Frequency and characteristics of disease flares in ankylosing spondylitis Predictors of response to anti-TNF therapy in ankylosing spondylitis: results from the British Society for Rheumatology Biologics Register Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1 Outcomes of a multicentre randomised clinical trial of etanercept to treat ankylosing spondylitis A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study The effects of golimumab on subclinical atherosclerosis and arterial stiffness in ankylosing spondylitis—a randomized, placebo-controlled pilot trial. 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The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection Evaluation of the nonsteroidal anti-inflammatory drug-sparing effect of etanercept in axial spondyloarthritis: results of the multicenter, randomized, double-blind, placebo-controlled SPARSE study The effect of two golimumab doses on radiographic progression in ankylosing spondylitis: results through 4 years of the GO-RAISE trial Effectiveness of switching between TNF inhibitors in ankylosing spondylitis: data from the NOR-DMARD register [A multicenter, double-blind, placebo-controlled, randomized, phase III clinical study of etanercept in treatment of ankylosing spondylitis]. Efficacy and safety of up to 192 weeks of etanercept therapy in patients with ankylosing spondylitis. Golimumab administered subcutaneously every 4 weeks in ankylosing spondylitis: 5-year results of the GO-RAISE study Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study Variations in population health status: results from a United Kingdom national questionnaire survey Efficacy and safety of infliximab in patients with ankylosing spondylitis over a two-year period. A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis The impact of tumor necrosis factor α inhibitors on radiographic progression in ankylosing spondylitis. 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Objective . To examine the characteristics and frequency of disease flares in a cohort of people with AS . Methods . A prospect i ve data set from a r and omized controlled trial ( RCT ) of a probiotic treatment/placebo was utilized to examine disease flares in 134 people with AS . Disease flares were defined as either minor/localized flares ( pain/swelling localized to one area with fatigue and stiffness ) or major/generalized flares ( generalized pain , hot burning joints , muscle spasm , fever , sweating , extreme fatigue and stiffness ) . Results . One hundred and thirty-four people were followed up for 1216 person follow-up weeks and there were 71.4 flares per 100 person-weeks . Of these , 12 were major/generalized flares and 59.4 were minor/localized flares . People who experienced at least one major/generalized flare during the study period had worse disease during flare-free periods in terms of disease activity , impaired function , self-reported night pain and iritis compared with those who did not experience any major/generalized flares during the study . Major/generalized flares lasted for an average of 2.4 weeks ( s.d . 2.7 ) , and were preceded by and followed by a minor/localized flare in 92 % ( 55/60 ) of cases . Conclusion . Seventy per cent of people with AS felt they had a flare in any given week . Those who experienced major/generalized flares appear to have more severe and active disease even during periods when not in flare , compared with those who do not experience major/generalized flares . These results have implication s for the timing of assessment s prior to starting anti-TNF therapy and suggest that the presence of major flares may be helpful in identifying patients with severe disease Objective . Few data exist on the use of anti-TNF drugs for AS during routine clinical use in the UK . This report describes an improvement in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) and Bath Ankylosing Spondylitis Functional Index ( BASFI ) after 6 months of therapy in 261 patients enrolled in a national prospect i ve observational register . Methods . The British Society for Rheumatology Biologics Register ( BSRBR ) recruited patients starting anti-TNF therapy for AS between 2002 and 2006 . Multivariable linear regression models were used to estimate the predictors of absolute improvement in BASDAI and BASFI at 6 months . Covariates included age , gender , disease duration , baseline BASDAI and BASFI , presence of raised inflammatory markers ( defined as twice the upper limit of normal ) and DMARD therapy . Results . The cohort was young ( median age 43 years ) and 82 % were males .  Median baseline BASDAI was 7.6 and BASFI 7.9 . At 6 months , the mean improvements in BASDAI and BASFI were 3.6 and 2.6 U , respectively ; 52 % reached a BASDAI50 . Patients with raised inflammatory markers at the start of therapy had a 0.9-U ( 95 % CI 0.2 , 1.5 ) better improvement in BASDAI compared with those without . Lesser responses were seen in those with higher baseline BASFI scores . Women had a 1.1-U ( 95 % CI 0.3 , 2.0 ) greater improvement in BASFI at 6 months , as did those who were receiving concurrent DMARD therapy [ 0.9 U ( 95 % CI 0.2 , 1.7 ) ] . Conclusions . The majority of patients receiving anti-TNF therapy for AS during routine care demonstrated an improvement in disease activity . Raised inflammatory markers at the start of therapy predicted a greater improvement in BASDAI , identifying a group of patients who may be more responsive to anti-TNF therapies , although the results were not confined to this group Objectives To assess whether combination therapy with infliximab ( IFX ) plus nonsteroidal anti-inflammatory drugs ( NSAIDs ) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society ( ASAS ) partial remission in patients with early , active axial spondyloarthritis ( SpA ) who were naïve to NSAIDs or received a submaximal dose of NSAIDs . Methods Patients were r and omised ( 2 : 1 ratio ) to receive naproxen ( NPX ) 1000 mg daily plus either IFX 5 mg/kg or placebo ( PBO ) at weeks 0 , 2 , 6 , 12 , 18 and 24 . The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28 . Several other measures of disease activity , clinical symptoms and patient-rated outcomes were evaluated . Treatment group differences were analysed with Fisher exact tests or analysis of covariance . Results A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group ( 61.9 % ; 65/105 ) than in the PBO+NPX group ( 35.3 % ; 18/51 ) at week 28 ( p=0.002 ) and at all other visits ( p<0.05 , all comparisons ) . Results of most other disease activity and patient-reported endpoints ( including Ankylosing Spondylitis Disease Activity Score , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , multiple quality of life measures and pain measures ) showed greater improvement in the IFX+NPX group than the PBO+NPX group , with several measures demonstrating early and consistent improvement over 28 weeks of treatment . Conclusions Patients with early , active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone . NPX alone led to clinical remission in a third of patients 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 To compare the pharmacokinetics ( PK ) , safety and efficacy of innovator infliximab ( INX ) and CT-P13 , a biosimilar to INX , in patients with active ankylosing spondylitis ( AS ) . Methods Phase 1 r and omised , double-blind , multicentre , multinational , parallel-group study . Patients were r and omised to receive 5 mg/kg of CT-P13 ( n=125 ) or INX ( n=125 ) . Primary endpoints were area under the concentration-time curve ( AUC ) at steady state and observed maximum steady state serum concentration ( Cmax , ss ) between weeks 22 and 30 . Additional PK , efficacy endpoints , including 20 % and 40 % improvement response according to Assessment in Ankylosing Spondylitis International Working Group criteria ( ASAS20 and ASAS40 ) , and safety outcomes were also assessed . Results Geometric mean AUC was 32 765.8 μgh/ml for CT-P13 and 31 359.3 μgh/ml for INX . Geometric mean Cmax , ss was 147.0 μg/ml for CT-P13 and 144.8 μg/ml for INX . The ratio of geometric means was 104.5 % ( 90 % CI 94 % to 116 % ) for AUC and 101.5 % ( 90 % CI 95 % to 109 % ) for Cmax , ss . ASAS20 and ASAS40 responses at week 30 were 70.5 % and 51.8 % for CT-P13 and 72.4 % and 47.4 % for INX , respectively . In the CT-P13 and INX groups more than one adverse event occurred in 64.8 % and 63.9 % of patients , infusion reactions occurred in 3.9 % and 4.9 % , active tuberculosis occurred in 1.6 % and 0.8 % , and 27.4 % and 22.5 % of patients tested positive for anti-drug antibodies , respectively . Conclusions The PK profiles of CT-P13 and INX were equivalent in patients with active AS . CT-P13 was well tolerated , with an efficacy and safety profile comparable to that of INX up to week 30 OBJECTIVE Our aim was to ascertain the efficacy of golimumab compared with placebo in the prevention of atherosclerosis and arterial stiffness in AS . METHODS A r and omized , double-blind , placebo-controlled pilot study was performed in which AS patients were treated with  golimumab ( n = 20 ) and placebo  ( n = 21 ) for 12 months . Patients from the placebo group who failed to achieve a 20 % response to Assessment of SpondyloArthritis international Society criteria ( ASAS20 ) at 6 months received open-label golimumab .  Intima-media thickness ( IMT ) , pulse wave velocity ( PWV ) and augmentation index ( AIx ) were measured at baseline , 6 and 12 months . RESULTS At 6 months , 11/20 ( 55 % ) and 3/21 ( 14 % ) patients from the golimumab and placebo groups achieved an ASAS20 response , respectively ( P = 0.006 ) . There was no significant difference in the change of the vascular parameters between the two groups . In the placebo group , significantly greater progression of the mean IMT [ from 0.51 mm ( S.D. 0.07 ) at baseline to 0.53 mm ( S.D. 0.08 ) at 6 months , P = 0.044 ] and PWV ( from 12.2 m/s ( S.D. 1.6 ) at baseline to 12.6 m/s ( S.D. 1.3 ) , P = 0.028 ] were observed . There was a trend towards progression of the mean IMT in the golimumab group ( P = 0.099 ) but the maximum IMT , PWV and AIx remained unchanged . At 12 months the changes in vascular parameters were similar between the early and delayed ( or no ) golimumab groups . CONCLUSION Uncontrolled inflammation may result in a significant progression in IMT and PWV in patients with AS . Arterial dysfunction may be prevented by golimumab over a period of 6 months , probably because of effective suppression of inflammation . TRIAL REGISTRATION clinical trials.gov ( NCT01212653 Purpose To evaluate the efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis ( nr-axSpA ) . Methods Patients fulfilled Assessment of Spondyloarthritis international Society ( ASAS ) criteria for axial spondyloarthritis , had a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score of ≥ 4 , total back pain score of ≥ 4 ( 10 cm visual analogue scale ) and inadequate response , intolerance or contraindication to non-steroidal anti-inflammatory drugs ( NSAIDs ) ; patients fulfilling modified New York criteria for ankylosing spondylitis were excluded . Patients were r and omised to adalimumab ( N=91 ) or placebo ( N=94 ) . The primary endpoint was the percentage of patients achieving ASAS40 at week 12 . Efficacy assessment s included BASDAI and Ankylosing Spondylitis Disease Activity Score ( ASDAS ) . MRI was performed at baseline and week 12 and scored using the Spondyloarthritis Research Consortium of Canada ( SPARCC ) index . Results Significantly more patients in the adalimumab group achieved ASAS40 at week 12 compared with patients in the placebo group ( 36 % vs 15 % , p<0.001 ) . Significant clinical improvements based on other ASAS responses , ASDAS and BASDAI were also detected at week 12 with adalimumab treatment , as were improvements in quality of life measures . Inflammation in the spine and sacroiliac joints on MRI significantly decreased after 12 weeks of adalimumab treatment . Shorter disease duration , younger age , elevated baseline C-reactive protein or higher SPARCC MRI sacroiliac joint scores were associated with better week 12 responses to adalimumab . The safety profile was consistent with what is known for adalimumab in ankylosing spondylitis and other diseases . Conclusions In patients with nr-axSpA  , adalimumab treatment result ed in effective control of disease activity , decreased inflammation and improved quality of life  compared with placebo . Results from ABILITY-1 suggest that adalimumab has a positive benefit – risk profile in active nr-axSpA patients with inadequate response to NSAIDs OBJECTIVE To compare the abilities of three enthesitis indices to detect improvement in entheseal tenderness with the TNF antagonist golimumab in AS . METHODS Adult patients with active AS were r and omly assigned to receive s.c . injections of placebo or golimumab ( 50 or 100 mg ) every 4 weeks . Patients with inadequate week 16 responses were switched ( blinded ) from placebo to golimumab 50 mg or from golimumab 50 mg to 100 mg . At week 24 , all patients still receiving placebo crossed over to golimumab 50 mg . Enthesitis data through week 52 are reported herein . Enthesitis was measured by a trained , independent assessor who recorded the presence or absence of tenderness in 27 entheses , which allowed simultaneous determination of three different indices [ 12-point Berlin Index , 17-point University of California , San Francisco ( UCSF ) Index and 13-point Maastricht AS Enthesitis Score ( MASES ) ] . RESULTS Three hundred and fifty-six AS patients were r and omized to placebo ( n = 78 ) , golimumab 50 mg ( n = 138 ) or golimumab 100 mg ( n = 140 ) ; 355 had enthesitis data available for analysis . Using the UCSF Index , significant improvement from baseline vs placebo was observed for golimumab 100 mg at weeks 14 and 24 . Using the MASES , significant improvement for golimumab 100 mg vs placebo at week 14 and a trend toward improvement at week 24 were observed . Using the Berlin Index , significant improvement for golimumab 100 mg vs placebo at week 14 was observed . Effect size determinations for changes to weeks 14 , 24 and 52 , respectively , in the Berlin ( -0.27 , -0.34 , -0.42 ) , UCSF ( -0.44 , -0.61 , -0.55 ) and MASES ( -0.30 , -0.55 , -0.39 ) indices suggested small to moderate effect sizes . CONCLUSION In patients with active AS , the UCSF Index appeared most sensitive in detecting the effect of golimumab 100 mg vs placebo on enthesitis . TRIAL REGISTRATION clinical trials.gov , http://www . clinical trials.gov , NCT00265083 BACKGROUND There is insufficient evidence for the long-term efficacy and safety of anti-tumour necrosis factor therapy in patients with ankylosing spondylitis ( AS ) . This is the first report on the treatment with infliximab over 5 years . METHODS As part of a multicentre r and omised trial , 69 patients with active AS at baseline ( BL ) have been continuously treated with infliximab ( 5 mg/kg i.v . every 6 weeks)--except for a short discontinuation after 3 years ( FU1 ) . The primary outcome of this extension was remission according to the ASsessment in Ankylosing Spondylitis ( ASAS ) criteria at the end of year 5 of the study ( FU2 ) . RESULTS Of the 43 patients who completed year 3 , 42 agreed to continue , 38 of which ( 90.5 % ) finished year 5 ( 55 % of 69 initially ) . Partial clinical remission was achieved in 13 of 38 patients ( 34.2 % ) at FU1 and FU2 . At FU2 , the mean Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) was 2.5+/-1.9 ( BL:6.4 , FU1:2.5 ) . BASDAI values < 4 were seen in 79 % of patients at both , FU1 and FU2 . ASAS 20 % and 40 % responses were seen in 32 ( 84 % ) and 24 ( 63 % ) patients at FU2 , respectively . Most patients classified as non-responders at FU2 were part-time responders , as all but one patient achieved an ASAS 20 % response at least once within the last 2 years . Three types of responders were identified . No major side effects occurred during years 4 and 5 of infliximab therapy . CONCLUSIONS Infliximab is safe and efficacious in AS patients over 5 years . The majority of the patients remained on treatment and had rather persistent levels of low disease activity . Different response types could be identified 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 Objective : To evaluate the continued safety and durability of clinical response in patients with ankylosing spondylitis receiving etanercept .  