[Pirprofen, indomethacin and placebo in ankylosing spondylitis. Double-blind comparison]. Evaluation of the Quality of Prognosis Studies in Systematic Reviews Efficacy of cyclo-oxygenase-2 inhibition by etoricoxib and naproxen on the axial manifestations of ankylosing spondylitis in the presence of peripheral arthritis MRI and clinical findings in patients with ankylosing spondylitis eligible for anti-tumour necrosis factor therapy after a short course of etoricoxib Celecoxib is efficacious and well tolerated in treating signs and symptoms of ankylosing spondylitis. Continuous NSAID use reverts the effects of inflammation on radiographic progression in patients with ankylosing spondylitis A 12-week double-blind study of the efficacy, safety and tolerance of pirazolac b.i.d. compared with indomethacin t.i.d. in patients with ankylosing spondylitis. Double-blind trial of naproxen and phenylbutazone in ankylosing spondylitis. Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. A double blind comparison of diclofenac and indomethacin in the treatment of ankylosing spondylitis. Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2 Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. Ankylosing spondylitis: what is the optimum duration of a clinical study? A one year versus a 6 weeks non-steroidal anti-inflammatory drug trial. Proquazone (Biarison) and indomethacin (Indocid) in the treatment of ankylosing spondylitis. Two comparative, clinical, double-blind studies. Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis A comparison of diflunisal and phenylbutazone in the treatment of ankylosing spondylitis [Criteria of the classification of spondylarthropathies]. A comparative study of nabumetone and indomethacin in ankylosing spondylitis. Meclofenamate sodium in the treatment of ankylosing spondylitis. Report of a European double-blind controlled multicenter study. The development of Assessment of SpondyloArthritis international Society classification criteria for axial spondyloarthritis (part II): validation and final selection Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. Major reduction in spinal inflammation in patients with ankylosing spondylitis after treatment with infliximab: results of a multicenter, randomized, double-blind, placebo-controlled magnetic resonance imaging study. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison Ankylosing Spondylitis Disease Activity Score (ASDAS): defining cut-off values for disease activity states and improvement scores A comparative study of Butacote and Naprosyn in ankylosing spondylitis. Effects of add-on montelukast on airway hyperresponsiveness in patients with well-controlled asthma – a pilot study Tolfenamic acid in ankylosing spondylarthritis: a double-blind comparison to indomethacin. Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: cohort study Flurbiprofen in the treatment of ankylosing spondylitis. A comparison with phenylbutazone. The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. A double-blind cross-over trial of fenoprofen and phenylbutazone in ankylosing spondylitis. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial. Double-blind Cross-over Trial of Flurbiprofen and Phenylbutazone in Ankylosing Spondylitis Undifferentiated Spondyloarthropathies: A 2-Year Follow-up Study Nonsteroidal antiinflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Tenoxicam compared with diclofenac in patients with ankylosing spondylitis. Oxaprozin versus Diclofenac Sodium in the Treatment of Ankylosing Spondylitis A comparison of indoprofen and indomethacin in the treatment of ankylosing spondylitis. A controlled comparative trial of Butacote and fenclofenac in the treatment of ankylosing spondylitis. Ximoprofen in ankylosing spondylitis. A double blind placebo controlled dose ranging study. Evaluation of the efficacy of etoricoxib in ankylosing spondylitis: results of a fifty-two-week, randomized, controlled study. [Azapropazone versus indomethacin in a double blind test with patients with ankylosing spondylitis]. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Sulindac in ankylosing spondylitis. Double-blind evaluation of sulindac and indomethacin. Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug. Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis Double-blind cross-over comparison of indomethacin, flurbiprofen, and placebo in ankylosing spondylitis. ASDAS, a highly discriminatory ASAS-endorsed disease activity score in patients with ankylosing spondylitis Treatment of ankylosing spondylitis with flurbiprofen and indomethacin. [A double blind comparison of naproxen and indomethacin on the after-midnight-pain of patients with morbus bechterew]. Isoxicam vs ketoprofen in ankylosing spondylitis. Comparison of two different dosages of celecoxib with diclofenac for the treatment of active ankylosing spondylitis: results of a 12-week randomised, double-blind, controlled study. A comparative study of benoxaprofen and indomethacin in ankylosing spondylitis. