title: Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis Efficacy of etanercept on rheumatic signs and pulmonary function tests in advanced ankylosing spondylitis: results of a randomised double-blind placebo-controlled study (SPINE) Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial The role of etanercept in ankylosing spondylitis. [A multicenter, double-blind, randomized, placebo-controlled clinical trial of etanercept treatment of Chinese patients with active ankylosing spondylitis]. Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Abnormal high-expression of CD154 on T lymphocytes of ankylosing spondylitis patients is down-regulated by etanercept treatment Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. Recombinant human tumor necrosis factor receptor (etanercept) for treating ankylosing spondylitis: a randomized, controlled trial. Six-month results of a double-blind, placebo-controlled trial of etanercept treatment in patients with active ankylosing spondylitis.
abstract: Objective : A double blind , r and omised , placebo controlled study to evaluate the safety and efficacy of etanercept to treat adult patients with ankylosing spondylitis ( AS ) . Methods : Adult patients with AS at 14 European sites were r and omly assigned to 25 mg injections of etanercept or placebo twice weekly for 12 weeks . The primary efficacy end point was an improvement of at least 20 % in patient reported symptoms , based on the multicomponent Assessment s in Ankylosing Spondylitis ( ASAS ) response criteria ( ASAS 20 ) . Secondary end points included ASAS 50 and ASAS 70 responses and improved scores on individual components of ASAS , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , acute phase reactants , and spinal mobility tests . Safety was evaluated during scheduled visits . Results : Of 84 patients enrolled , 45 received etanercept and 39 received placebo . Significantly more etanercept patients than placebo patients responded at the ASAS 20 level as early as week 2 , and sustained differences were evident up to week 12 . Significantly more etanercept patients reported ASAS 50 responses at all times and ASAS 70 responses at weeks 2 , 4 , and 8 ; reported lower composite and fatigue BASDAI scores ; had lower acute phase reactant levels ; and had improved spinal flexion .  Etanercept was well tolerated . Most adverse events were mild to moderate ; the only between-group difference was injection site reactions , which occurred significantly more often in etanercept patients . Conclusions : Etanercept is a well tolerated and effective treatment for reducing clinical symptoms and signs of AS Objectives 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 Etanercept , a tumour-necrosis-factor inhibitor , has shown efficacy in the treatment of rheumatoid arthritis . Psoriatic arthritis and psoriasis are disease states in which tumour necrosis factor , a proinflammatory cytokine , is present in increased concentrations in joints and in the skin . Therefore , psoriatic arthritis and psoriasis may be appropriate therapeutic targets for etanercept . METHODS This r and omised , double-blind , placebo-controlled , 12 week study assessed the efficacy and safety of etanercept ( 25 mg twice-weekly subcutaneous injections ) or placebo in 60 patients with psoriatic arthritis and psoriasis . Psoriatic arthritis endpoints included the proportion of patients who met the Psoriatic Arthritis Response Criteria ( PsARC ) and who met the American College of Rheumatology preliminary criteria for improvement ( ACR20 ) . Psoriasis endpoints included improvement in the psoriasis area and severity index ( PASI ) and improvement in prospect ively-identified individual target lesions . FINDINGS In this 12 week study , 26 ( 87 % ) of etanercept-treated patients met the PsARC , compared with seven ( 23 % ) of placebo-controlled patients . The ARC20 was achieved by 22 ( 73 % ) of etanercept-treated patients compared with four ( 13 % ) of placebo-treated patients . Of the 19 patients in each treatment group who could be assessed for psoriasis ( > or = 3 % body surface area ) , five ( 26 % ) of etanercept-treated patients achieved a 75 % improvement in the PASI , compared with none of the placebo-treated patients ( p=0.015 ) . The median PASI improvement was 46 % in etanercept-treated patients versus 9 % in placebo-treated patients ; similarly , median target lesion improvements were 50 % and 0 , respectively . Etanercept was well tolerated . INTERPRETATION Etanercept offers patients with psoriatic arthritis and psoriasis a new therapeutic option for control of their disease Ankylosing spondylitis is a chronic inflammatory disease that leads to significant loss of function and disability in patients . Current conventional therapies have not demonstrated improvement in axial symptoms and progressive ankylosis of the spine . The use of new biologic agents that block the actions of tumor necrosis factor-alpha have , for the first time , reported significant improvement in axial symptoms and reduction in spinal inflammation in short-term studies . Future studies with larger numbers of patients over long periods of time will eventually determine the long-term success and safety of these agents OBJECTIVE To evaluate the efficacy and safety of etanercept 50 mg once-weekly treatment of Chinese patients with active ankylosing spondylitis ( AS ) . METHODS Four hundred patients with active AS , enrolled in six medical centers , were r and omly divided into either the treatment group or the placebo group in a 3:1 ratio . The total length of the study was 12 weeks . The first 6-week period was a double-blind placebo controlled treatment period and the second 6-week period was an open-labeled treatment period . During the