Methods : 277 patients who had participated in a previous r and omised , double blind , placebo controlled 24 week trial were eligible to continue in this open label extension study . All patients who enrolled in the open label extension ( n = 257 ) received subcutaneous etanercept 25 mg twice weekly for up to 72 weeks , for a combined 96 weeks of cumulative trial and open label experience . For the patients who had received etanercept for 24 weeks in the double blind trial , this represented almost 2 years of continuous etanercept treatment . Results : Patients continuing etanercept treatment had a sustained response for almost 2 years , with 74 % achieving an ASsessment s in Ankylosing Spondylitis 20 % ( ASAS 20 ) response after 96 weeks of etanercept treatment . Patients who had received placebo in the preceding double blind trial had similar responses , with 70 % of patients attaining an ASAS 20 response after 24 weeks of etanercept treatment and 78 % achieving an ASAS 20 response after 72 weeks . Improved spinal mobility was seen in both groups . Etanercept was well tolerated in patients treated for up to 96 weeks . Conclusion : The subcutaneous administration of twice weekly doses of etanercept provided sustained durability of response in the improvement of signs and symptoms of ankylosing spondylitis for nearly 2 years Objective . To evaluate the 2-year efficacy and safety of etanercept in patients with ankylosing spondylitis ( AS ) . Methods . A 96-week open-label extension study , which followed a 12-week double-blind placebo-controlled trial , was design ed to provide longterm efficacy and safety data , including radiographic outcomes , for patients treated with etanercept 25 mg twice weekly ( NCT00421980 ) . In all , 81 patients were enrolled ( 96 % of the participants from the double-blind study ) . Key efficacy measures included improvement using the Assessment in Ankylosing Spondylitis 20 % ( ASAS20 ) criteria , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , and the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) . Radiographic progression was evaluated using the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) method . Paired t tests were used to test within-group changes from baseline . Results . The percentage of responders , by ASAS20 criteria , remained relatively constant in patients who received etanercept during the 12-week double-blind study ( 60 % at Week 0 and 83 % at Week 96 of the open-label extension ) ; more patients from the placebo group became responders after being switched to etanercept ( 23 % and 74 % , respectively ) . A similar trend was also observed using the ASAS40 and ASAS5/6 criteria , the BASFI , and the BASDAI . Most patients had no change from baseline in mSASSS values .  Etanercept was well tolerated ; the most frequent adverse events were injection site reactions ( n = 30 ; 37.0 % ) and headache ( n = 18 ; 22.2 % ) , and the most frequent infections were upper respiratory tract infections ( n = 43 ; 53.1 % ) and flu syndrome ( n = 22 ; 27.2 % ) . Conclusion . For 2 years , etanercept was clinical ly effective and well tolerated , with no unexpected safety findings OBJECTIVES To compare the impact of ankylosing spondylitis ( AS ) on health-related quality of life ( HRQL ) and of adalimumab on initial and sustained improvement in HRQL for patients with active AS versus the general US population . METHODS Data from the 5-year ATLAS trial were analysed . HRQL burden of AS and treatment impact on HRQL were assessed by comparing health status and utility scores from ATLAS ( Short Form 36 Health Survey [ SF-36 ] and Health Utilities Index Mark 3 [ HUI3 ] ) with population norms . RESULTS Baseline scores for all measures were comparable between adalimumab and placebo . All scores for both groups were significantly worse than general population norms ( all p<0.0001 ) . Within- and between-group improvements in SF-36 Physical Component Summary and SF-6D scores from baseline to Weeks 12 and 24 were clinical ly relevant for patients receiving adalimumab . For patients initially r and omised to adalimumab , HRQL scores improved from Weeks 25 to 52 and remained relatively stable through 3 years but remained lower than for the general US population at all time points . CONCLUSIONS Findings demonstrate a significant burden of AS on HRQL . Treatment with adalimumab significantly improved physical functioning and other measures of HRQL compared with placebo . Clinical ly relevant improvements in HRQL outcomes over 3 years represent a significant benefit of adalimumab . Because of the advanced AS disease , patient health status remained below that of the general population . Treatment earlier in the course of AS may be needed to restore HRQL to the level of the general population OBJECTIVES To assess long-term safety and clinical efficacy of etanercept 25 mg subcutaneously twice weekly up to 5 years in subjects with ankylosing spondylitis ( AS ) . METHODS An open-label ( OL ) , multicentre , phase 4 , 156-week extension study of subjects with AS who had completed a 12-week r and omised , placebo-controlled study ( N=84 ; n=45 etanercept , n=39 placebo ) followed by a 96-week OL study ( n=81 ; n=42 etanercept/etanercept ; n=39 placebo/etanercept ) ; 59 subjects who completed the 96-week OL extension enrolled in the current OL trial and continued etanercept 25 mg BIW for an additional 156 weeks ( total duration : 264 weeks , original etanercept group ; 252 weeks , original placebo group ) . Safety was based on spontaneous reports of adverse events ( AEs ) . Last observation carried forward was used for imputation of missing values . RESULTS Thirty-seven of 59 subjects ( 63 % ) completed 5 years of etanercept treatment . Serious non infectious AEs and serious infections occurred at a rate of 0.17 and 0.03 events per subject years , respectively ; inflammatory bowel disease and uveitis ( including iritis and iridiocyclitis ) occurred at 0.01 and 0.14 , respectively . No cases of tuberculosis or opportunistic infections were reported . Assessment in Ankylosing Spondylitis ( ASAS ) responses and improvements in Bath Ankylosing Spondylitis Functional Index and spinal mobility were sustained from week 108 through week 264 . CONCLUSIONS Etanercept was well tolerated with no new safety signals detected in subjects with AS over 5 years . Clinical efficacy and improvements in function and mobility seen during the double-blind and first OL study were sustained . These results support etanercept therapy for the long-term management of this chronic disease Objective : To determine the long-term effect of adalimumab on patients with ankylosing spondylitis ( AS ) who participated in the Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS ( ATLAS ) , a r and omised , double-blind , placebo controlled , 24-week trial . Methods : Patients received adalimumab 40 mg every other week ( eow ) or placebo for 24 weeks in ATLAS . At week 24 , patients were switched to open-label adalimumab 40 mg eow . Efficacy measures included 20 % improvement in the Assessment in SpondyloArthritis International Society ( ASAS ) criteria ( ASAS20 ) , ASAS40 and ASAS partial remission responses and changes in individual components of the ASAS20 response evaluations , for example , Bath AS Functional Index ( BASFI ) and Bath AS Disease Activity Index ( BASDAI ) . Two-year interim data were analysed based on the total duration of adalimumab exposure , irrespective of the treatment r and omisation group . Results : At 2 years , 255 ( 82.0 % ) of the original 311 ATLAS patients continued receiving adalimumab treatment . Improvements in ASAS responses observed in ATLAS were sustained during long-term treatment ; 64.5 % ( 200/310 ) were ASAS20 responders , 50.6 % ( 157/310 ) were ASAS40 responders and 33.5 % ( 104/310 ) had maintained ASAS-defined partial remission . Changes in individual ASAS response components were sustained or improved during long-term adalimumab treatment . From ATLAS baseline to 2 years of adalimumab exposure , respectively , BASDAI improved from 6.3 ( SD 1.7 ) to 2.4 ( SD 2.3 ) and BASFI improved from 5.2 ( SD 2.4 ) to 2.9 ( SD 2.5 ) . Adalimumab was well tolerated . No cases of tuberculosis , congestive heart failure , lupus-like symptoms , or demyelinating disease were reported . Conclusions : Adalimumab reduced the signs and symptoms of AS and induced partial remission for up to 2 years . The long-term safety profile was similar to the short-term safety profile . Trial registration information : Objective . The tumor necrosis factor-α ( TNF-α ) inhibitor infliximab ( IFX ) has been proven effective for the treatment of ankylosing spondylitis ( AS ) . The primary objective of this double-blind , placebo-controlled study was to assess the safety and efficacy of low-dose ( 3 mg/kg q8w ) IFX therapy in AS . Methods . In the 12-week double-blind phase of the study , patients ( N = 76 ) were r and omized to infusions of placebo or IFX ( 3 mg/kg ) at Weeks 0 , 2 , and 6 . The primary endpoint was 20 % improvement in ASsessment s in Ankylosing Spondylitis criteria ( ASAS20 ) at 12 weeks . In the open-label extension phase , all patients received scheduled IFX infusions ( q 8 weeks ) up to 46 weeks . Patients who did not meet target response criteria ( i.e. ,  BASDAI score did not improve by at least 50 % and was > 3 ) at Weeks 22 or 38 had a dose increase to IFX 5 mg/kg . Results . At 12 weeks , 53.8 % of IFX-treated patients achieved ASAS20 , compared with 30.6 % of placebo-treated patients ( p = 0.042 ) . IFX-treated patients showed significant improvement in measures of disease activity , spinal mobility , and quality of life over the course of the study . During the extension phase , 68 % of patients in the IFX group did not meet the clinical target and had an increase in the dose of IFX to 5 mg/kg by 38 weeks . In general , IFX was safe and well tolerated  . Ten patients withdrew from the study for various reasons , with only 2 ( 2.6 % ) attributed to adverse events . Conclusion . IFX 3 mg/kg was effective in reducing the signs and symptoms of active AS , and was generally safe and well tolerated . Dose escalation to 5 mg/kg every 8 weeks was warranted in most patients to achieve the target clinical response of the study Introduction We evaluated the three-year impact of adalimumab on  patient-reported physical function and health-related quality -of-life ( HRQOL ) outcomes  in patients with active ankylosing spondylitis ( AS ) . Methods The Adalimumab Trial Evaluating Long-Term Efficacy and Safety in AS ( ATLAS ) is an ongoing five-year study that included an initial 24-week , r and omized , placebo-controlled , double-blind period , followed by open-label extension treatment with adalimumab .  