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Treatment of ankylosing spondylitis with flurbiprofen or phenylbutazone Development and preselection of criteria for short term improvement after anti-TNF alpha treatment in ankylosing spondylitis. Ankylosing spondylitis assessment group preliminary definition of short-term improvement in ankylosing spondylitis. [Ankylosing spondylitis. Comparative trial of two non-steroidal anti-inflammatory agents: pirprofen and ketoprofen]. [Clinical results of a multicentral double-blind examination of naproxen compared to indomethacin in chronic rheumatoid arthritis, ankylosing spondylitis, and osteoarthrosis]. A comparison of flurbiprofen with naproxen in ankylosing spondylitis. Evaluation of indomethacin by a controlled, cross-over technique in 30 patients with ankylosing spondylitis. A parallel group comparison of tenoxicam and piroxicam in patients with ankylosing spondylitis. Morning stiffness and nightime pain in ankylosing spondylitis. A comparison between enteric-coated and plain naproxen tablets. Flurbiprofen in the treatment of ankylosing spondylitis. A comparison with indomethacin. Tolerability and efficacy of a slow-release indomethacin tablet in ankylosing spondylitis. Nonsteroidal anti-inflammatory agents in rheumatoid arthritis and ankylosing spondylitis. The efficacy and tolerability of aceclofenac in the treatment of patients with ankylosing spondylitis: a multicenter controlled clinical trial. Aceclofenac Indomethacin Study Group. A comparative study of benoxaprofen and ketoprofen in ankylosing spondylitis. Double-blind study of ketoprofen and phenylbutazone in ankylosing spondylitis. A trial of feprazone in ankylosing spondylitis. Early detection of sacroiliitis on magnetic resonance imaging and subsequent development of sacroiliitis on plain radiography. A prospective, longitudinal study. Spondylitic disease without radiologic evidence of sacroiliitis in relatives of HLA-B27 positive ankylosing spondylitis patients. Celecoxib versus omeprazole and diclofenac in patients with osteoarthritis and rheumatoid arthritis (CONDOR): a randomised trial Effect of non-steroidal anti-inflammatory drugs on radiographic spinal progression in patients with axial spondyloarthritis: results from the German Spondyloarthritis Inception Cohort
One hundred and four patients with ankylosing spondylitis were involved in a comparative trial carried out in one single centre . They were given either pirprofene ( 1000 mg/day ) , indomethacin ( 125 mg/day ) or a placebo for 6 consecutive weeks . Response to treatment was assessed after 1 , 2 , 4 and 6 weeks on the basis of 4 subjective criteria and 6 st and ard measurements . The overall therapeutic results were judged by the investigator to be satisfactory in 87 % of patients in the pirprofene group , 77 % in the indomethacin group and 29 % in the placebo group ( p less than 0.01 ) . A large number of patients in each group ( including 34 % on placebo ) reported side effects . Treatment was discontinued on account of gastric pain in two patients ( one on pirprofen , the other on indomethacin ) . No abnormalities were detected in laboratory tests Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items Objective : The combined efficacy of selective and non-selective cyclo-oxygenase-2 ( COX-2 ) inhibition on the axial manifestations of ankylosing spondylitis ( AS ) in the presence or absence of chronic peripheral arthritis was evaluated . Methods : In a post hoc subgroup analysis of a 6 week , r and omised , double blind , placebo controlled trial , 387 patients with active axial AS were r and omised to receive etoricoxib 90 mg or 120 mg once a day , naproxen 500 mg twice daily , or placebo . R and omisation was stratified by the presence or absence of chronic peripheral arthritis . The primary outcome measure was the time weighted average change from baseline of spine pain intensity . Efficacy data from the three groups receiving active treatment ( the NSAID/COX-2 inhibitor group ) were combined to improve precision . An analysis of covariance model was used to evaluate the effect of peripheral disease on treatment response . Results : 93 patients were allocated to receive placebo and 294 to active treatment ( naproxen or etoricoxib ) . The combined NSAID/COX-2 inhibitor group had a significant treatment response compared with the placebo group for all efficacy measures , both in patients with and without peripheral arthritis . A significantly greater difference in mean patient assessment of spine pain was found between active and placebo treatments in patients without compared with those with peripheral arthritis ( p = 0.005 ; −32.5 mm v −17.0 mm , respectively ) . Similar differences , although not statistically significant , were seen for other end points . Conclusion : NSAIDs and COX-2 inhibitors have a clinical ly relevant symptomatic effect on axial AS irrespective of the presence of peripheral arthritis . In this exploratory analysis spinal improvement appeared to be greater in patients without peripheral disease Objective : To describe and assess the response to short-term etoricoxib as shown by MRI and clinical variables in patients with ankylosing spondylitis ( AS ) selected for eligibility for anti-tumour necrosis factor therapy .  