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and methotrexate to induce remission in early inflammatory arthritis: the EMPIRE trial The Effect of Reduced or Withdrawn Etanercept-methotrexate Therapy on Patient-reported Outcomes in Patients with Early Rheumatoid Arthritis Rapid and sustained improvement in health-related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.
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
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 .