Clinical and HRQOL data collected for up to three years from ATLAS were used for these analyses . Patients were r and omized to receive adalimumab 40 mg or placebo  by subcutaneous injection every other week . Physical function was assessed by the Bath AS Functional Index ( BASFI ) , as well as by the Short Form 36 ( SF-36 ) Health Survey Physical Component Summary ( PCS ) and Physical Function subscale scores . HRQOL was assessed using the AS Quality of Life ( ASQOL ) question naire . Disease activity was assessed by the Bath AS Disease Activity Index ( BASDAI ) . Results Of 315 patients enrolled in ATLAS , 288 ( 91 % ) participated in an open-label adalimumab treatment extension and 82 % provided three-year outcome data . During the 24-week double-blind phase , adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the BASDAI ( P < 0.001 ) , BASFI ( P < 0.001 ) , ASQOL ( P < 0.001 ) , and both the SF-36 PCS ( P < 0.001 ) and Physical Function subscale ( P < 0.001 ) scores , but not the SF-36 Mental Component Summary score ( P = 0.181 ) and Mental Health subscale scores ( P = 0.551 ) . Mean changes from baseline through three years of adalimumab treatment were statistically significant for the BASDAI ( change score : -3.9 , P < 0.001 ) , BASFI ( change score : -29.6 , P < 0.001 ) , SF-36 PCS ( change score : 11.6 , P < 0.001 ) , and Physical Function ( change score : 23.3 , P < 0.001 ) . Comparable results were observed for the other SF-36 scores and for the ASQOL ( all P < 0.001 ) . Conclusions Adalimumab significantly improved disease activity , patient-reported physical function , and HRQOL . These benefits were maintained over three years of treatment in patients with AS.Trial registration Clinical Trials.gov NCT00085644 Objective : To examine the efficacy and safety of infliximab combined with methotrexate compared with methotrexate alone in the treatment of ankylosing spondylitis ( AS ) using MRI and DXA to monitor its impact on bone . Methods : In this single centre study 42 subjects with active AS were treated with methotrexate and were r and omly assigned , in a ratio of 2:1 , to receive five infusions of either 5 mg/kg infliximab or placebo over 30 weeks . The primary outcome was improvement in disease activity as shown by the BASDAI at week 30 . MRI was used to assess the effect of treatments on sacroiliac and spinal enthesitis/osteitis and DXA to monitor bone mineral density . Results : Both therapeutic agents were well tolerated with no dropouts due to adverse events . A significantly greater improvement in mean BASDAI score was seen in the infliximab arm at week 10 ( p = 0.017 ) than in the placebo arm , but this was not maintained by week 30 ( p = 0.195 ) , 8 weeks after the last infusion , at which stage disease flares were reported by some subjects . MRI showed that the mean number of lesions resolving for each subject from week 0 to week 30 was significantly greater in the combination group than in the methotrexate monotherapy group ( p = 0.016 ) . Conclusions : Infliximab in combination with methotrexate was a safe and efficacious treatment in AS over 6 months and was associated with significant regression in enthesitis/osteitis as determined by MRI . However , disease flares were reported 8 weeks after the last infusion , indicating that addition of methotrexate failed to extend the infliximab dosing interval Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVES To study the long-term efficacy and safety of treatment with infliximab in patients with ankylosing spondylitis ( AS ) in a real life setting . METHODS AS patients from 6 European countries who had finished the 2-year trial ASSERT were invited to participate in the open- label investigator-driven study EASIC . At baseline , 2 groups were formed : patients of group 1 had not been treated with infliximab after ASSERT , while those of group 2 had continuously received it . Patients of group 1 were further subdivided in group 1a : patients with a relapse and 1b : in remission . All patients of group 1a and 2 continuously received infliximab for 96 weeks , mean dose 5 mg/kg , intervals 6 - 8 weeks . Patients of group 1b were also treated in case of relapse . RESULTS A total of 103/149 patients ( 69 % ) were included in EASIC , 1.3 ± 0.9 years after the end of ASSERT : 9 in group 1a , 5 in group 1b and 89 in group 2 . Most patients were male ( 83 % ) , mean age 44 years . Most patients of group 2 completed the trial ( 86 % ) vs. only 5 of group 1 ( 33 % ) - mostly due to allergic reactions after readministration of infliximab . In total , there were 22 drop-outs due to 6 adverse events , 4 lack of efficacy , 3 planned pregnancy . All st and ard assessment s indicated beneficial values over time , at week 96 significantly better than at baseline of ASSERT . CONCLUSIONS The majority of patients were continuously and successfully treated with infliximab for 5 years , whereas discontinuation and re introduction of therapy was less satisfactory due to the frequent occurrence of hypersensitivity reactions . Anti-TNF therapy with infliximab proved to be effective and safe on a long-term basis Objective : To vali date and refine two sets of c and i date criteria for the classification/diagnosis of axial spondyloarthritis ( SpA ) . Methods : All Assessment of SpondyloArthritis international Society ( ASAS ) members were invited to include consecutively new patients with chronic ( ⩾3 months ) back pain of unknown origin that began before 45 years of age . The c and i date criteria were first tested in the entire cohort of 649 patients from 25 centres , and then refined in a r and om selection of 40 % of cases and thereafter vali date d in the remaining 60 % . Results : Upon diagnostic work-up , axial SpA was diagnosed in 60.2 % of the cohort . Of these , 70 % did not fulfil modified New York criteria and , therefore , were classified as having “ non-radiographic ” axial SpA. Refinement of the c and i date criteria result ed in new ASAS classification criteria that are defined as : the presence of sacroiliitis by radiography or by magnetic resonance imaging ( MRI ) plus at least one SpA feature ( “ imaging arm ” ) or the presence of HLA-B27 plus at least two SpA features ( “ clinical arm ” ) . The sensitivity and specificity of the entire set of the new criteria were 82.9 % and 84.4 % , and for the imaging arm alone 66.2 % and 97.3 % , respectively . The specificity of the new criteria was much better than that of the European Spondylarthropathy Study Group criteria modified for MRI ( sensitivity 85.1 % , specificity 65.1 % ) and slightly better than that of the modified Amor criteria ( sensitivity 82.9 , specificity 77.5 % ) . Conclusion : The new ASAS classification criteria for axial SpA can reliably classify patients for clinical studies and may help rheumatologists in clinical practice in diagnosing axial SpA in those with chronic back pain . Trial registration number : NCT00328068 Introduction In clinical practice , nonsteroidal anti-inflammatory drugs ( NSAIDs ) are commonly discontinued after response to biologic therapy is achieved in patients with axial spondyloarthritis ( axSpA ) , but the impact of NSAID discontinuation has not been assessed in prospect i ve controlled trials . The aim of the SPARSE study was to evaluate the effects of the anti-tumor necrosis factor agent etanercept on NSAID intake and conventional clinical outcomes in axSpA patients . Methods In the double-blind , placebo-controlled period , patients with active ( mini Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) ≥4 ) axSpA despite optimal NSAID intake were r and omized to receive etanercept 50 mg or placebo once weekly for 8 weeks . All patients were advised to taper/discontinue their NSAID intake during the treatment period . NSAID intake was self-reported by diary and Assessment of SpondyloArthritis International Society (ASAS)-NSAID scores calculated based on ASAS recommendations . The primary endpoint was change from baseline to week 8 in ASAS-NSAID score ( analysis of covariance ) . Results In 90 r and omized patients at baseline , mean age ( st and ard deviation ) was 38.9 ( 11.8 ) years ; disease duration , 5.7 ( 8.1 ) years ; 59/90 ( 66 % ) were human leukocyte antigen-B27 positive ; 51/90 ( 57 % ) had radiographic sacroiliitis ; and 45/90 ( 50 % ) were magnetic resonance imaging sacroiliitis-positive . Mean ASAS-NSAID scores were similar between etanercept and placebo groups at baseline ( 98.2 ( 39.0 ) versus 93.0 ( 23.4 ) ) , as were BASDAI ( 6.0 ( 1.7 ) versus 5.9 ( 1.5 ) ) , and Bath Ankylosing Spondylitis Functional Index ( 5.2 ( 2.1 ) versus 5.1 ( 2.2 ) ) . Mean changes ( SE ) in ASAS-NSAID score from baseline to week 8 were –63.9 ( 6.1 ) and –36.6 ( 5.9 ) in the etanercept and placebo groups ( between-group difference , –27.3 ; P = 0.002 ) . Significantly higher proportions of patients receiving etanercept versus placebo had an ASAS-NSAID score < 10 ( 46 % versus 17 % ; P = 0.008 ) and ASAS-NSAID score of 0 ( 41 % versus 14 % ; P = 0.013 ) at this time point . Significantly more patients in the etanercept versus placebo group achieved BASDAI50 ( 39 % versus 18 % ; P = 0.032 ) and ASAS40 ( 44 % versus 21 % ; P = 0.028 ) at week 8 . Conclusions In patients with axSpA , etanercept was associated with clinical ly relevant NSAID-sparing effects in addition to significant improvements in conventional clinical outcomes .Trial registration Clinical Trials.gov NCT01298531 . Registered 16 February 2011 Objective To evaluate radiographic progression in patients with ankylosing spondylitis ( AS ) receiving two different doses of the tumour necrosis factor antagonist golimumab . Methods 356 patients with AS were r and omly assigned to placebo , or golimumab 50 mg or 100 mg every 4 weeks ( wks ) . At wk16 , patients with inadequate response early escaped with blinded dose adjustments ( placebo→golimumab 50 mg , 50 mg→100 mg ) . At wk24 , patients still receiving placebo crossed over to golimumab 50 mg . Lateral view radiographs of the cervical/lumbar spine were obtained at wk0 , wk104 and wk208 , and scored ( two blinded readers , modified Stoke AS Spine Score ( mSASSS ) ) . Observed data were used for wk104 analyses ; missing wk208 scores were linearly extrapolated . Results Wk104 changes from baseline in mSASSS averaged 1.6±4.6 for placebo crossover , 0.9±2.7 for 50 mg and 0.9±3.9 for 100 mg . By wk208 , following golimumab therapy for 3.5–4 years , mean changes in mSASSS were 2.1±5.2 for placebo crossover , 1.3±4.1 for 50 mg and 2.0±5.6 for 100 mg . Less than a third of patients ( placebo crossover , 19/66 ( 28.8 % ) ; 50 mg , 29/111 ( 26.1 % ) ; 100 mg , 35/122 ( 28.7 % ) ) had a definitive change from baseline mSASSS ( > 2 ) . Less radiographic progression was observed through wk208 in patients without baseline syndesmophytes ( 0.2 vs 2.8 in patients with ≥1 syndesmophyte ; p<0.0001 ) and with baseline C-reactive protein ( CRP ) levels ≤1.5 mg/dl ( 0.9 vs 2.9 with CRP > 1.5 mg/dl ; p=0.0004 ) . Conclusions No difference in mSASSS change was observed between golimumab 50 mg and 100 mg . The radiographic progression rate remained stable at years 2 and 4 , suggesting no acceleration of new bone formation over time . Golimumab-treated AS patients with no syndesmophytes and less systemic inflammation at baseline had considerably less radiographic progression Objective To assess the effectiveness of switching to a second tumour necrosis factor inhibitor ( TNFi ) in patients with ankylosing spondylitis ( AS ) . Methods Data were extracted from an ongoing longitudinal observational multicentre study in Norway . This study included  anti-TNF naïve patients with AS starting treatment with a TNFi as well as treatment with a second TNFi in these same patients .  Effectiveness data and 2-year drug survival were compared between switchers and non-switchers and within switchers ( first and second TNFi ) . Results 514 anti-TNF naïve patients with AS were included ; 77 patients switched to a second TNFi while 437 patients did not switch . The percentages of non-switchers using etanercept , infliximab or adalimumab  were 53 % , 32 % and 15 % , and the percentages of first and second TNFi in the switchers were 42 % , 53 % and 5 % and 40 % , 23 % and 36 % , respectively . The reason for switching was insufficient response ( IR ) in 30 , adverse events ( AEs ) in 44 and not reported in 3 patients . Baseline disease activity was similar between the groups . Three-month BASDAI 50 and ASAS 40 responses were achieved by 49 % and 38 % of non-switchers , by 25 % and 30 % of switchers after the first TNFi and by 28 % and 31 % after the second TNFi . The 3-month disease activity level was higher for switchers on the second TNFi than for non-switchers . Drug withdrawal rate was higher during the second TNFi among switchers than for non-switchers ( p=0.001 ) . No difference was found in the effectiveness of the second TNFi between switchers due to IR and AE . Conclusion This study confirms that switching to a second TNFi can be effective in AS and can be as useful as in rheumatoid arthritis , although overall effectiveness seems to be somewhat lower than in non-switchers OBJECTIVE To evaluate the short-term efficacy and safety of etanercept treatment in Chinese patients with active ankylosing spondylitis ( AS ) . METHODS This was a 12-week multicenter , double-blind , placebo-controlled , r and omized phase III clinical study . The first part was a 6-week placebo-controlled period followed by a 6-week open-label period . The primary efficacy endpoint was the percentage of subjects achieving a 20 % improvement in assessment in ankylosing spondylitis ( ASAS ) ( ASAS 20 ) . The secondary efficacy endpoints were the percentage of patients achieving a 40 % improvement in ASAS ( ASAS 40 ) , achieving a 50 % improvement in ASAS ( ASAS 50 ) , achieving a 70 % improvement in ASAS ( ASAS 70 ) , and ASAS 5/6 responses at all visits , and the improvement in subject global assessment , physician global assessment , nocturnal and total back pain , bath AS functional index ( BASFI ) , bath AS disease activity index ( BASDAI ) , spinal mobility , joint assessment and quality of life assessment . All subjects in the study were evaluated for safety . RESULTS The primary endpoint , ASAS 20 at week 6 , was achieved by 86.5 % ( 64/74 ) patients in the etanercept group compared to 29.5 % ( 23/78 ) patients in the placebo group ( P < 0.001 ) . As early as week 2 , the percentages of patients achieving the ASAS 20 between the two groups were significantly different . Furthermore , the majority of secondary efficacy end points were also significantly improved . Most of adverse events ( AE ) were mild in nature , the commonest adverse events were elevated liver function levels , injection site reactions and nasopharyngitis . No death or serious AE were observed . CONCLUSION Etanercept can improve symptoms fastly , significantly and safely in Chinese patients with active AS OBJECTIVE Evaluate long-term safety and efficacy of etanercept treatment in patients with ankylosing spondylitis ( AS ) . METHODS Patients with AS who previously participated in a r and omised controlled trial ( RCT ) of etanercept  were eligible to enroll in a 168-week open-label extension ( OLE ) . Safety end points included rates of adverse events ( AE ) , serious adverse events ( SAE ) , infections , serious infections and death . Efficacy end points included Assessment in Ankylosing Spondylitis ( ASAS20 ) response , ASAS 5/6 response and partial remission rates . RESULTS A total of 257 of 277 patients ( 92 % ) enrolled in the OLE . After up to 192 weeks of treatment with etanercept , the most common AEs were injection site reactions , headaches and diarrhoea . The exposure-adjusted rate of SAEs was 0.08 per patient-year . The rate of infections was 1.1 per patient-year , and the rate for serious infections was 0.02 per patient-year . No deaths were reported . Of patients who received  etanercept  in both the RCT and OLE and were still in the trial , 71 % were ASAS20 responders at week 96 , and 81 % were responders at week 192 . ASAS 5/6 response rates were 61 % at week 96 and 60 % at week 144 , and partial remission response rates were 41 % at week 96 and 44 % at week 192 . Placebo patients who switched to etanercept in the OLE showed similar patterns of efficacy maintenance . CONCLUSIONS Etanercept was well tolerated for up to 192 weeks in patients with AS , with no unexpected AEs or SAEs observed . No deaths were reported . Improvements in the signs and symptoms of AS were maintained for up to 192 weeks Objective Assess golimumab