Methods : In a 6-week open-label study , 22 patients with AS and eligible for biological therapy were treated with 90 mg of etoricoxib daily . Clinical and laboratory parameters were obtained and MRI of the sacroiliac joints and the lower thoracic and lumbar spine performed at baseline and at week 6 . The primary end point was the proportion of patients fulfilling the SpondyloArthritis international Society ( ASAS ) response criteria for biological therapies ( ASASBIO ) while secondary end points included the change in MRI-determined bone lesions . Results : Eight of 20 completers improved enough to meet the ASASBIO response criteria and most clinical variables improved significantly . Fifteen patients had a total of 63 MRI-detectable lesions ; overall , 13/60 lesions with paired scans either resolved completely or improved , while five lesions worsened or appeared during treatment . Conclusion : Etoricoxib is an effective symptomatic treatment for patients with AS ; however , its effect on MRI-detected lesions is small . Further studies are needed to determine the effect of etoricoxib on MRI-determined bone oedema OBJECTIVE To evaluate the efficacy and safety of celecoxib in patients with ankylosing spondylitis ( AS ) . METHODS This was a 12-week r and omized , double-blind , placebo-controlled study with 4 treatment arms : celecoxib 200 mg qd , celecoxib 400 mg qd , naproxen 500 mg bid , and placebo .  Patients ( age 18 - 75 yrs ) requiring daily treatment with nonselective nonsteroidal antiinflammatory drugs , and with a pain intensity on visual analog scale ( VAS ) > or = 50 mm worsening by 30 % compared with a pre inclusion visit ( 14 days prior ) were studied . Primary endpoints were least-squares mean changes from baseline in pain intensity , disease activity ( patient global assessment VAS ) , and functional impairment [ Bath Ankylosing Spondylitis Functional Index ( BASFI ) ] . Adverse events were monitored throughout the study . RESULTS Of 611 r and omized patients , 137 were allocated to celecoxib 200 mg , 161 to celecoxib 400 mg , 157 to naproxen , and 156 to placebo . Improvements in least-squares mean pain intensity , disease activity , and BASFI scores were significantly greater in the celecoxib 200 mg , celecoxib 400 mg , and naproxen groups than in the placebo group ( p < or = 0.001 ) at Week 12 and the interim timepoints , Weeks 1 , 3 , and 6 . Celecoxib 400 mg was as effective as naproxen ; however , naproxen was more effective than celecoxib 200 mg . Celecoxib was well tolerated , with an adverse event profile similar to placebo . However , 3 naproxen-treated patients experienced serious treatment-related gastrointestinal ( GI ) adverse events ( one severe gastric ulcer , one moderate GI hemorrhage , one severe GI hemorrhage ) . CONCLUSION In this 12-week study , celecoxib 200 mg qd and 400 mg qd were efficacious and well tolerated in treating signs and symptoms of AS Objectives The aim was to compare continuous and on-dem and NSAID treatment with respect to their ability to suppress radiographic progression in subgroups of patients with high/elevated CRP-levels , ESR , ASDAS-levels or BASDAI-levels in comparison to patients with normal levels . Methods Post-hoc analyses were performed in a r and omized trial comparing continuous and on-dem and NSAID treatment . Relevant high/elevated subgroups were created based on time-averaged ( ta ) CRP ( > 5mg/L ) , ta-ESR ( > 12mm/hr ) , ta-BASDAI ( > 4 ) , ta-ASDAS-CRP ( > 2.1 ) and ta-ASDAS-ESR ( > 2.1 ) . Subgroups were further split according to NSAID-use ( continuous vs. on-dem and ) . Radiological progression was presented in probability plots . Statistical interactions were tested using multiple and logistic regression analysis . Differences in radiological progression were analysed using the Chi-square and Mann-Whitney U test . Results 150 participants r and omized to either the continuous-treatment group ( n=76 ) , or the on-dem and group ( n=74 ) had complete radiographs and were included . The effect of slowing radiological progression with continuous NSAID therapy was more pronounced in patients with elevated ta-CRP-levels , elevated ta-ESR , high ta-ASDAS-CRP or high ta-ASDAS-ESR versus patients with low/normal values . No such effect