ ( TT ) , either initially or after insufficient efficacy of MTX at 6 months ? [ 4 ] . Patients with early RA were r and omly assigned to receive MTX monotherapy , MTX plus ETN or TT . At 6 months , patients treated with MTX monotherapy who did not achieve DAS28 < 3.2 were stepped up to add either ETN or move to TT and treated for 102 weeks . The primary outcome , by the protocol , was the area under the curve ( AUC ) of DAS28 from weeks 48 to 102 . Although many of the items suggested by a joint EULAR/ACR committee on reporting disease activity in clinical trials of patients [ 3 ] were reported , several facets of the methods of data analysis need to be fully understood in order to establish whether the reader concurs with the authors ’ conclusions that this study showed no difference in clinical outcomes at 2 years between patients initially treated with MTX plus ETN or TT . The data reported were an observed analysis only for patients who continued in the trial from week 48 to 102 patients had to have done well clinical ly and not had a significant adverse event to remain in the study through week 48 . A more traditional statistical analysis , such as a nonresponder imputation or last observation carried forward from day 0 to week 102 might have given different results . The first question posed , whether it is more effective to start either combination or MTX monotherapy , was not answered ; the results are not presented for those patients initially treated with MTX  who achieved DAS28 < 3.2 at week 26 and then continued to week 102 . The primary outcome reported in the manuscript was an observed group analysis of change in the mean DAS28-ESR from week 48 to 102 and not the AUC of the DAS28 during this time period . The authors stated that their statistical analysis plan was confirmed by their secondary analyses , which did include non-responder imputation and last observation carried forward . However , these analyses were also performed only on patients in the study from week 48 to 102 . In addition to design and statistical considerations , some of the data can be interpreted differently from the authors , and this might be worth some further examination . For instance , the authors reported that there was no difference in the change in DAS28 , or other clinical measures , between the patient groups studied . However , there was a treatment difference at week 102 between the ETN and TT groups for ACR70 ( 18.2 vs 11.3 % , P = 0.02 ) . This would suggest that ETN plus MTX was more effective in achieving a profound response . This difference in profound response may have led to the significant difference in radiographic progression reported with ETN and MTX treatment vs TT at week 102 . The radiographic difference was noted despite the fact that X-rays were not done in patients who withdrew early ; in other studies , results at the time of exit have been extrapolated to the final endpoint to allow comparison . In this case , radiological data are only in those observed or study completers ; by definition , such patients usually fare quite well and patients who do well have less progression of joint damage . Initial TT and initial MTX monotherapy with step-up had similar ACR20/50/70 response rates at 2 years , Abstract Objective To compare the 52-week efficacy and safety of SB4 [ an etanercept biosimilar ] with reference etanercept ( ETN ) in patients with active RA . Methods In a phase 3 , r and omized , double-blind , multicentre study , patients with moderate to severe RA despite MTX treatment were r and omized to receive 50 mg/week of s.c . SB4 or ETN up to week 52 . Efficacy assessment s included ACR response rates , 28-joint DAS , Simplified and Clinical Disease Activity Indices and changes in the modified total Sharp score ( mTSS ) . Safety and immunogenicity were also evaluated . Results A total of 596 patients were r and omized to receive either SB4 ( n = 299 ) or ETN ( n = 297 ) and 505 ( 84.7 % ) patients completed 52 weeks of the study . At week 52 , the ACR20 response rates in the per- protocol set were comparable between SB4 ( 80.8 % ) and ETN ( 81.5 % ) . All efficacy results were comparable between the two groups and they were maintained up to week 52 . Radiographic progression was also comparable and the change from baseline in the mTSS was 0.45 for SB4 and 0.74 for ETN . The safety profile of SB4 was similar to that of ETN and the incidence of