efficacy/safety through 5 years in patients with active ankylosing spondylitis ( AS ) . Methods 356 patients with AS were r and omly assigned to placebo , golimumab 50 mg or 100 mg every 4 weeks . At week 16 , patients with inadequate response early escaped with blinded dose adjustments ( placebo to 50 mg , 50 mg to 100 mg ) . At week 24 , all patients receiving placebo crossed over to 50 mg . Blinded active therapy continued through week 104 ; from week 104 to week 252 , the golimumab dose could be adjusted . Intent-to-treat and observed efficacy data were assessed by r and omised treatment groups . Results At week 256 , and with > 4.5 years of golimumab , overall intent-to-treat Assessment in SpondyloArthritis international Society criteria for 20 % improvement ( ASAS20 ) and ASAS40 response rates were 66.0 % ( 235/356 ) and 57.0 % ( 203/356 ) , respectively ; Bath AS Disease Activity Index 50 % improvement response was 55.9 % ( 199/356 ) . Observed response rates among the 255 ( 72 % ) patients who continued golimumab through week 252 were consistent , albeit somewhat higher . Among patients who increased golimumab from 50 to 100 mg , 60.6 % ( 20/33 ) and 44.7 % ( 17/38 ) achieved ASAS20/ASAS40 responses , respectively , following ≥2 consecutive doses of golimumab 100 mg . Golimumab safety through week 268 was similar to that through week 24 regardless of dose . Conclusions Clinical improvements observed in patients treated with golimumab through week 24 were sustained through week 256 ( 5 years ) . Long-term golimumab safety is consistent with that of other established tumour-necrosis-factor-antagonists . Trial registration number Clinical Trials.gov : NCT00265083 Objectives To evaluate the efficacy and safety of certolizumab pegol ( CZP ) after 24 weeks in RAPID-axSpA ( NCT01087762 ) , an ongoing Phase 3 trial in patients with axial spondyloarthritis ( axSpA ) , including patients with ankylosing spondylitis ( AS ) and non-radiographic axSpA ( nr-axSpA ) . Methods Patients with active axSpA were r and omised 1:1:1 to placebo , CZP 200 mg every 2 weeks  ( Q2W ) or  CZP 400 mg every 4 weeks ( Q4W ) . In total 325 patients were r and omised . Primary endpoint was ASAS20 ( Assessment of SpondyloArthritis international Society 20 ) response at week 12 . Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index ( BASFI ) , Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , and Bath Ankylosing Spondylitis Metrology Index ( BASMI ) linear . Results Baseline disease activity was similar between AS and nr-axSpA. At week 12 , ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo ( 57.7 and 63.6 vs 38.3 , p≤0.004 ) . At week 24 , combined CZP arms showed significant ( p<0.001 ) differences in change from baseline versus placebo in BASFI ( −2.28 vs −0.40 ) , BASDAI ( −3.05 vs −1.05 ) , and BASMI ( −0.52 vs −0.07 ) . Improvements were observed as early as week 1 . Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA sub population s. Adverse events were reported in 70.4 % vs 62.6 % , and serious adverse events in 4.7 % vs 4.7 % of All CZP versus  placebo groups . No deaths or malignancies were reported . Conclusions CZP rapidly reduced the signs and symptoms of axSpA , with no new safety signals observed compared to the safety profile of CZP in RA . Similar improvements were observed across CZP dosing regimens , and in AS and nr-axSpA patients Abstract Objective : To measure the health of a representative sample of the population of the United Kingdom by using the EuroQoL EQ-5D question naire . Design : Stratified r and om sample representative of the general population aged 18 and over and living in the community . Setting : United Kingdom . Subjects : 3395 people resident in the United Kingdom . Main outcome measures : Average values for mobility , self care , usual activities , pain or discomfort , and anxiety or depression . Results : One in three respondents reported problems with pain or discomfort . There were differences in the perception of health according to the respondent 's age , social class , education , housing tenure , economic position , and smoking behaviour . Conclusions : The EQ-5D question naire is a practical way of measuring the health of a population and of detecting differences in subgroups of the population . Key messages Measurement of health outcome requires the observation of states of health Patients ' involvement in recording and assessing their own state of health is a major element in the process of evaluating the impact of health care The EuroQoL EQ-5D question naire highlights variations in states of health which are consistent with previously published results High degrees of pain are reported in the general population . A category for pain is absent and thus undetected in the survey of disability by the Office of Population Censuses and OBJECTIVE To assess safety and efficacy of infliximab in patients with ankylosing spondylitis ( AS ) through 102 weeks . METHODS Patients ( n = 279 ) with active AS were r and omized to either group 1 ( n = 78 ; placebo through week 24 and then infliximab 5 mg/kg from weeks 24 through 96 ) or group 2 ( n = 201 ; infliximab 5 mg/kg through week 96 ) . The primary efficacy end point at week 24 ( > or=20 % improvement in the ASsessment in Ankylosing Spondylitis International Working Group criteria [ ASAS20 ] ) was assessed with an intent-to-treat analysis of observed data . RESULTS More patients in group 2 than group 1 achieved the ASAS20 response at week 24 ( 61.2 % versus 19.2 % ; P < 0.001 ) . By week 102 , groups 1 and 2 were similar with regard to ASAS20 response ( 72.1 % versus 73.9 % ) ; ASAS40 responses at week 102 were 45.9 % versus 59.4 % . No new safety issues were discerned . CONCLUSION Infliximab demonstrated sustained efficacy and safety over 2 years in this large cohort of patients with active AS The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials . The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label r and omised study . Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group . Treatment with both etanercept and infliximab at the end of the study was effective , safe , and well tolerated OBJECTIVE To study the effect of tumor necrosis factor α ( TNFα ) inhibitors on  progressive spinal damage in patients with ankylosing spondylitis ( AS ) . METHODS All AS patients meeting the modified New York criteria who had been monitored prospect ively and had at least 2 sets of spinal radiographs a minimum of 1.5 years apart were included in the study ( n=334 ) . The patients received st and ard therapy , which included nonsteroidal antiinflammatory drugs and TNFα inhibitors . Radiographic severity was assessed by the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Patients with a rate of AS progression that was ≥1 mSASSS unit/year were considered progressors . Univariable and multivariable regression analyses were done . Propensity score matching and sensitivity analysis were performed . A zero-inflated negative binomial ( ZINB ) model was used to analyze the effect of TNFα inhibitors on the change in the mSASSS with varying followup periods . Potential confounders , such as disease activity ( as assessed by the Bath Ankylosing Spondylitis Disease Activity Index ) , the erythrocyte sedimentation rate , C-reactive protein level , HLA-B27 positivity , sex , age at onset , smoking burden ( number of pack-years ) , and baseline damage , were included in the model . RESULTS TNFα inhibitor treatment was associated with a 50 % reduction in the odds of progression , with an odds ratio ( OR ) of 0.52 ( 95 % confidence interval [ 95 % CI ] 0.30 - 0.88 , P=0.02 ) . Patients with a delay of > 10 years in starting therapy were more likely to experience progression as compared to those who started earlier ( OR 2.4 [ 95 % CI 1.09 - 5.3 ] , P=0.03 ) . In the ZINB model , the use of TNFα inhibitors  significantly reduced disease progression when the gap between radiographs was > 3.9 years . The protective effect of TNFα inhibitors was stronger after propensity score matching . CONCLUSION Treatment with TNFα inhibitors appears to reduce radiographic progression in AS patients , especially with early initiation and with longer duration of followup UNLABELLED BACKGROUND Treatment options for patients with ankylosing spondylitis are few . We aim ed to assess the effectiveness of infliximab , an antibody to tumour necrosis factor (TNF)-alpha , in treatment of such patients . METHODS In this 12-week placebo-controlled multicentre study , we r and omly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab ( 5 mg/kg ) and 35 to placebo at weeks 0 , 2 , and 6 . One patient in the infliximab group was withdrawn from the study . Our primary outcome was regression of disease activity of at least 50 % . To assess response , we used vali date d clinical criteria from the ankylosing spondylitis assessment working group , including disease activity ( BASDAI ) , functional indices ( BASFI ) , metrology ( BASMI ) , and quality of life ( short form 36 ) . Analyses were done by intention to treat . FINDINGS 18 ( 53 % ) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50 % compared with three ( 9 % ) of 35 on placebo ( difference 44 % [ 95 % CI 23 - 61 ] , p<0.0001 ) . Function and quality of life also improved significantly on infliximab but not on placebo ( p<0.0001 and p<0.0001 , respectively ) . Treatment with infliximab was generally well tolerated , but three patients had to stop treatment because of systemic tuberculosis , allergic granulomatosis of the lung , or mild leucopenia . INTERPRETATION Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis . Since there are some potentially serious adverse effects , we recommend that this treatment mainly be used in co-operation with rheumatological centres OBJECTIVE The aim of this study was to assess the efficacy and safety of golimumab in Chinese patients with active AS . METHODS Two hundred and thirteen patients were r and omized in a 1:1 ratio to receive either s.c . injections of placebo from weeks 0 to 20 followed by golimumab 50 mg from weeks 24 to 48 ( group 1 , n = 105 ) or golimumab 50 mg from weeks 0 to 48 ( group 2 , n = 108 ) , both every 4 weeks . Placebo crossover occurred at week 24 , while early escape was at week 16 . The primary endpoint was an improvement of at least 20 % in the Assessment of SpondyloArthritis international Society ( ASAS20 ) criteria at week 14 . Major secondary endpoints included week 24 ASAS20 response and week 14 change scores for BASFI and BASMI . RESULTS Golimumab treatment elicited significantly better responses than placebo in week 14 ASAS20 response [ 49.1 % ( 53/108 ) vs 24.8 % ( 26/105 ) , respectively , P < 0.001 ] , week 24 ASAS20 response ( 50.0 % vs 22.9 % , P < 0.001 ) and mean improvements in BASFI ( -1.26 vs 0.11 , P < 0.001 ) and BASMI ( -0.42 vs -0.19 , P = 0.021 ) scores at week 14 . Additionally , golimumab treatment led to significant improvements in the mental and physical components of health-related quality of life ( HRQoL ) and sleep problems at week 24 , all of which were further improved through week 52 . During the 16-week placebo-controlled study period , 31.4 % and 30.6 % of patients had adverse events ( AEs ) in groups 1 and 2 , respectively ; similar AE reporting rates were observed through week 24 ( 34.3 % and 32.0 % ) and among the golimumab-treated patients through week 56 ( 41.2 % ) . CONCLUSION Golimumab significantly reduced clinical symptoms/signs and improved physical function , range of motion and HRQoL in Chinese patients with active AS without unexpected safety concerns . TRIAL REGISTRATION Clinical Trials.gov , NCT01248793 OBJECTIVE To 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 Abstract : The aim of the study was to analyse the 2-year follow-up of a series of patients with the diagnosis of undifferentiated spondyloarthropathy ( uSpA ) . A prospect i ve study was carried out analysing 68 patients with symptomatic uSpA who fulfilled the European Spondylarthropathy Study Group ( ESSG ) criteria for seronegative spondyloarthropathies ( SpA ) and were aged between 18 and 50 years . Inclusion criteria included inflammatory low back pain ( ILBP ) ( without radiographic sacroiliitis ) , asymmetric oligoarthritis ( predominantly affecting large joints in the lower limbs ) and heel enthesopathies ( Achilles tendinitis and /or plantar fasciitis ) . Imaging methods included pelvic radiography ( at study entry and after 2 years ) and calcaneal radiography ( at study entry ) . There was a predominance of male gender ( 78 % ) , caucasoid race ( 72 % ) and positive HLA-B27 ( 54 % ) , with a mean age of 31 years and mean disease duration of 5 years . The first disease manifestations were ILBP ( 49 % ) , asymmetric oligoarthritis ( 35 % ) and heel enthesopathies ( 16 % ) . A positive family history of a definite SpA was mentioned by 9 % of the patients . Seventeen patients ( 25 % ) scored 5 points in the Amor set of SpA criteria ; logistic regression analysis showed that HLA-B27 , heel enthesopathy and asymmetric oligoarthritis were significantly associated with Amor criteria ≥6 , whereas ILBP was associated with Amor criteria < 6 . Male sex was associated with heel enthesopathies ( p = 0.041 ) and ankle involvement ( p = 0.015 ) . Caucasoid race was associated with ILBP ( p = 0.015 ) and buttock pain ( p = 0.047 ) . Positive HLA-B27 was associated with wrist involvement ( p = 0.019 ) and Amor criteria ≥6 ( p = 0.001 ) . After a 2-year follow-up the following outcomes were observed : uSpA 75 % ; disease remission 13 % ; ankylosing spondylitis 10 % ; psoriatic arthritis 2 % . Logistic regression analysis showed that buttock pain and positive HLA-B27 ( trend ) were statistically associated with progression to a definite SpA. In conclusion , uSpA can represent a provisional diagnosis in the group of SpA and a systematic follow-up is necessary in order to better establish the different patterns of the disease OBJECTIVE To evaluate the effect of adalimumab on pain , fatigue , and stiffness in patients with active ankylosing spondylitis ( AS ) . METHODS The Adalimumab Trial Evaluating Long-Term Safety and Efficacy for Ankylosing Spondylitis ( ATLAS ) was an ongoing 5-year study that included an initial 24-week , r and omized , placebo-controlled , double-blind period . Patients were r and omized to adalimumab 40 mg or placebo by subcutaneous injection every other week . Pain was assessed by the bodily pain domain scores of the Medical Outcomes Study Short Form-36 Health Survey ( SF-36 ) and also by total back pain and nocturnal pain using visual analog scales . Fatigue was measured by the SF-36 vitality domain and question 1 of the Bath AS Disease Activity Index ( BASDAI ) . Morning stiffness was measured by the mean of BASDAI questions 5 and 6 . RESULTS Of 315 patients enrolled , 208 received adalimumab 40 mg and 107 received placebo .  