first 6-week period , 300 patients in the treatment group received once-weekly subcutaneous injection of etanercept ( 50 mg ) , whereas the 100 patients in the placebo group received placebo injection . During the second 6-week period , patients in both groups received etanercept ( 50 mg once weekly subcutaneous injection ) . The primary end point was the percentage of patients achieving the Assessment s in Ankylosing Spondylitis ( ASAS ) 20 % response ( ASAS 20 ) at week 6 . Other outcome measures included the percentage of patients achieving ASAS 5/6 , partial remission and Bath AS disease activity index 50 ( BASDAI 50 ) responses at week 12 . RESULTS A total of 381 patients completed the trial , including 285 patients in the etanercept group and 96 patients in the placebo group . At week 2 , the percentage of patients achieving ASAS 20 in the etanercept group was 55.7 % , whereas the placebo group was only 17.0 % ( P < 0.001 ) . At week 6 , 77.5 % of patients in the etanercept group achieved ASAS 20 as compared with 32.3 % in the placebo group ( P < 0.001 ) . At the end of 12 weeks , the percentage of patients in the etanercept group achieving the ASAS 20 was 89.5 % . Improvements of other measures were also significant in the etanercept group . Etanercept was well tolerated and no malignancy and life-threatening events were observed in this study . Most adverse events observed were mild injection-site reactions . CONCLUSION Etanercept 50 mg weekly treatment of Chinese patients with active ankylosing spondylitis is convenient , fast-acting , highly effective , and well tolerated OBJECTIVE Etanercept , a fully human tumor necrosis factor ( TNF ) receptor , is an effective treatment in patients with ankylosing spondylitis ( AS ) .  Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS , and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present . Until now , no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine . This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS . METHODS In this r and omized , double-blind study , patients received etanercept 50 mg once weekly ( n=379 ) or sulfasalazine titrated to a maximum of 3 gm/day ( n=187 ) for 16 weeks . The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20 % improvement ( ASAS20 ) at 16 weeks . Last observation carried forward was predefined for imputation of missing values . RESULTS The mean age of the patients was 41 years , 74 % were male , and the mean disease duration was 7.6 years . The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine ( 75.9 % versus 52.9 % ; P<0.0001 ) . As early as week 2 of treatment , etanercept was found to be more effective than sulfasalazine ( P<0.0001 ) in ameliorating both the axial symptoms and peripheral manifestations . Serious adverse events rarely occurred , and the rate of serious adverse events did not differ between groups . CONCLUSION In this population of patients with AS , etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints The pathogenesis of ankylosing spondylitis ( AS ) still remains an enigma . Although some studies have indicated the importance of T-cells and proinflammatory cytokines in the pathogenesis of the AS , it is still unknown whether co-stimulatory molecule CD154 participates in the pathogenesis of AS and how its level changes during the anti-TNF-α treatment of AS . This study is performed to evaluate the expression of CD154 in peripheral blood T-lymphocytes of patients with AS and observe the change of CD154 in etanercept-treated AS patient . We collected the peripheral blood and clinical data from 66 AS , 30 rheumatoid arthritis ( RA ) patients , and 30 healthy controls . Thirty-nine active AS patients were enrolled in a r and omized double-blind placebo-controlled trial . We followed up 37 cases that fulfilled the ASAS20 response criteria after they finished etanercept treatment till week 48 . The percentage of CD3+CD154 + in peripheral blood lymphocytes was evaluated by flow cytometry . We found that CD154 expression in AS patients was significantly higher than that in healthy volunteers and RA patients ( both P < 0.001 ) . The expressions of CD154 in AS patients at active stage or with peripheral joint involvement were significantly higher than those at stable stage or with axial involvement alone ( P = 0.005 and 0.044 , respectively ) . The expression of CD154 decreased in AS patients treated with etanercept compared with patients treated with placebo at week 6 ( P < 0.001 ) . Compared with healthy volunteers , the expression of CD154 in 16 AS patients who relapsed after finishing etanercept treatment was elevated again ( P = 0.012 ) . These findings show that co-stimulatory molecule CD154 is overexpressed on T-lymphocytes in peripheral blood of AS patients and can be down-regulated by etanercept treatment , which suggest that CD154 might be involved in the inflammatory evolvement of AS and might be a potential biomarker to monitor AS disease activity and the effect of etanercept treatment OBJECTIVE To develop criteria for symptomatic improvement in patients with ankylosing spondylitis ( AS ) , using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs ( NSAIDs ) . METHODS Patient data from 5 short-term , r and omized , controlled trials were used to assess equivalence , reliability , and responsiveness of multiple items in the 5 outcome domains for AS treatment : physical function , pain , spinal mobility , patient global assessment , and inflammation . At least one measure per domain was responsive ( st and ardized response mean of > 0.5 ) , except for the spinal mobility domain , which was omitted from the criteria . We developed and tested c and i date improvement criteria in a r and om two-thirds subset from the 3 largest trials and used