was found for participants with high vs. low BASDAI . Also , in participants with elevated ta-ESR ( irrespective of treatment ) , there appeared to be a higher rate of structural progression than in participants with normal ta-ESR . Regression analyses showed that continuous NSAID treatment neutralizes the negative effect of inflammation ( high ta-ESR ) . Conclusions Patients with elevated acute phase reactants seem to benefit most from continuous treatment with NSAIDs . Continuous NSAID-therapy in patients with elevated acute phase reactants may lead to an improved benefit-risk-ratio of these drugs A 12-week trial was carried out to compare the efficacy of pirazolac ( 300 - 600 mg b.i.d . ) with that of indomethacin ( 25 - 50 mg t.i.d . ) in patients with ankylosing spondylitis . A total of 119 patients completed the treatment period , with 32 drop-outs . Both therapies showed significant improvements in clinical symptoms In a double-blind double-placebo crossover study naproxen ( 500 - 750 mg daily ) was found to be equivalent to phenylbutazone ( 400 - 600 mg daily ) in the control of disease activity in 20 patients suffering from ankylosing spondylitis during a two times 5-week trial period . No serious side effects were observed during the trial period . Gastric complaints occurred twice as often under phenylbutazone as under naproxen BACKGROUND Selective inhibition of cyclooxygenase-2 ( COX-2 ) may be associated with an increased risk of thrombotic events , but only limited long-term data have been available for analysis . We report on the cardiovascular outcomes associated with the use of the selective COX-2 inhibitor rofecoxib in a long-term , multicenter , r and omized , placebo-controlled , double-blind trial design ed to determine the effect of three years of treatment with rofecoxib on the risk of recurrent neoplastic polyps of the large bowel in patients with a history of colorectal adenomas . METHODS A total of 2586 patients with a history of colorectal adenomas underwent r and omization : 1287 were assigned to receive 25 mg of rofecoxib daily , and 1299 to receive placebo . All investigator-reported serious adverse events that represented potential thrombotic cardiovascular events were adjudicated in a blinded fashion by an external committee . RESULTS A total of 46 patients in the rofecoxib group had a confirmed thrombotic event during 3059 patient-years of follow-up ( 1.50 events per 100 patient-years ) , as compared with 26 patients in the placebo group during 3327 patient-years of follow-up ( 0.78 event per 100 patient-years ) ; the corresponding relative risk was 1.92 ( 95 percent confidence interval , 1.19 to 3.11 ; P=0.008 ) . The increased relative risk became apparent after 18 months of treatment ; during the first 18 months , the event rates were similar in the two groups . The results primarily reflect a greater number of myocardial infa rct ions and ischemic cerebrovascular events in the rofecoxib group . There was earlier separation ( at approximately five months ) between groups in the incidence of nonadjudicated investigator-reported congestive heart failure , pulmonary edema , or cardiac failure ( hazard ratio for the comparison of the rofecoxib group with the placebo group , 4.61 ; 95 percent confidence interval , 1.50 to 18.83 ) . Overall and cardiovascular mortality was similar in the two groups . CONCLUSIONS Among patients with a history of colorectal adenomas , the use of rofecoxib was associated with an increased cardiovascular risk During almost 12 years of development and clinical trials , diclofenac sodium has been shown to be both effective and safe as a new nonsteroidal antiinflammatory drug ( NSAID ) for the treatment of rheumatic diseases including ankylosing spondylitis ( AS ) . We compared the safety and efficacy of 75 , 100 , or 125 mg/day of diclofenac with the same doses of indomethacin in a multicenter , r and omized , parallel group trial in patients with AS . A single blind placebo washout period of 2 days to 2 weeks preceded the 13-week double blind treatment period . Both diclofenac and indomethacin produced significant ( p less than 0.001 ) improvement from baseline for all 14 efficacy variables analyzed . There were no significant between treatment differences . Differences favored diclofenac in the frequency and the severity of adverse experiences reported and in the frequency of complaints affecting the central nervous system Objective To investigate whether biologic-free remission can be achieved in patients with early , active axial spondyloarthritis ( SpA ) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen ( NPX ) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control . Method Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial ( INFAST ) Part 1 was a double-blind , r and omised , controlled trial in biologic-naïve patients with early , active , moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks . Patients achieving Assessment of SpondyloArthritis international Society ( ASAS ) partial remission at week 28 continued to Part 2 and were r and omised ( 1:1 ) to NPX or no treatment until week 52 . Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests . Results At week 52 , similar percentages of patients in the NPX group ( 47.5 % , 19/40 ) and the no-treatment group ( 40.0 % , 16/40 ) maintained partial remission , p=0.65 . Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group ( p=0.38 ) . Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28 , the start of follow-up treatment ( NPX , 0.7 ; no treatment , 0.6 ) , and remained low at week 52 ( NPX , 1.2 ; no treatment , 1.7 ) . Conclusions In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone , disease activity remained low , and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped CONTEXT Conventional nonsteroidal anti-inflammatory drugs ( NSAIDs ) are associated with a spectrum of toxic effects , notably gastrointestinal ( GI ) effects , because of inhibition of cyclooxygenase (COX)-1 . Whether COX-2-specific inhibitors are associated with fewer clinical GI toxic effects is unknown . OBJECTIVE To determine whether celecoxib , a COX-2-specific inhibitor , is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs . DESIGN The Celecoxib Long-term Arthritis Safety Study ( CLASS ) , a double-blind , r and omized controlled trial conducted from September 1998 to March 2000 . SETTING Three hundred eighty-six clinical sites in the United States and Canada . PARTICIPANTS A total of 8059 patients ( > /=18 years old ) with osteoarthritis ( OA ) or rheumatoid arthritis ( RA ) were enrolled in the study , and 7968 received at least 1 dose of study drug . A total of 4573 patients ( 57 % ) received treatment for 6 months . INTERVENTIONS Patients were r and omly assigned to receive celecoxib , 400 mg twice per day ( 2 and 4 times the maximum RA and OA dosages , respectively ; n = 3987 ) ; ibuprofen , 800 mg 3 times per day ( n = 1985 ) ; or diclofenac , 75 mg twice per day ( n = 1996 ) . Aspirin use for cardiovascular prophylaxis ( < /=325 mg/d ) was permitted . MAIN OUTCOME MEASURES Incidence of prospect ively defined symptomatic upper GI ulcers and ulcer complications ( bleeding , perforation , and obstruction ) and other adverse effects during the 6-month treatment period . RESULTS For all patients , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76 % vs 1.45 % ( P = .09 ) and 2 . 08 % vs 3.54 % ( P = .02 ) , respectively . For patients not taking aspirin  , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44 % vs 1.27 % ( P = .04 ) and 1.40 % vs 2.91 % ( P = .02 ) . For patients taking aspirin  , the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01 % vs 2.12 % ( P = .92 ) and 4.70 % vs 6.00 % ( P = .49 ) . Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss , GI intolerance , hepatotoxicity , or renal toxicity . No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs , irrespective of aspirin use . CONCLUSIONS In this study , celecoxib , at dosages greater than those indicated clinical ly , was associated with a lower incidence of symptomatic ulcers and ulcer complications combined , as well as other clinical ly important toxic effects , compared with NSAIDs at st and ard dosages . The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly . JAMA . 2000;284:1247 - OBJECTIVE To consider the relevance of the duration of a clinical trial in ankylosing spondylitis : long-term ( i.e. 1 yr ) vs short-term ( i.e. 6 weeks ) assessment of a non-steroidal anti-inflammatory drug (NSAID)-placebo controlled study . METHODS The design was a prospect i ve , multicentre , double-blind , placebo-controlled study of 6 weeks duration with a 12 months double-blind extension . Study drugs were placebo ( n = 121 ) or active NSAID ( n = 352 ) . A decrease of at least 50 % in pain and /or global assessment and /or functional impairment during the study defined the response to treatment . The percentage of patients discontinuing the study drug over time ( life table analysis ) permitted the evaluation of both the efficacy and toxicity . RESULTS Among the 473 recruited patients , the percentage of responders was similar at 1 yr and week 6 with a highly statistically significant difference in favour of the active NSAID groups when compared to placebo ( at 1 yr , 17 % in the placebo group vs 37 , 50 and 43 % in the piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg , respectively , for the patient 's overall assessment ) without any statistically significant difference between the three active groups . However , evaluation of the patients discontinuing the study drug during the 1 yr of the study permitted the detection of a statistically significant