At Week 12 , adalimumab-treated patients experienced significant improvement compared with placebo-treated patients in the SF-36 bodily pain score ( p < 0.001 ) , total back pain score ( p < 0.001 ) , nocturnal pain score ( p < 0.001 ) , fatigue ( p < 0.01 ) , and morning stiffness ( p < 0.001 ) . Pain , fatigue , and morning stiffness were significantly correlated ( p < 0.001 ) with baseline values of patient-reported health-related quality of life ( HRQOL ) , and physical function , and with improvements in these values at Week 12 by regression analysis . Treatment effects occurred rapidly ( within 2 wks ) and were maintained through 24 weeks of treatment . CONCLUSION Adalimumab significantly improved symptoms of pain , fatigue , and stiffness  in patients with AS . Improved symptoms were associated with improved physical function and HRQOL OBJECTIVE Treatment of ankylosing spondylitis ( AS ) with infliximab , an anti-tumor necrosis factor alpha monoclonal antibody , was shown to be efficacious in patients with active disease during a 3-month treatment period . The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period . METHODS This study was an open , observational , extension study of a 3-month , r and omized , placebo-controlled trial . All patients who had tolerated infliximab ( infliximab/infliximab group ) or placebo ( placebo/infliximab 12-week crossover group ) therapy for 3 months entered the open extension trial ( n = 65 ) .  Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase ( weeks 0 , 2 , and 6 ) . The primary end point was a 50 % improvement in the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) . RESULTS At week 54 , a total of 54 of the 69 patients ( 78 % ) continued to take infliximab . The intent-to-treat primary efficacy analysis at week 54 showed that 47 % of patients in the infliximab/infliximab group ( 95 % confidence interval 31 - 63 ) and 51 % of the patients in the placebo/infliximab group ( 95 % confidence interval 36 - 67 ) achieved 50 % improvement in BASDAI scores . In the analysis of those who completed the study , the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups : from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group . The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70 % of the patients . There were significant improvements in measures of functioning , metrologic parameters , and quality of life . Between weeks 12 and 54 , a total of 4 patients had serious adverse events that were possibly related to infliximab and result ed in their discontinuing the study . CONCLUSION Infliximab therapy in AS patients result ed in a rapid and significant improvement in BASDAI scores ( > 50 % improvement ) and a durable response for 1 year . The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications OBJECTIVE Infliximab , a monoclonal antibody against tumour necrosis factor alpha ( TNF-alpha ) , is approved in Europe for the treatment of patients with active ankylosing spondylitis ( AS ) who have responded inadequately to conventional therapy . This report provides analyses from a 3-yr extension study , as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month r and omized controlled trial of infliximab in patients with AS . METHODS Of the 49 patients with AS who completed the second year of the study , 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156 . The Bath AS Disease Activity Index ( BASDAI ) , the Bath AS Functional Index , the Bath AS Metrology Index , patient 's and physician 's global assessment s , quality of life ( Short Form-36 ) , C-reactive protein ( CRP ) and erythrocyte sedimentation rate were assessed throughout the study period . RESULTS The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study . Forty-three patients ( 62 % of the 69 patients enrolled at baseline and 93 % of the patients who started the third year ) completed week 156 . In the intention-to-treat analysis , an ASAS ' 5 out of 6 ' and ASAS 40 % response was seen by 46 % and 50 % of the patients , respectively . The scores for other efficacy assessment s were similar to the values observed at weeks 54 and 102 . Median CRP levels remained low ( 1.5 mg/l at week 156 ) . There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study . CONCLUSIONS Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy . Long-term infliximab treatment was well tolerated by patients in this study A key component of the Cochrane Collaboration 's risk of bias tool for critically evaluating r and omised trials is the consideration of whether baseline characteristics of the treatment groups being compared are systematic ally different . Considered under the domain of ' selection bias ' , this is currently evaluated by looking at the methods of r and omisation and specifically at the generation of the r and omised allocation sequence and the concealment of this sequence during the process of r and omisation . Assessment of the actual similarity of baseline variables across groups in demographic and clinical characteristics is seldom performed . Even when performed , the link with selection bias is sometimes not considered . Methods of r and omisation and allocation concealment are often poorly reported in published trials , yet baseline data tables are presented in a large majority of trial reports . In this article , we propose that assessment of trial baseline data should form a key and prominent part of selection bias judgements when using the risk of bias tool . We outline the possible benefits from using this approach , including reduced uncertainty in systematic review conclusions , reduced risk of chance findings being ascribed to treatment effects and better use of available evidence by a more considered approach to evaluating studies using imperfect r and omisation and allocation methods OBJECTIVES To describe the healthcare re source use and productivity losses associated with patients with ankylosing spondylitis ( AS ) and explore the relationship between disease severity and total costs . METHODS A cross-sectional postal survey was conducted on a sample of 1,000 patients with AS r and omly selected from registries at 10 secondary care rheumatology centres in the UK .  Information on demographic characteristics , disease and functional activity , healthcare use and work status ( presenteeism and absenteeism ) during the previous three months was collected . The relationship between disease severity and total costs was explored using a two-part regression model , controlling for age , gender and disease duration and vali date d on respondents ( n=470 ) of the second round of the survey . RESULTS Respondents at baseline ( n=612 ) covered the full spectrum of AS , had a mean BASDAI of 4.6 and 55.3 % of individuals scored at least 4 on the BASDAI scale . The mean ( median ) three month total cost was £ 2,802 ( £ 1,160 ) . Both physical function and disease activity were significant predictors of total costs . Mean ( median ) three month total costs for patients with BASDAI < 4 , 4 - 6 and > 6 were £ 1,331 ( £ 502 ) , £ 2,790 ( £ 1,281 ) and £ 4,840 ( £ 5,017 ) respectively . Direct National Health Service funded healthcare costs contributed to just 15 % of total costs while unemployment , absenteeism from work and reduced productivity at work accounted for 63.2 % , 1.4 % and 19.0 % of total costs , respectively . CONCLUSIONS This study shows that direct healthcare costs alone do not describe the total costs associated with AS and that productivity losses associated with AS are considerable OBJECTIVE To investigate the effect of etanercept therapy on radiographic progression in patients with ankylosing spondylitis ( AS ) . METHODS Patients with AS who had previously participated in a 24-week r and omized , double-blind , placebo-controlled trial of etanercept therapy were enrolled in a 72-week open-label extension . Radiographs of the cervical and lumbar spine from patients who received etanercept ( 25 mg twice weekly ) for up to 96 weeks were compared with radiographs from patients in a large prevalence cohort ( Outcome Assessment s in Ankylosing Spondylitis International Study [ OASIS ] ) who had not been treated with anti-tumor necrosis factor alpha ( anti-TNFalpha ) agents . Radiographs obtained at 2 time points up to 96 weeks apart from patients in both study population s were digitized and read by 2 independent readers who were blinded with regard to patient group and sequence . The primary end point was the 96-week change in the modified Stoke AS Spine Score ( mSASSS ) . RESULTS A total of 257 patients treated with etanercept were compared with 175 unselected patients from the OASIS study . There was no significant difference in the change in the mSASSS from baseline among patients who received etanercept ( mean + /- SD 0.91 + /- 2.45 ) versus those from the OASIS group ( 0.95 + /- 3.18 ) . CONCLUSION Unlike other inflammatory rheumatic diseases such as rheumatoid arthritis and psoriatic arthritis , structural progression in AS seems to be independent of TNF , despite the fact that TNF is responsible for the signs and symptoms due to inflammation in this disease OBJECTIVE The minimum clinical ly important difference ( MCID ) is the minimum level of change of an outcome measure that is considered to be clinical ly relevant . This prospect i ve study was conducted to establish the minimum level of change in the Bath Ankylosing Spondylitis ( BAS ) indices that is meaningful for both the patient and the clinician . METHODS The BAS question naires [ i.e. , Bath Ankylosing Spondylitis Functional Index ( BASFI ) ; Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) ; and Bath Ankylosing Spondylitis patient Global score ( BAS-G ) ] were administered to 125 patients with ankylosing spondylitis ( AS ) at baseline and at the end of a 2-week intensive physiotherapy program . Together with the final assessment , a global vali date d rating scale was used to examine each domain . Receiver operating characteristic ( ROC ) curves were plotted to determine the BAS change score that most accurately classified patients with respect to a clinical ly meaningful change . This analysis was repeated to investigate whether the estimate of change was dependent upon the patients ' baseline scores . RESULTS According to analyses of ROC curves , the MCID are 7 mm or 17.5 % for BASFI : sensitivity = 0.60/specificity = 0.85 ; 10 mm or 22.5 % for BASDAI : sensitivity = 0.65/specificity = 0.82 ; and 15 mm or 27.5 % for BAS-G : sensitivity = 0.61/specificity = 0.74 . MCID values were independent of the patients ' baseline scores ( p = 0.09 to 0.72 ) by regression analysis . CONCLUSION This prospect i ve study gives MCID values for BASFI , BASDAI , and BAS-G that allow translation from the BAS indices to readily understood values for both patients and clinicians OBJECTIVE To assess the impact of ankylosing spondylitis ( AS ) on patient health-related quality of life ( HRQOL ) relative to both the general US and chronically-ill population s , and to evaluate whether etanercept therapy can reverse impairments in HRQOL due to AS . METHODS Two AS patient population s were evaluated : patients with AS from a US clinical trial who were r and omized to receive either etanercept ( n = 20 ) or placebo ( n = 20 ) for 16 weeks , and placebo-treated patients from a multinational sample who subsequently received etanercept ( n = 129 ) during a 48-week , open-label extension study . A sample from the US general population and patients with other medical conditions derived from the National Survey of Functional Health Status were used as comparators to evaluate the relative impact of active AS on HRQOL , as measured by the Short Form 36 ( SF-36 ) question naire . RESULTS At baseline , patients with AS in both the US and multinational sample s had significantly lower scores than the US general population on all 8 SF-36 scales . Compared with patients with other medical conditions , patients with AS had the lowest scores in the physical domains -- Physical Functioning , Role Physical , and Bodily Pain . Impairments in SF-36 scores for psychosocial domains , such as Social Functioning , Role Emotional , and Mental Health , were somewhat less pronounced in patients with AS . Treatment with etanercept significantly improved the HRQOL of patients with AS on all 8 SF-36 scales , especially in the same physical domains that showed the greatest impairments prior to treatment ( Physical Functioning , Role Physical , and Bodily Pain ) . CONCLUSION Patients with active AS despite conventional therapy have significantly reduced HRQOL across a wide range of domains . These reductions are most pronounced in the physical domains and exceed those seen in many other chronic diseases . Etanercept therapy significantly improves patient HRQOL , indicating that decrements in HRQOL due to AS may be at least partly reversible Objective : To compare the efficacy , pharmacokinetics and safety of etanercept 50 mg once weekly with 25 mg twice weekly and placebo in patients with ankylosing spondylitis . Methods : A 12-week , double-blind , placebo-controlled study compared the effects of etanercept 50 mg once weekly , etanercept 25 mg twice weekly and placebo in 356 patients with active ankylosing spondylitis ( 3:3:1 r and omisation , respectively ) . The primary end point was the proportion of patients achieving a response at week 12 based on the Assessment in Ankylosing Spondylitis Working Group criteria ( ASAS 20 ) . The pharmacokinetics of etanercept 50 mg once weekly and 25 mg twice weekly were analysed . Results : Baseline characteristics and disease activity were similar among the three groups : etanercept 50 mg once weekly , etanercept 25 mg twice weekly and placebo . The percentage of patients discontinuing therapy was 9.0 % , 9.3 % and 13.7 % for the three respective groups . ASAS 20 response at 12 weeks was achieved by 74.2 % of patients with etanercept 50 mg once weekly and 71.3 % of those with etanercept 25 mg twice weekly , both significantly higher than the percentage of patients taking placebo ( 37.3 % , p<0.001 ) . Percentages of patients with ASAS 5/6 response ( 70.3 % , 72.0 % and 27.5 % , respectively ; p<0.001 ) and those with ASAS 40 response ( 58.1 % , 53.3 % and 21.6 % , respectively ; p<0.001 ) followed a similar pattern . Significant improvement ( p<0.05 ) was seen in measures of disease activity , back pain , morning stiffness and C reactive protein levels as early as 2 weeks . Serum etanercept exposure was similar between the etanercept groups . Incidence of treatment-emergent adverse events , including infections , was similar among all three groups , and no unexpected safety issues were identified . Conclusions : Patients with ankylosing spondylitis can expect a comparable significant improvement in clinical outcomes with similar safety when treated with etanercept 50 mg once weekly or with 25 mg twice weekly Objective . We evaluated the effectiveness and safety of adalimumab in a large cohort of patients with active ankylosing spondylitis ( AS ) and identified clinical predictors of good clinical response . Methods . Patients with active AS [ Bath AS Disease Activity Index ( BASDAI ) ≥4 ] received adalimumab 40 mg every other week in addition to their st and ard antirheumatic therapies in a multinational 12-week , open-label study . We used 3 definitions of good clinical response : 50 % improvement in the BASDAI ( BASDAI = 50 ) , 40 % improvement in the ASsessment s of SpondyloArthritis International Society criteria ( ASAS40 ) , or ASAS partial remission . Response predictors were determined by logistic regression with backward elimination ( selection level 5 % ) . Results . Of 1250 patients , 1159 ( 92.7 % ) completed 12 weeks of adalimumab treatment . At Week 12 , 57.2 % of patients achieved BASDAI 50 , 53.7 % achieved ASAS40 , and 27.7 % achieved ASAS partial remission . Important predictors of good clinical response ( BASDAI 50 , ASAS40 , and partial remission ) were younger age ( p < 0.001 ) , and greater C-reactive protein ( CRP ) concentration ( p ≤ 0.001 ) , HLA-B27 positivity ( p ≤ 0.01 ) , and tumor necrosis factor ( TNF ) antagonist naivety ( p < 0.001 ) . Conclusion . Adalimumab was effective in this large cohort of patients with AS , with more than half of patients achieving a BASDAI 50 or ASAS40 response and more than a quarter of patients reaching partial remission at Week 12.Younger age , greater CRP concentrations , HLA-B27 positivity , and TNF antagonist naivety were strongly associated with BASDAI 50 , ASAS40 , and partial remission responses . Clinical Trials.gov identifier : NCT00478660 OBJECTIVES To report for the first time on the efficacy and safety of anti-TNF therapy after 8 years of follow-up in patients with active AS , and analyse possible short-term predictors for long-term clinical outcomes . METHODS In this open-label extension of a r and omized controlled trial , proportions of the initially included 69 patients with active AS were treated with infliximab 5 mg/kg i.v./6 weeks for 8 years . The last report was published after 5 years . All analyses were based on completers . RESULTS Overall , 33 ( 48 % ) patients completed 8 years . Their mean ( s.d . ) BASDAI [ 2.6 ( 1.9 ) ] , BASFI [ 3.3 ( 2.6 ) ] and BASMI [ 2.7 ( 2.4 ) ] remained low at Year 8 . At the end of Year 8 , most patients were either in partial remission ( n = 8 , 24 % ) or had low disease activity ( BASDAI < 3 ; n = 21 , 64 % ) . No new serious adverse events occurred within the past 3 years . Adverse events were the most frequent reason for dropout ( 56 % ) . There were no differences between completers and dropouts at baseline , but the latter had higher BASFI values at dropout . No baseline parameter was associated with good long-term response to infliximab , but lower BASDAI levels after 12 weeks were predictive of a higher probability of partial remission [ odds ratio ( OR ) 2.9 , 95 % CI 1.3 , 6.3 , P = 0.007 ] , low disease activity ( OR 1.7 , 95 % CI 1.2 , 2.3 , P = 0.005 ) or remaining on treatment ( OR 0.79 , 95 % CI 0.61 , 1.01 , P = 0.06 ) after 8 years . CONCLUSION Almost half of the initially treated patients remained on anti-TNF therapy for 8 years , and almost 90 % were in partial remission or had low disease activity . Short-term response ( low BASDAI at 3 months ) is predictive of outcome after 8 years . Infliximab therapy was safe over 8 years Objective To study the relationship between spinal mobility , radiographic damage of the spine and spinal inflammation as assessed by MRI in patients with ankylosing spondylitis ( AS ) . Methods In this sub analysis of the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy cohort , 214 patients , representing an 80 % r and om sample , were investigated . Only baseline data were used . MRI inflammation was assessed by the AS spinal MRI activity ( ASspiMRI-a ) score , structural damage by the modified Stoke AS Spine Score ( mSASSS ) and spinal mobility by the linear definition of the Bath Ankylosing Spondylitis Metrology Index ( BASMI ) . Univariate correlations were calculated on baseline values using Spearman rank correlation . Independent associations between the variables of interest were investigated by multivariate linear regression analysis . Associations with clinical disease activity , C-reactive protein , disease duration , age , gender , body mass index and HLA-B27 status were also investigated . Subanalyses were performed according to disease duration . Results BASMI correlated moderately well with mSASSS ( Spearman 's ρ=0.6 ) and weakly with ASspiMRI-a ( ρ=0.3 ) . A best-fit model for BASMI included both mSASSS ( regression coefficient (B)=0.865 , p<0.001 ) and ASspiMRI-a ( B=0.236 , p=0.018 ) . In patients with a disease duration ≤3 years , B was greater for ASspiMRI-a than for mSASSS ( 0.595 vs 0.380 ) , while in patients with a disease duration > 3 years B was greater for mSASSS than for ASspiMRI-a ( 0.924 vs 0.156 ) . Conclusion Spinal mobility impairment in AS is independently determined both by irreversible spinal damage and by reversible spinal inflammation . Spinal mobility impairment is more influenced by spinal inflammation in early disease , and by structural damage in later disease Objectives : To evaluate the efficacy and drug survival of anti-tumour necrosis factor ( anti-TNF ) therapy in non-radiographic axial spondyloarthritis ( nr-axSpA ) patients treated in clinical practice in Southern Sweden . Method : In this cohort study we prospect ively included 112 patients with nr-axSpA and high disease activity as well as inadequate response or intolerance to non-steroidal anti-inflammatory drugs ( NSAIDs ) receiving their first course of anti-TNF therapy . Patients fulfilling modified New York criteria for ankylosing spondylitis ( AS ) were excluded . The Assessment of SpondyloArthritis International Society ( ASAS ) criteria for axial SpA were fulfilled by 77 % ( n = 86 ) of the included patients . Results : At baseline , the median age of the cohort was 38 years , 59 % were males , 79 % of the patients had imaging suggestive of sacroiliitis ( primarily inflammation on magnetic resonance imaging , MRI ) , 71 % were HLA-B27 positive , and the median disease duration was 6 years and 10 months . At 6 months of follow-up , the median Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) decreased from 5.6 to 3.2 ( p = 0.002 ) , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) decreased from 3.9 to 1.8 ( p = 0.005 ) , and C-reactive protein ( CRP ) level decreased from 4.4 to 1.7 mg/L ( p = 0.001 ) . After 1 year of treatment the Kaplan – Meier estimated drug survival was 76 % , and at 2 years of follow-up this value decreased to 65 % . Patients with inflammatory MRI findings at baseline had significantly better drug survival [ hazard ratio ( HR ) 0.24 , 95 % confidence interval ( CI ) 0.10–0.55 , p = 0.001 ] . Male sex was also associated with higher drug survival ( HR 0.45 , 95 % CI 0.24–0.85 , p = 0.011 ) . CRP level at baseline was not associated with drug survival . Conclusions : Anti-TNF treatment of patients with nr-axSpA in clinical practice result ed in reduced BASDAI and BASFI scores and good drug survival . The results from this study suggest that male gender and positive imaging at baseline are associated with a favourable treatment course OBJECTIVE To examine whether clinical benefits observed after treatment with infliximab were accompanied by improvement in productivity and reduction in time lost from work in a r and omized , double-blind , placebo-controlled , multicenter trial of patients with ankylosing spondylitis ( AS ) . METHODS Adults with active AS receiving st and ard antiinflammatory treatment were r and omly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0 , 2 , 6 , and every 6 weeks thereafter through week 24 . Physical function was measured using the Bath Ankylosing Spondylitis Functional Index . The impact of disease on productivity was measured using a visual analog scale ( range 0 - 10 ) . Self-reported employment status and time lost at work before and during the trial were collected . Spearman 's correlation coefficient was used to examine factors associated with productivity . RESULTS Patients treated with infliximab had a more significant reduction in limitations of work and daily activity due to physical or emotional problems than patients treated with placebo . Of the subset of patients employed full time , patients in the infliximab group had a significantly greater improvement in productivity as early as week 6 compared with the placebo group . The median change from baseline in the productivity score at week 24 was 0.7 ( median percent change 11 % ) in the placebo group compared with 2.1 ( 62 % ) in the infliximab group ( P < 0.05 ) . Daily productivity was significantly correlated with physical function and disease activity at baseline and week 24 . CONCLUSION The daily productivity of patients with active AS was significantly associated with functional impairment and disease activity .  Infliximab treatment significantly improved productivity and reduced workday loss among employed patients with AS OBJECTIVE To evaluate the efficacy and safety of the tumor necrosis factor ( TNF ) antagonist adalimumab in patients with axial spondylarthritis ( SpA ) without radiographically defined sacroiliitis refractory to conventional treatment . METHODS Patients with active axial SpA ( n = 46 ) were r and omized to receive placebo or adalimumab at a dosage of 40 mg subcutaneously every other week for 12 weeks , followed by an open-label extension that continued up to week 52 . The diagnosis of axial SpA required the presence of 3 of 6 diagnostic criteria , including 2 of the following 3 criteria : inflammatory back pain , HLA-B27 positivity , or acute inflammation of the spine or sacroiliac joints on magnetic resonance imaging , in the absence of radiographic evidence of sacroiliitis . The primary end point was a 40 % response according to the improvement criteria of the Assessment of SpondyloArthritis international Society ( ASAS40 ) . RESULTS All 46 patients ( 22 receiving adalimumab and 24 receiving placebo ) completed the 12-week trial ; 38 patients completed the extension period to week 52 . At week 12 , an ASAS40 response was achieved by 54.5 % of the adalimumab-treated patients , as compared with 12.5 % of the placebo-treated patients ( P = 0.004 ) . After switching to adalimumab , a similar degree of efficacy was also achieved by the patients who were initially treated with placebo . Efficacy was maintained in all patients until week 52 . Young age at study entry and an elevated C-reactive protein concentration were the best predictors of achieving an ASAS40 response . Serious adverse events occurred in 5 patients , none of which was related to the study drug . CONCLUSION Adalimumab is the first TNF antagonist to demonstrate good clinical efficacy and safety in patients with axial SpA without radiographically defined sacroiliitis Objective : To estimate the cost‐effectiveness of treating ankylosing spondylitis ( AS ) with infliximab ( Remicade ® ) in Spain for up to 40 years . Methods : A previously published disease model was adapted to the Spanish setting using re source consumption from a cross‐sectional burden of an illness study in 601 patients in Spain .  Cost‐effectiveness estimates were based on a placebo‐controlled clinical trial as well as an open clinical study in Spain . In the model , patients with insufficient response to treatment at 12 weeks [ Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) < 4 or ⩾50 % reduction ] discontinue treatment . The results are presented in 2005 euros , from societal and health‐care payer perspectives . Results : In the societal perspective , infliximab treatment dominates st and ard treatment in both analyses . In the perspective of the health‐care system , with the assumption that , over the long term , functional ability of patients on treatment would decline at half the natural rate , the cost per quality ‐adjusted life year ( QALY ) gained was estimated at EUR 22 519 ( double‐blind trial ) and EUR 8866 ( open study ) . Assuming that patients ’ function on treatment remains stable , the cost‐effectiveness ratios are EUR 15 157 and EUR 5307 , respectively . Under the most conservative assumption ( no effect of treatment on progression ) , the ratios are EUR 31 721 and EUR 13 659 , respectively . In addition , the results are sensitive to the time horizon and discontinuation rates . Conclusions : Our results indicate that infliximab  therapy  for  patients with active AS  should be cost‐effective both in the societal perspective ( dominating ) and in the perspective of the health‐care system ( ranges from EUR 5300 to EUR 32 000 per QALY ) in Spain Objectives To use prospect ively registered data from the Danish nationwide rheumatological data base ( DANBIO ) to describe disease activity , clinical response , treatment duration and predictors of drug survival ( ie , number of days individual patients maintained treatment ) and clinical response among patients with ankylosing spondylitis ( AS ) receiving their first treatment series with a tumour necrosis factor α ( TNFα ) inhibitor .  Methods 842 TNFα inhibitor naive patients with AS were identified in DANBIO .  Clinical response , drug survival and predictors thereof were investigated . ‘ Clinical response ’ was defined as a 50 % or 20 mm reduction in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) within 6 months compared with baseline . Achievement of a BASDAI < 40 mm within 6 months was used as a second response parameter . Results 603 patients ( 72 % ) were men , disease duration 5 ( 1–13 ) years ( median ( IQR ) , age 41 ( 32–50 ) years . 