anti-drug antibody development up to week 52 was 1.0 and 13.2 % in the SB4 and ETN groups , respectively . Conclusion Efficacy including radiographic progression was comparable between SB4 and ETN up to week 52 . SB4 was well tolerated and had a similar safety profile to that of ETN . Trial registration number Clinical Trials.gov NCT01895309 , EudraCT 2012 - 005026 - Objectives The aim of this phase 3 , double-blind study was to compare the radiographic and clinical effects of etanercept ( ETN ) versus methotrexate ( MTX ) over 52 weeks in Japanese subjects with active rheumatoid arthritis . Methods The study population comprised 550 subjects with inadequate response to ≥1 disease-modifying anti-rheumatic drugs who were r and omized to treatment groups of ETN 25 mg twice weekly ( BIW ; n = 182 ) , ETN 10 mg BIW ( n = 192 ) ,  or MTX  ( ≤8.0 mg/week ; n = 176 ) . Results Of the 550 subjects initially enrolled in the three treatment groups , 21.6 % discontinued the study ; a significantly higher proportion of those who withdrew from the study due to lack of efficacy were in the MTX ( 21.6 % ) group compared with the ETN 25 mg ( 3.3 % ) and ETN 10 mg ( 6.8 % ) groups ( P < 0.001 ) . Mean change from baseline in the modified total Sharp score at week 52 ( primary endpoint ) was significantly lower in the ETN 25 mg [ 3.33 ; st and ard error ( SE ) , 0.73 ] and ETN 10 mg ( 5.19 ; SE 0.93 ) groups than in the MTX group ( 9.82 ; SE 1.16 ; P < 0.0001 vs. either ETN group ) . Compared with subjects receiving MTX , significantly higher percentages of subjects treated with ETN 25 and 10 mg achieved American College of Rheumatology ( ACR ) ACR20 and ACR50 response rates at all time points ( P < 0.01 ) . ETN was well-tolerated , with no unexpected safety findings . Conclusions ETN 25 mg BIW and ETN 10 mg BIW slowed radiographic progression and improved clinical outcomes more effectively than MTX in this Japanese population OBJECTIVE To evaluate the prevention of joint destruction and clinical efficacy of low-dose etanercept ( ETN ) ( 25 mg/week ) compared with st and ard-dose ETN ( 50 mg/week ) in RA . METHODS In this prospect i ve , r and omized , open-label study , 70 patients were assigned to receive  ETN at either 50 or 25 mg/week for 52 weeks . The primary endpoint was the variation in modified total Sharp score ( mTSS ) , and secondary endpoints were variations in disease activity score in 28 joints ( DAS-28 ) , modified HAQ and adverse event rate . Values of mTSS were calculated at baseline and after 52 weeks . Non-progression was estimated as ΔmTSS ≤0.5 , and the non-progression rate was compared between groups . RESULTS Mean values at baseline were as follows : disease duration 9.2 years ; DAS-28 5.45 ; and annual progression of mTSS 26.1 . No significant differences in background were seen between groups . At 52 weeks , the non-progression rate was significantly less in the 25 mg/week group ( 36.7 % ) than in the 50 mg/week group ( 67.7 % ) ( P = 0.041 ) . Mean ΔmTSS was higher at 25 mg/week ( 1.03 ) than at 50 mg/week ( -0.13 ) . DAS-28 was significantly improved at 4 weeks , and the effect of treatment lasted for 52 weeks in both groups . No differences in adverse event rates were seen between groups . CONCLUSION Low-dose ETN is not inferior to st and ard-dose ETN in terms of effects on clinical manifestations . However , in terms of the radiographic non-progression rate , the effects of low-dose ETN may be inferior to the effects of st and ard-dose ETN . TRIAL REGISTRATION UMIN Clinical Trials Registry , http://www.umin.ac.jp/ctr/ , UMIN000001798 Background Rheumatoid arthritis ( RA ) is a chronic inflammatory arthritis , with significant impact on quality of life and functional status . Whilst biologic disease modifying anti-rheumatic drugs ( bDMARD ) such as tumour necrosis factor-inhibitor ( TNFi ) agents have revolutionised outcomes in RA , early diagnosis with immediate conventional therapy , titrated in a treat to target approach is also associated with high remission rates . The main aim of the VEDERA study ( Very Early versus Delayed Etanercept in Rheumatoid Arthritis ) is to assess the depth of remission , sustainability of remission and immunological normalisation induced by very early TNFi with etanercept ( ETN ) or st and ard of care + /- delayed ETN . Methods / Design VEDERA is a pragmatic , phase IV single-centre open-label r and omised superiority trial of 