difference between the active NSAID groups . A lower percentage of patients taking meloxicam 22.5 mg had to discontinue the study drug when compared to either meloxicam 15 mg or piroxicam 20 mg ( 37 % vs 53 % and 53 % , respectively , P < 0.05 ) . By 52 weeks , drug-related upper gastrointestinal adverse events occurred in 13 , 32 , 20 and 18 % in the placebo , piroxicam 20 mg , meloxicam 15 mg and meloxicam 22.5 mg groups , respectively . Some of the adverse events occurred only after week 6 . CONCLUSION This study suggests that a 1 yr trial might be of optimum value compared to a 6 week assessment in order to define better the efficacy and tolerability of NSAIDs in ankylosing spondylitis The effect and tolerance of proquazone and indomethacin in patients suffering from ankylosing spondylitis were compared in two separate 3-week clinical , double-blind , r and omized studies on total of 60 patients . In the first study 16 patients were treated with proquazone and 14 patients with indomethacin , and in the second study 15 patients were treated in each group . Both drugs were found to have an evident , equally strong effect on pain and functional capacity in daily doses of 900 mg and 75 mg respectively . Severe side effects were not noted with either one of the drugs . Patients with previously known intolerance to indomethacin were excluded from the studies . Gastronitestinal disturbances seem to be the most commonly appearing side effect in patients treated with proquazone Background Clinical analgesic trials typically report response as group mean results . However , research has shown that few patients are average and most have responses at the extremes . Moreover , group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level . Responder analyses and numbers-needed-to-treat ( NNT ) are considered more relevant for evaluating treatment response . We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) score improvement and the associated NNTs . Methods This was a post-hoc analysis of a 6-week , r and omized , double-blind study ( N = 387 ) comparing etoricoxib 90 mg , etoricoxib 120 mg , naproxen 1000 mg , and placebo in AS . Spine pain and BASDAI were measured on a 100-mm visual analog scale . The number and percentage of patients achieving ≥30 % and ≥50 % improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs . Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation . Results For etoricoxib 90 mg , etoricoxib 120 mg and naproxen 1000 mg , the NNTs at 6 weeks compared with placebo were 2.0 , 2.0 , and 2.7 respectively for BASDAI ≥30 % improvement , and 3.2 , 2.8 , and 4.1 for ≥50 % improvement . For spine pain , the NNTs were 1.9 , 2.0 , and 3.2 , respectively , for ≥30 % improvement , and 2.7 , 2.5 , and 3.7 for ≥50 % improvement . The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinical ly meaningful difference for pain . Response rates and NNTs were generally similar and stable over 2 , 4 , and 6 weeks . Conclusions For every 2 patients treated with etoricoxib , 1 achieved a clinical ly meaningful ( ≥30 % ) improvement in spine pain and BASDAI beyond that expected from placebo , whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen . Use of NNTs and responder analyses provide additional , complementary information beyond population mean responses when assessing efficacy compared to placebo and amongst active therapies Summary A 12-week double-blind r and omized drug trial followed by an open extension period of 36 weeks was carried out in 38 male patients with ankylosing spondylitis ( AS ) to compare the efficacy and safety of diflunisal ( 500 mg twice daily ) and phenylbutazone ( 200 mg twice daily ) . Both drugs proved to be effective in improving the severity of symptoms associated with AS , and this improvement was maintained throughout the open extension period . Initially diflunisal had a more pronounced and rapid analgesic action , whereas phenylbutazone was more effective in increasing axial mobility .  During the study 9 patients dropped out : 3 in each treatment group due to side effects and 1 in each group due to lack of efficacy ;  another patient was lost to follow-up . The two drugs were similarly safe as judged by the occurrence of adverse clinical effects , mainly gastrointestinal . This study again demonstrates the value of phenylbutazone in AS but , taking into account the possible haematological side effects , the use of other NSAIDs is stressed . Diflunisal is an alternative capable of improving the painful stiffness associated with AS A system of classification criteria of spondyloarthropathies  was experimented in three studies . They have permitted to measure its specificity which is 86.6 p. cent and its sensitivity which is 90 p. cent . This system permits to compare theory and clinical practice and also to classify disease not yet classified . The positive and negative predictive values of these tests remain to be vali date d and assessed , with a multicenter study including patients affected or not with spondyloarthropathy , in order to determine whether they can also be used as a diagnosis tool Forty-two patients with ankylosing spondylitis were entered into a double-blind study to compare treatment with indomethacin and a new non-steroidal anti-inflammatory drug , nabumetone . Clinical , laboratory and side-effect profiles were measured over a three month period . Both drugs were effective in relieving pain and morning stiffness , indomethacin was better in alleviating general stiffness , nabumetone result ed in less side-effects . Objective measurements of spinal movements revealed no difference between the two drugs . Nabumetone , available as Relifex , appears as effective as indomethacin in relieving the symptoms of ankylosing spondylitis and is possibly better tolerated 98 patients with reversible , definite , active ankylosing spondylitis were selected for this study . 49 patients were treated with N-(2,6-dichloro-m-tolyl)anthranilic acid , sodium salt ( meclofenamate sodium , Meclomen ) and 49 patients with indometacin . Following a single-blind baseline period on placebo , patients received either 200 mg meclofenamate sodium per day or 100 mg indometacin per day for one week , in the second week the doses were increased to 250 mg meclofenamate sodium and 125 mg indometacin and from the third through the eight week 300 mg meclofenamate sodium and 150 mg indometacin were given . The results of this double-blind study showed that similar improvement in mobility of the vertebral column and spondylitic pain could be achieved with meclofenamate sodium and indometacin in patients with ankylosing spondylitis . Although both treatments were well tolerated fewer  meclofenamate sodium patients reported adverse reactions than did those who had received indometacin . It is concluded that meclofenamate sodium offers an effective and safe alternative to indometacin in the treatment of patients with ankylosing spondylitis 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 BACKGROUND Each year , clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs ( NSAIDs ) . We assessed whether rofecoxib , a selective inhibitor of cyclooxygenase-2 , would be associated with a lower incidence of clinical ly important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis . METHODS We r and omly assigned 8076 patients who were at least 50 years of age ( or at least 40 years of age and receiving long-term glucocorticoid therapy ) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily . The primary end point was confirmed clinical upper gastrointestinal events ( gastroduodenal perforation or obstruction , upper gastrointestinal bleeding , and symptomatic gastroduodenal ulcers ) . RESULTS Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis . During a median follow-up of 9.0 months , 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib , as compared with 4.5 per 100 patient-years with naproxen ( relative risk , 0.5 ; 95 percent confidence interval , 0.3 to 0.6 ; P<0.001 ) . The respective rates of complicated confirmed events ( perforation , obstruction , and severe upper gastrointestinal bleeding ) were 0.6 per 100 patient-years and 1.4 per 100 patient-years ( relative risk , 0.4 ; 95 percent confidence interval , 0.2 to 0.8 ; P=0.005 ) . The incidence of myocardial infa rct ion was lower among patients in the naproxen group than among those in the rofecoxib group ( 0.1 percent vs. 0.4 percent ; relative risk , 0.2 ; 95 percent confidence interval , 0.1 to 0.7 ) ; the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups . CONCLUSIONS In patients with rheumatoid arthritis , treatment with rofecoxib , a selective inhibitor of cyclooxygenase-2 , is associated with significantly fewer clinical ly important upper gastrointestinal events than treatment with naproxen , a nonselective inhibitor OBJECTIVE To determine whether the effects of anti-tumor necrosis factor alpha ( TNFalpha ) in reducing the signs and symptoms of ankylosing spondylitis ( AS ) coincide with a reduction in spinal inflammation as detected by magnetic resonance imaging ( MRI ) . METHODS Pre- and postgadolinium T1 and STIR MR images of the spine were acquired at baseline and at week 24 in patients with AS who participated in a multicenter , r and omized , double-blind , placebo-controlled study . Patients were r and omly assigned at an 8:3 ratio to receive infusions of infliximab ( 5 mg/kg ) or placebo at weeks 0 , 2 , and 6 and then every 6 weeks thereafter . MR images were obtained and evaluated independently by 2 readers who were blinded to the treatment allocation and time sequence of the images . RESULTS A total of 194 patients in the infliximab group and 72 