445 ( 53 % ) received infliximab , 247 ( 29 % ) adalimumab and 150 ( 18 % ) etanercept . Parameters at baseline/1-year follow-up were : C-reactive protein ( CRP ) : 14 (7–27)/5 ( 2–10 ) mg/l , BASDAI 59 (44–72)/21 ( 8–39 ) mm , Bath Ankylosing Spondylitis Functional Index ( BASFI ) 50 (34–67)/24 ( 9–45 ) mm , Bath Ankylosing Spondylitis Metrology Index 40 (20–50)/20 ( 10–40 ) mm . Within 6 months , 407/644 patients ( 63 % ) achieved a clinical response . Median drug survival was 4.3 years . One- and 2-year survival rates were 74 % and 63 % , respectively . Baseline characteristics associated with longer drug survival were male gender , CRP > 14 mg/l and low visual analogue scale fatigue ( Cox regression analysis ) . Age , TNFα inhibitor and methotrexate use were insignificant . CRP > 14 mg/l , lower BASFI and younger age at baseline was associated with clinical response and achievement of a BASDAI < 40 mm ( logistic regression analysis ) . Conclusion TNFα inhibitors provide a rapid and sustained decrease of disease activity among patients with AS in clinical practice . Factors associated with continued treatment , clinical response and achievement of a BASDAI < 40 mm were identified OBJECTIVE To evaluate the effect of infliximab on progression of structural damage over 2 years in patients with ankylosing spondylitis ( AS ) . METHODS In the Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy ( ASSERT ) , a r and omized , double-blind , placebo-controlled trial of the efficacy of infliximab compared with placebo , 279 patients with active AS received either placebo through week 24 and then infliximab 5 mg/kg from week 24 through week 96 ( n=78 ) or infliximab 5 mg/kg from baseline through week 96 , administered every 6 weeks after a loading dose ( n=201 ; these patients were the focus of the radiographic analyses ) . Radiographic findings  in patients from the ASSERT trial were indistinguishable from those in a historical control cohort of patients who had no prior use of anti-tumor necrosis factor agents ( from the Outcome in Ankylosing Spondylitis International Study [ OASIS ] data base ; n=192 ) . Radiographic progression of structural damage from baseline to the 2-year followup was scored using the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . All images were scored in one batch . RESULTS Median changes in the mSASSS from baseline to year 2 were 0.0 for both the OASIS and the ASSERT cohorts ( P=0.541 ) . Mean changes in the mSASSS were also similar between the OASIS and ASSERT cohorts ( mean+/-SD change over 2 years 1.0+/-3.2 and 0.9+/-2.6 , respectively ) . In addition , results from sensitivity analyses did not show a statistically significant difference in the mSASSS between the OASIS and ASSERT cohorts . CONCLUSION AS patients who received infliximab from baseline through week 96 did not show a statistically significant difference in inhibition of structural damage progression at year 2 , as assessed using the mSASSS scoring system , when compared with radiographic data from the historical control OASIS cohort . Improvements in clinical outcomes and spinal inflammation have been previously demonstrated with the use of infliximab therapy OBJECTIVES The objective of this study was to assess the humanistic impact of ankylosing spondylitis ( AS ) , and compare the effect of etanercept 50 mg once-weekly ( QW ) , etanercept 25 mg twice-weekly ( BIW ) and placebo on patient-reported outcomes ( PROs ) . METHODS In a 12-week , double-blind , placebo-controlled multicenter study , 356 patients with active AS received etanercept 50 mg QW , etanercept 25 mg BIW or placebo  ( 3:3:1 r and omization , respectively ) . PROs were assessed using Bath Ankylosing Spondylitis Functional Index , Bath Ankylosing Spondylitis Activity Index fatigue item , EuroQOL-5D ( EQ-5D ) utility , EQ-5D visual analog scale and the Medical Outcomes Short Form Question naire ( SF-36 ) scores at baseline and at regular intervals . Mean changes from baseline in PROs were analysed using analysis of covariance to assess differences between etanercept and placebo , or between the two etanercept groups . RESULTS Consistent with earlier reports , AS was associated with quality of life ( QOL ) impairment and functional limitations , similar to or worse than cancer , congestive heart failure , diabetes or depression . Treatment with etanercept 50 mg QW or 25 mg BIW significantly improved QOL and functional status compared with placebo . High proportions of patients achieved clinical ly meaningful improvements in all PRO measures , including physical function , fatigue , pain , psychosocial domains and general health status . Improvements were similar with the two etanercept dose regimens . CONCLUSIONS The more convenient etanercept 50 mg QW dose regimen significantly improves function and QOL in patients with AS , similarly to the st and ard dosing of 25 mg BIW , supporting its use for AS therapy Background and objectives Efficacy of adalimumab for ankylosing spondylitis ( AS ) has been established for Western population s but not in the Chinese population . This study is the first to evaluate the efficacy and safety of adalimumab in Chinese patients with AS . Methods Chinese adults with active AS who had an inadequate response or were intolerant to ≥1 non-steroidal anti-inflammatory drugs were r and omised to  adalimumab 40 mg ( N=229 )  or matching placebo ( N=115 ) subcutaneously every other week ( EOW ) for 12 weeks , followed by a 12-week open-label adalimumab 40 mg EOW phase . The primary efficacy endpoint was the percentage of patients meeting the Assessment in Spondyloarthritis International Society ( ASAS20 ) response criteria at week 12 . The recently developed AS Disease Activity Score ( ASDAS ) , as well as efficacy measures of spinal mobility , disease activity , physical function and quality of life were evaluated . Results At week 12 , adalimumab treatment result ed in a significantly greater percentage of ASAS20 responders than placebo ( 67.2 % versus 30.4 % , respectively ; p<0.001 ) . Differences in ASAS20 were observed as early as week 2 ( 42.8 % vs 6.1 % , respectively ; p<0.001 ) . The percentages of patients achieving ASAS40 , ASAS 5/6 and ASDAS inactive disease were significantly greater with adalimumab than placebo at week 12 ( all p<0.001 ) . Tuberculosis was reported in one patient . No cases of malignancy , lymphoma , demyelinating disease or lupus-like syndrome were reported during the study . Conclusions Adalimumab significantly reduced the signs and symptoms , improved physical function and quality of life of Chinese patients with active AS , and was generally safe and well tolerated in this population OBJECTIVE To obtain results of the second year extension of an original 3 month r and omised , placebo controlled trial ( and the 1 year extension study ) assessing the use of infliximab , a monoclonal antibody to tumour necrosis factor alpha , for the treatment of patients with ankylosing spondylitis ( AS ) . METHODS Of the 54 patients with AS who completed the first year of the study , 52 continued to receive infliximab 5 mg/kg every 6 weeks up to week 102 . The primary end point was the proportion of patients achieving at least 50 % improvement from baseline in the Bath AS Disease Activity Index ( BASDAI ) at week 102 . Other assessment s included patient and physician global assessment s , quality of life as assessed by Short Form-36 , Bath AS Functional Index , Bath AS Metrology Index , and C reactive protein ( CRP ) . RESULTS Improvement in signs and symptoms of AS seen during the first year of the study was sustained during the second year . Forty nine patients ( 71 % of 69 enrolled patients and 49/52 ( 94 % ) patients who started year 2 ) completed the study up to week 102 . Thirty ( 58 % ) patients achieved at least 50 % improvement from baseline in the BASDAI score at week 102 . Scores for other efficacy assessment s were similar at weeks 54 and 102 . Median CRP levels remained low at weeks 54 and 102 ( 3.9 and 4.3 mg/l , respectively ) . Side effects during the second year of the study were similar to those of the first year of treatment with infliximab . CONCLUSIONS Patients with AS treated for 2 years with infliximab 5 mg/kg exhibited a good and durable clinical response OBJECTIVES Many AS patients report periods of perceived higher disease activity ( flares ) . This pilot study aims to document disease activity patterns reported by AS patients and examine associations with disease-specific health status measures . METHODS Consecutive AS patients ( n = 114 ) were asked whether they experience flares , and if they experience symptoms of AS between flares . They were shown the Flare Illustration of disease patterns over time and asked to select the pattern that best described their disease ( i ) since symptom onset and ( ii ) in the past year . Associations between reported disease pattern and disease activity ( Bath AS Disease Activity Index , BASDAI ) ; functional impairment ( Bath AS Functional Index , BASFI ) ; AS Quality of Life ( ASQoL ) ; Back Pain ( Nocturnal and Overall ) and demographic features were assessed in a sub sample ( n = 83 ) ( statistical significance defined at P < or= 0.05 ) . RESULTS Since disease onset 108/113 patients ( 96 % ) reported flares , and 82/99 ( 83 % ) reported symptoms of AS between flares . Flares typically lasted days or weeks . When patients were asked to characterize their disease pattern using the Flare Illustration , patterns with constant symptoms predominated ( > 70 % of patients ) and patterns with constant symptoms since onset ( vs intermittent symptoms ) were associated with worse health status ( ASQoL : P = 0.007 ; BASDAI : P = 0.029 ; BASFI : P = 0.013 , overall back pain : P = 0.025 ) . CONCLUSIONS Almost all AS patients report flares in disease activity : 70 - 80 % report constant symptoms with single/repeated flares , while 20 - 30 % report flares with no intermittent symptoms . The former is associated with a significantly poorer health status . These findings will be vali date d in a prospect i ve study OBJECTIVE To evaluate the cost effectiveness and cost utility of a 3-week course of combined spa therapy and exercise therapy in addition to st and ard treatment consisting of antiinflammatory drugs and weekly group physical therapy in ankylosing spondylitis ( AS ) patients . METHODS A total of 120 Dutch out patients with AS were r and omly allocated into 3 groups of 40 patients each . Group 1 was treated in a  spa resort in Bad Hofgastein , Austria ; group 2 in a spa resort in Arcen , The Netherl and s. The control group stayed at home and continued their usual activities and st and ard treatment during the intervention weeks . After the intervention , all patients followed weekly group physical therapy . The total study period was 40 weeks . Effectiveness of the intervention was assessed by functional ability using the Bath Ankylosing Spondylitis Function Index ( BASFI ) . Utilities were measured with the EuroQoL ( EQ-5D(utility ) ) . A time-integrated summary score defined the clinical effects ( BASFI-area under the curve [ AUC ] ) and utilities ( EQ-5D(utility)-AUC ) over time . Both direct ( health care and non-health care ) and indirect costs were included . Re source utilization and absence from work were registered weekly by the patients in a diary . All costs were calculated from a societal perspective . RESULTS A total of 111 patients completed the diary . The between-group difference for the BASFI-AUC was 1.0 ( 95 % confidence interval [ 95 % CI ] 0.4 - 1.6 ; P = 0.001 ) for group 1 versus controls , and 0.6 ( 95 % CI 0.1 - 1.1 ; P = 0.020 ) for group 2 versus controls . The between-group difference for EQ-5D(utility)-AUC was 0.17 ( 95 % CI 0.09 - 0.25 ; P < 0.001 ) for group 1 versus controls , and 0.08 ( 95 % CI 0.00 - 0.15 ; P = 0.04 ) for group 2 versus controls . The mean total costs per patient ( including costs for spa therapy ) in Euros ( euro ; ) during the study period were euro;3,023 for group 1 , euro;3,240 for group 2 , and euro;1,754 for the control group . The incremental cost-effectiveness ratio per unit effect gained in functional ability ( 0 - 10 scale ) was euro;1,269 ( 95 % CI 497 - 3,316 ) for group 1 , and euro;2,477 ( 95 % CI 601 - 12,098 ) for group 2 . The costs per quality -adjusted life year gained were euro;7,465 ( 95 % CI 3,294 - 14,686 ) for group 1 , and euro;18,575 ( 95 % CI 3,678 - 114,257 ) for group 2 . CONCLUSION Combined spa-exercise therapy besides st and ard treatment with drugs and weekly group physical therapy is more effective and shows favorable cost-effectiveness and cost-utility ratios compared with st and ard treatment alone in patients with AS Background The onset of disease in ankylosing spondylitis ( AS ) is generally earlier than in other joint diseases , exposing patients to a prolonged burden of disease . Whether this is associated with excess mortality is still uncertain . Radiation therapy for AS has previously been shown to increase mortality . The present study investigated st and ardised mortality ratios , causes of death and survival predictors in a large regional cohort of patients with AS . Method A total of 677 patients with AS followed at our hospital since 1977 were matched by gender , age and postal area to three controls from the general population and st and ardised mortality rates ( SMRs ) were calculated . Cause of death was established using patients ' hospital records . In a subset of 360 patients , clinical and demographic data collected during an earlier research visit ( 1998–2000 ) were used in a prospect i ve multivariate analysis of predictors for mortality in AS . Results The crude mortality among patients with AS in this study was 14.5 % ( 98 patients ) ; SMR was only significantly increased among male patients compared with female patients ( 1.63 vs 1.38 , p<0.001 ) . Circulatory disease was the most frequent cause of death ( 40.0 % ) , followed by malignant ( 26.8 % ) and infectious ( 23.2 % ) diseases . Factors independently associated with reduced survival were diagnostic delay ( OR 1.05 ) , increasing levels of C-reactive protein ( OR 2.68 ) , work disability ( OR 3.65 ) and not using any non-steroidal anti-inflammatory drugs ( OR 4.35 ) . Conclusions Mortality is increased in patients with AS and circulatory disease is the most frequent cause of death . Parameters reflecting the duration and intensity of inflammation are associated with reduced survival . These results indicate that , to improve long-term survival in AS , there is a need for early detection and anti-inflammatory treatment as well as a vigilant approach for cardiovascular risk factors OBJECTIVE To evaluate the efficacy of infliximab in HLA-B27-positive patients with