120 patients with early , treatment-naive RA . Patients will be r and omised 1:1 to first-line ETN and methotrexate ( MTX ) or MTX with additional synthetic disease modifying anti-rheumatic drugs ( sDMARDs ) according to a treat to target ( TT ) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved . Participants will have regular disease activity assessment s and imaging evaluation including musculoskeletal ultrasound and MRI . The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks , following either treatment strategy . In addition , the participants are invited to take part in a cardio-vascular sub- study ( Coronary Artery Disease in RA , CADERA ) , which aims to identify the incidence of cardiovascular abnormalities in early RA . Discussion The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission , in comparison to conventional therapy . Trial registration NCT02433184 , Abstract Objectives : To investigate the efficacy and safety of etanercept ( ETN ) in patients with rheumatoid arthritis ( RA ) with moderate disease activity and the possibility to discontinue ETN  after achieving remission . Methods : Multicenter , r and omized , and open-label study was conducted in Japan and Korea . RA patients ( disease duration < 5 years ) with moderate disease activity despite methotrexate ( MTX ) treatment were allocated to either MTX or ETN + MTX ( Period 1 ) for 12 months . Patients who achieved sustained remission  defined as  DAS28  < 2.6 at both 6 and 12 months in the ETN + MTX group , were r and omized to either continue or discontinue ETN for 12 months ( Period 2 ) . Results : A total of 222 patients were enrolled in Period 1 and clinical remission was achieved in 106/157 ( 67.5 % ) and 5/28 ( 17.9 % ) patients in the ETN + MTX and MTX groups , respectively . In Period 2 , sixty-seven patients were r and omized and finally 28/32 ( 87.5 % ) and 15/28 ( 53.6 % ) patients who continued or discontinued  ETN maintained clinical remission . Baseline disease activity and the presence of comorbid diseases influenced the maintenance of remission after ETN discontinuation . Conclusions : ETN + MTX was efficient for RA patients with moderate disease activity into remission . After achieving sustained remission , a half of the patients who discontinued ETN could maintain remission for 1 year The aim of this study is to compare effectiveness and safety of Infliximab ( INF ) , Etanercept ( ETN ) , and Adalimumab ( ADA ) in patients with psoriatic arthritis ( PsA ) with inadequate response to a previous disease-modifying antirheumatic drug ( DMARD ) . One hundred consecutive PsA patients with inadequate response to a previous DMARD entered this study . Clinical and laboratory assessment at baseline ( T0 ) and 12 ( T12 ) months were performed and included physical examination , vital signs , global Psoriasis Area and Severity Index ( PASI ; extension of psoriasis ) , tender joints count ( TJC ) , swollen joint count , health assessment question naire ( HAQ ; question naire for measuring disability ) , and monitoring of adverse events ( AEs ) . After enrolment , all patients were r and omly given INF 5 mg/Kg every 6–8 weeks , ETN 50 mg weekly , or ADA 40 mg every other week . Baseline therapy with DMARD remained unchanged . Effectiveness was defined as percentage of ACR20 responders and as clinical remission and /or minimal disease activity at 12 months treatment . INF , ETN , and ADA all effectively controlled signs and symptoms of PsA. All variables tested showed at T12 for each treatment a significant variation from the baseline value . In particular , patients on INF and ADA showed the greatest improvement in terms of PASI , while patients on ETN showed the greatest improvement on TJC and HAQ . ACR response rates were 72 % of patients on ETN , 70 % of those on ADA , and 75 % of those patients on INF . Occurrence of AEs was reported in 15 % of the cases . Only two AEs in patients on INF were considered drug related , pneumonitis and thrombocytopenia , respectively . All tumor necrosis factor-α blockers significantly controlled signs and symptoms of PsA. An increased knowledge of the different profiles of these agents may help in optimizing their use Background Patient reported outcomes ( PROs ) are especially useful in assessing treatments for rheumatoid arthritis ( RA ) since they measure dimensions of health-related quality of life that can not be captured using strictly