the remaining one-third for validation . These 3 largest trials included 923 patients ( 631 receiving NSAIDs , 292 in placebo groups ) . We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of < or = 25 % . RESULTS C and i date definitions were changes in single domains and in multiple measure indices , as well as combinations of improvements in multiple domains . Worsening in a domain was defined as a change for the worse of > or = 20 % and a net change for the worse of > or = 10 units on a scale of 0 - 100 . Partial remission ( for comparison purpose s ) was defined as an end-of-trial value of < 20/100 in each of the 4 domains . Among 20 c and i date criteria , change of > or = 20 % and > or = 10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset ( 51 % of patients improved with NSAIDs , 25 % with placebo ; chi2 = 36.4 , P < 0.001 ) . Results were confirmed in the validation subset . Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion . Among all 923 patients , improvement rates using this criterion were 49 % for NSAID-treated patients and 24 % for placebo-treated patients . CONCLUSION Although further validation using data from new trials is still needed , we conclude that we have developed a clinical ly valid , easy-to-use measure of short-term improvement in AS OBJECTIVE To determine the safety and efficacy of etanercept in a multicenter , r and omized , placebo-controlled , double-blind trial of adults with moderate to severe active ankylosing spondylitis ( AS ) . METHODS Patients ( n = 277 ) were treated with either etanercept 25 mg ( n = 138 ) or placebo ( n = 139 ) subcutaneously twice weekly for 24 weeks . The primary outcome measures were the percentages of patients achieving the Assessment s in Ankylosing Spondylitis 20 % response ( ASAS20 ) at weeks 12 and 24 . Other outcome measures included the percentage of patients achieving higher ASAS responses , and the safety of etanercept in patients with AS . All outcome measures were assessed at 2 , 4 , 8 , 12 , and 24 weeks . RESULTS Treatment with etanercept result ed in dramatic improvement . The ASAS20 was achieved by 59 % of patients in the etanercept group and by 28 % of patients in the placebo group ( P < 0.0001 ) at week 12 , and by 57 % and 22 % of patients , respectively , at week 24 ( P < 0.0001 ) . All individual ASAS components , acute-phase reactant levels , and spinal mobility measures were also significantly improved . The safety profile of etanercept was similar to that reported in studies of patients with rheumatoid arthritis or psoriatic arthritis . The only adverse events that occurred significantly more often in the etanercept group were injection-site reactions , accidental injuries , and upper respiratory tract infections . CONCLUSION Etanercept is a highly effective and well tolerated treatment in patients with active AS OBJECTIVE There is increasing evidence that tumor necrosis factor alpha ( TNFalpha ) is central ly involved in the pathogenesis of ankylosing spondylitis ( AS ) and other spondylarthritides . This study was design ed to investigate the efficacy of anti-TNFalpha therapy with etanercept , a 75-kd receptor fusion protein , in active AS . METHODS This multicenter trial had 2 phases : an initial placebo-controlled period of 6 weeks ' duration and an observational phase lasting 24 weeks . Thirty patients with active AS were included . They were r and omized into 2 groups , which received either etanercept ( 25 mg twice weekly ) ( n = 14 ) or placebo ( n = 16 ) for 6 weeks . Then both groups were treated with etanercept . Nonsteroidal antiinflammatory drug ( NSAID ) treatment could be continued , but disease-modifying antirheumatic drugs ( DMARDs ) and steroids had to be withdrawn prior to the study . All patients received etanercept for a total of 12 weeks and were followed up for at least 24 weeks . The Bath AS Disease Activity Index ( BASDAI ) , Bath AS Functional Index , Bath AS Metrology Index , pain level on a numeric rating scale , quality of life by the Short Form 36 , and C-reactive protein ( CRP ) level were assessed . The primary outcome parameter was a > or=50 % improvement in the BASDAI . RESULTS Treatment with etanercept result ed in at least a 50 % regression of disease activity in 57 % of these patients at week 6 , versus 6 % of the placebo-treated patients ( P = 0.004 ) . After the placebo-treated patients switched to etanercept , 56 % improved . The mean + /- SD BASDAI improved from 6.5 + /- 1.2 at baseline to 3.5 + /- 1.9 at week 6 in the etanercept group , with no improvement in the placebo group ( P = 0.003 between groups ) . Similarly , pain , function , mobility , and quality of life improved with etanercept but not with placebo at week 6 ( P < 0.05 ) . Mean CRP levels decreased significantly with etanercept but not with placebo ( P = 0.001 ) . There was ongoing improvement in all parameters in both groups until week 12 and week 18 , respectively ( i.e. , throughout the period of etanercept treatment ) . Disease relapses occurred a mean + /- SD of 6.2 + /- 3.0 weeks after cessation of etanercept . No severe adverse events , including major infections , were observed during the trial . CONCLUSION This study shows that on a short-term basis ( 3 months ) , treatment with etanercept is clearly efficacious in patients with active AS who are receiving NSAID therapy but not DMARDs or steroids .  After cessation of therapy , almost all patients experienced a relapse within a few weeks . Thus , it seems probable that etanercept must be administered continuously in most AS patients to achieve permanent inhibition of the inflammatory process
target: 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 .
background: 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 .