magnetic resonance imaging (MRI)-determined early sacroiliitis , using both clinical and MRI assessment s. METHODS Forty patients with recent-onset inflammatory back pain , as assessed by the Calin criteria , HLA-B27 positivity , clinical disease activity as measured by the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , pain and morning stiffness , and magnetic resonance imaging (MRI)-determined sacroiliac joint bone edema were r and omized in a double-blind manner to receive infliximab 5 mg/kg or placebo at 0 , 2 , 6 , and 12 weeks . MRI scans were performed at baseline and 16 weeks and scored by 2 observers ( blinded to both the order of the scans and to treatment group ) , using the Leeds scoring system . Clinical assessment s included the BASDAI , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Ankylosing Spondylitis Quality of Life ( ASQoL ) instrument , the ASsessment in Ankylosing Spondylitis International Working Group criteria ( ASAS ) for improvement , and markers of inflammation . RESULTS The mean reduction in the total MRI score from week 0 to week 16 was significantly greater in infliximab-treated patients compared with placebo-treated patients ( P = 0.033 ) . On average , significantly more lesions resolved in the infliximab group ( P < 0.001 ) , while significantly more new lesions developed in the placebo group ( P = 0.004 ) . Significantly greater improvement in the infliximab group versus the placebo group was also observed for changes from week 0 to week 16 in the BASDAI ( P = 0.002 ) , BASFI ( P = 0.004 ) , and ASQoL ( P = 0.007 ) scores . Responses according to the ASAS criteria for 40 % improvement , the ASAS criteria for 20 % improvement in 5 of 6 domains , and ASAS partial remission were achieved by 61 % , 44 % , and 56 % of infliximab-treated patients , respectively . Infliximab was well tolerated , and no serious adverse events were observed . CONCLUSION Infliximab was an effective therapy for early sacroiliitis , providing a reduction in disease activity by week 16 . This study is the first to show that infliximab is effective for reducing clinical and imaging evidence of disease activity in patients with MRI-determined early axial spondylarthritis 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 Objective . To analyze the longterm followup of a series of Brazilian patients with undifferentiated spondyloarthritis ( uSpA ) . Methods . Prospect i ve study analyzing a group of 111 patients with the diagnosis of uSpA , fulfilling the European Spondylarthropathy Study Group and the Amor criteria , who were followed for 5 to 10 years in a single university referral center . Patients had their outcome analyzed at 5 , 7 , and 10 years . Results . There was a predominance of men ( 81.1 % ) , white ethnicity ( 78.4 % ) , and positive HLA-B27 ( 61.3 % ) , with a mean age at onset of 27.2 years . Twenty-seven patients presented development to ankylosing spondylitis ( AS ; 24.3 % ) and 3 to psoriatic arthritis ( PsA ; 2.7 % ) , while 25 patients ( 22.5 % ) went into remission during the followup . Univariate logistic regression analysis revealed that ethnicity , HLA-B27 , buttock pain , inflammatory low back pain , ankle involvement , grade I sacroiliitis at the beginning of the study , and the use of sulfasalazine were statistically associated with progression to AS . Multivariate logistic regression analysis revealed that HLA-B27 ( p = 0.035 , OR 6.720 , 95 % CI 11.45–39.43 ) and buttock pain ( p = 0.009 , OR 6.211 , 95 % CI 1.591–24.25 ) were statistically associated with progression to AS . Conclusion . In a longterm followup of 111 Brazilian patients with uSpA , HLA-B27 and buttock pain were significant predictors of progression to a definite disease OBJECTIVES In the past , treatment options for ankylosing spondylitis ( AS ) have been limited , and the introduction of new treatments such as infliximab will have a noticeable impact on health-care budgets . The objective of this study was therefore to assess the current burden of the disease and estimate the cost-effectiveness of infliximab treatments . METHODS A cross-sectional retrospective observational study of re source consumption and utility related to disease severity was performed in patients who had participated in a population survey between 1992 and 1994 at the University of Bath and patients regularly followed at the Royal National Hospital for Rheumatic Diseases in Bath for up to 9 years .  Mean costs and utility were estimated using a regression model including age , gender , disease duration , disease activity and functional status , and disease development was expressed as annual progression of functional disability . Cost-effectiveness of infliximab was modelled using a 3-month placebo-controlled clinical trial with open 1-yr extension in 70 patients , over a total time frame of 2 yr . In the model , costs and utility controlled for disease severity and age from the observational study were assigned to individual patients . The effect of long-term treatment was evaluated in a hypothetical model over 30 yr . RESULTS Fifty-seven per cent of patients answered the question naires . The mean age was 57 ( s.d . 11.2 ) yr , 74 % were male and mean disease duration was 30.2 ( 11.7 ) yr .  Mean total costs were estimated at pound 6765 ( s.d . pound 166 ) . Indirect costs represented 57.9 % and non-medical costs such as investments and informal care accounted for 16.5 % of total costs . Mean utility was 0.67 ( 0.21 ) . In the main model , mean costs for untreated patients are estimated at pound 25,128 . For the infliximab group , mean costs ( excluding treatment ) are estimated at pound 17,240 , a reduction of 31 % . Thus , part of the treatment cost was offset by savings in other re sources ( pound 7888 ) , leaving an incremental cost of pound 6214 . Treatment increased the number of quality -adjusted live years ( QALYs ) by 0.175 QALYs , leading to a cost per QALY gained of pound 35,400 for the first year of treatment . When treatment is assumed to continue for the full 2 yr , the cost per QALY is pound 32,800 . When infliximab infusions are given every 8 weeks instead of every 6 weeks , the cost per QALY is reduced to pound 17,300 . In the long-term model , the cost per QALY is estimated at pound 9600 . CONCLUSIONS Non-medical costs and production losses dominate costs in AS , and economic evaluation must therefore adopt a societal perspective . The cost of treatment with infliximab is partly offset by reductions in the cost of the disease and patients ' quality of life is increased , leading to a cost per QALY gained in the vicinity of pound 30,000 to pound 40,000 in the short term , but potentially below pound 10,000 in the long term OBJECTIVE To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac ( SI ) joint inflammation , by magnetic resonance imaging ( MRI ) in patients with active ankylosing spondylitis ( AS ) . METHODS This was a r and omized , multicenter , double-blind , placebo-controlled study . Patients ( n = 82 ) received 40 mg adalimumab or placebo every other week during an initial 24-week double-blind period . MRIs of both the spine and SI joints were obtained at baseline , week 12 , and week 52 . Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada ( SPARCC ) MRI index . RESULTS The spine SPARCC score in placebo-treated patients increased by a mean of 9.4 % from baseline , compared with a mean decrease of 53.6 % in adalimumab-treated patients ( P < 0.001 ) ; the SI joint SPARCC score decreased by a mean of 12.7 % from baseline in placebo-treated patients and by 52.9 % in adalimumab-treated patients ( P = 0.017 ) . The response in adalimumab-treated patients was maintained at week 52 . Placebo-treated patients were switched to open-label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52 . Similar large reductions in the spine and SI joint SPARCC scores were noted , even in patients who failed to meet the ASsessment in Ankylosing Spondylitis ( International Working Group ) criteria ( nonresponders ) at 12 weeks . In adalimumab-treated patients , a reduced C-reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score ( P = 0.018 ) . CONCLUSION Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment , and these improvements were maintained for up to 52 weeks OBJECTIVE To assess prospect ively the rates and to explore predictors of spinal radiographic progression over 2 years in a cohort of patients with early axial spondylarthritis ( SpA ) . METHODS Two hundred ten patients with axial SpA from the German Spondyloarthritis Inception Cohort were selected for this analysis based on the availability of radiographs at baseline and after 2 years of followup . Spinal radiographs were scored by 2 trained readers in a blinded , r and omly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) . Spinal radiographic progression was defined as worsening of the mean mSASSS by ≥2 units over 2 years . RESULTS Among the patients with axial SpA , 14.3 % showed spinal radiographic progression after 2 years ( 20 % of those with AS and 7.4 % of those with nonradiographic axial SpA ) . The following parameters were independently associated with spinal radiographic progression : presence of syndesmophytes at baseline ( odds ratio [ OR ] 6.29 , P < 0.001 ) , elevated levels of markers of systemic inflammation ( for the erythrocyte sedimentation rate , OR 4.04 , P = 0.001 ; for C-reactive protein level time-averaged over 2 years , OR 3.81 , P = 0.001 ) , and cigarette smoking ( OR 2.75 , P = 0.012 ) . These associations were confirmed by multivariate logistic regression analysis . No clear association with spinal radiographic progression was observed for HLA-B27 status , sex , age , disease duration , Bath Ankylosing Spondylitis Disease Activity Index , Bath Ankylosing Spondylitis Functional Index , presence of peripheral arthritis , enthesitis , psoriasis , treatment with nonsteroidal antiinflammatory drugs , or treatment with disease-modifying antirheumatic drugs at baseline . CONCLUSION The presence of radiographic damage at baseline ( syndesmophytes ) , elevated levels of acute-phase reactants , and cigarette smoking were all independently associated with spinal radiographic progression in patients with early axial Purpose : To compare aspects of validity of EuroQol—5 Dimensions ( EQ-5D ) and Short-Form—6 Dimensions ( SF-6D ) , two indirect utility instruments , and the well-being rating scale ( RS ) in ankylosing spondylitis ( AS ) . Methods : EQ-5D , SF-6D and RS were available for 254 patients fulfilling modified New York criteria . 134 patients were part of an observational cohort and 120 were part of a r and omised controlled trial ( RCT ) . Aspects of validity assessed were truth ( agreement and correlation with external health measures ) and discrimination ( differentiation between health states , repeatability and detection of treatment effect ) . Results : Median ( range ) values were 0.69 ( −0.08–1.00 ) for the EQ-5D , 0.65 ( 0.35–0.95 ) for the SF-6D and 0.65 ( 0.14–1.00 ) for the RS . Agreement ( intraclass correlation coefficient ) was moderate ( 0.46–0.55 ) . Instruments correlated equally with disease activity , functioning and quality of life . The SF-6D showed smaller average differences in utility between patients with better and worse disease compared with the EQ-5D and the RS . The smallest detectable difference ( SDD ) ( in the control group of RCT ) was 0.36 , 0.17 and 0.33 for EQ-5D , SF-6D and RS , respectively . The ability to detect treatment effect ( in the intervention trial ) showed st and ardised effect sizes that were moderate for EQ-5D and SF-6D ( 0.63 and 0.64 ) and low for the RS ( 0.23 ) . Conclusion : In patients with AS , EQ-5D , SF-6D and the RS correlate equally well with external measures of health , but have different psychometric properties . The SDD is most favourable for the SF-6D , but it discriminates less well between patients with different disease severities . The RS has a poorer ability to detect treatment effects . It is difficult to recommend one of the instruments Objectives Etanercept has been shown to be rapidly effective in suppressing disease activity in ankylosing spondylitis ( AS ) . The aim of this study was to determine whether etanercept improves work instability as measured by the Ankylosing Spondylitis Work Instability Scale ( AS-WIS ) . Method Forty patients with active AS who were in work but were work unstable were recruited . Patients were r and omised to receive 25 mg etanercept or placebo twice weekly for 12 weeks . The primary outcome was change in AS-WIS at week 12 . The AS-WIS is a patient-derived outcome measure which allows stratification of the risk of job loss . Secondary outcomes included clinical outcomes and gait parameters . Results The mean improvement in AS-WIS score at week 12 was 2.75 in the etanercept group and 0.68 in the placebo group ( p=0.125 ) . The risk of job loss decreased for 11 ( 55 % ) of the etanercept group compared with 7 ( 35 % ) in the placebo group . Conversely , the risk of job loss increased in 3 ( 15 % ) of the placebo group compared with 1 ( 5 % ) in the etanercept group . There was no statistically significant difference between treatment groups in change in WIS categories ( Mann – Whitney U test=0.153 , p=0.160 ) . Significant improvement with etanercept was seen at week 12 in clinical outcomes and gait parameters .  Etanercept was well tolerated , with no dropouts due to adverse events . Conclusion This small study confirms the efficacy of etanercept on clinical outcome measures in patients with AS and suggests an effect on work instability which needs to be replicated in a larger controlled study
BACKGROUND Tumour necrosis factor (TNF)-α inhibitors ( anti-TNFs ) are typically used when the inflammatory rheumatologic diseases ankylosing spondylitis ( AS ) and non-radiographic axial spondyloarthritis ( nr-AxSpA ) have not responded adequately to conventional therapy .
Current National Institute for Health and Care Excellence ( NICE ) guidance recommends treatment with adalimumab , etanercept and golimumab in adults with active ( severe ) AS only if certain criteria are fulfilled but it does not recommend infliximab for AS .
Anti-TNFs for patients with nr-AxSpA have not previously been appraised by NICE .
OBJECTIVE To determine the clinical effectiveness , safety and cost-effectiveness within the NHS of adalimumab , certolizumab pegol , etanercept , golimumab and infliximab , within their licensed indications , for the treatment of severe active AS or severe nr-AxSpA ( but with objective signs of inflammation ) .