objective physiological measures . The aim of this study was to compare the effects of combination etanercept and methotrexate ( ETN + MTX ) versus combination synthetic disease modifying antirheumatic drugs ( DMARDs ) and methotrexate ( DMARD + MTX ) on PRO measures among RA patients from the Asia-Pacific region , a population not widely studied to date . Patients with established moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate  were studied . Methods Patients were r and omized to either ETN + MTX ( N = 197 ) or DMARD + MTX ( N = 103 ) in an open-label , active-comparator , multicenter study , with PRO measures design ed as prospect i ve secondary endpoints . The Health Assessment Question naire ( HAQ ) , Functional Assessment of Chronic Illness Therapy Fatigue Scale ( FACIT-Fatigue ) , Medical Outcomes Short Form-36 Health Survey ( SF-36 ) , Hospital Anxiety and Depression Scale ( HADS ) and the Work Productivity and Activity Impairment Question naire : General Health ( WPAI : GH ) were used . Results Significantly greater improvements were noted for the ETN + MTX group at week16 for HAQ mean scores and for proportion of patients achieving HAQ score ≤ 0.5 , compared to patients in the DMARD + MTX group . SF-36 Summary Scores for physical and mental components and for 6 of 8 health domains showed significantly greater improvements at week16 for the ETN + MTX group ; only scores for physical functioning and role-emotional domains did not differ significantly between the two treatment arms . Greater improvements at week16 were noted for the ETN + MTX group for FACIT-Fatigue , HADS , and WPAI : GH mean scores . Conclusion Combination therapy using ETN + MTX demonstrated superior improvements using a comprehensive set of PRO measures , compared to combination therapy with usual st and ard of care DMARDs plus MTX  in patients with established rheumatoid arthritis from the Asia-Pacific region . Trial registration clintrials.gov # OBJECTIVES To evaluate long-term safety and efficacy of etanercept ( ETN ) in patients with rheumatoid arthritis ( RA ) without concomitant disease-modifying antirheumatic drug therapy . METHODS A total of 549 patients enrolled in this 5-year , open-label extension after completing 1 of 2 r and omised controlled studies ; all patients received ETN 25 mg twice weekly during the extension . Safety assessment s included physical exams , adverse events ( AEs ) , vital signs , laboratory tests , and autoantibody evaluations . Key efficacy endpoints included numbers of responders achieving the American College of Rheumatology ( ACR ) criteria , low disease activity scores , and disease remission . RESULTS Three hundred and eight ( 56 % ) patients completed the 5-year extension study . Total ETN exposure , including that received during the double-blind studies was 2212 patient-years . Withdrawals for efficacy- and safety-related reasons were 12 % and 19 % , respectively . The most common AE was upper respiratory infection ( 44 % ) . Rates of serious infections decreased over the 5-year period ; one case of suspected tuberculosis was reported . Rates of malignancies remained generally consistent during the 5-year period . There were no reports of demyelinating disease , serious blood dyscrasias , or opportunistic infections . The relationship between autoantibody titres and clinical events was not statistically significant . Less than 5 % of patients tested positive for anti-etanercept antibodies and all antibodies were non-neutralising . After 5 years , ACR 20 , 50 , and 70 response rates were 78 % , 51 % , and 32 % , respectively ; the mean percentage of patients achieving low disease activity score ( DAS ≤ 2.4 ) and remission ( DAS ≤ 1.6 ) were 44 % and 20 % , respectively . CONCLUSIONS ETN maintained a favourable safety profile and consistent efficacy throughout the 5-year study duration
This meta- analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS .
Compared with SSZ , ETN markedly decreased the BASDAI and CRP levels .
Etanercept ( ETN ) has been widely applied in the treatment of ankylosing spondylitis ( AS ) .
As the use of ETN has increased , associated adverse effects have been reported frequently .
Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo ( PBO ) .
The present meta- analysis evaluated r and omised controlled trials ( RCTs ) to compare the effects of ETN and a PBO or sulfasalazine ( SSZ ) in patients with AS .