patients in the placebo group had evaluable images at baseline and week 24 . About 80 % of the patients had at least 1 active spinal lesion at baseline , as assessed by MRI . The improvement in the MRI Activity Score after 6 months was significantly greater in the patients who received infliximab ( mean 5.02 , median 2.72 ) than in those who received placebo ( mean 0.60 , median 0.0 ) ( P < 0.001 ) . Almost complete resolution of spinal inflammation was seen in most patients who received infliximab , irrespective of baseline activity . CONCLUSION Patients with AS who received infliximab therapy showed a decrease in spinal inflammation as detected by MRI , whereas those who received placebo showed persistent inflammatory spondylitis BACKGROUND Non-steroidal anti-inflammatory drugs ( NSAIDs ) inhibit cyclo-oxygenase ( COX ) , which leads to suppression of COX-1-mediated production of gastrointestinal-protective prostagl and ins . Gastrointestinal injury is a common outcome . We compared the efficacy , safety , and tolerability of long-term therapy with celecoxib , a COX-1 sparing inhibitor of COX-2 , with diclofenac , a non-specific COX inhibitor . METHODS 655 patients with adult-onset rheumatoid arthritis of at least 6 months ' duration were r and omly assigned oral celecoxib 200 mg twice daily or diclofenac SR 75 mg twice daily for 24 weeks . Anti-inflammatory and analgesic activity and tolerability were assessed at baseline , every 4 weeks , and at week 24 . We assessed gastrointestinal safety by upper-gastrointestinal endoscopy within 7 days of the last treatment dose at centres where the procedure was available . Analysis was by intention-to-treat . FINDINGS 430 patients underwent endoscopy  ( celecoxib n=212 , diclofenac n=218 ) . The two drugs were similar in management of rheumatoid arthritis pain and inflammation . Gastroduodenal ulcers were detected endoscopically in 33 ( 15 % ) patients treated with diclofenac and in eight ( 4 % ) in the celecoxib group ( p<0.001 ) . The rate of withdrawal for any gastrointestinal-related adverse event , most commonly abdominal pain , diarrhoea , and dyspepsia , was nearly three times higher in the diclofenac-treated group than in the celecoxib group ( 16 vs 6 % ; p<0.001 ) . INTERPRETATION Celecoxib showed sustained anti-inflammatory and analgesic activity similar to diclofenac , with a lower frequency of upper gastrointestinal ulceration or gastrointestinal adverse events , and tolerability was better Background The Ankylosing Spondylitis Disease Activity Score ( ASDAS ) is a new composite index to assess disease activity in ankylosing spondylitis ( AS ) . It fulfils important aspects of truth , feasibility and discrimination . Criteria for disease activity states and improvement scores are important for use in clinical practice , observational studies and clinical trials and so far have not been developed for the ASDAS . Objective To determine clinical ly relevant cut-off values for disease activity states and improvement scores using the ASDAS . Methods For the selection of cut-offs data from the Norwegian disease modifying antirheumatic drug ( NOR-DMARD ) registry , a cohort of patients with AS starting conventional or biological DMARDs  , were used . Receiver operating characteristic analysis against several external criteria was performed and several approaches to determine the optimal cut-offs used . The final choice was made on clinical and statistical grounds , after debate and voting by Assessment of SpondyloArthritis international Society members . Crossvalidation was performed in NOR-DMARD and in Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy , a data base of patients with AS participating in a r and omised placebo-controlled trial with a tumour necrosis factor blocker . Results Four disease activity states were chosen by consensus : inactive disease , moderate , high and very high disease activity . The three cut-offs selected to separate these states were : 1.3 , 2.1 and 3.5 units . Selected cut-offs for improvement were : change ≥1.1 units for clinical ly important improvement and change ≥2.0 units for major improvement . Results of the crossvalidation strongly supported the cut-offs . Conclusions Cut-off values for disease activity states and improvement using the ASDAS have been developed . They proved to have external validity and a good performance compared to existing criteria A double-blind , cross-over comparison of Naprosyn ( naproxen ) 750 mg daily and Butacote ( enteric-coated phenylbutazone ) 300 mg daily was carried out in a multi-centre trial . Twenty-five patients , mostly male and under 40 years of age , were entered . After a 2-week period in which any existing anti-inflammatory drugs were tailed off , patients were entered into the trial and treated for 1 month with each drug . Patients were assessed at 4-weekly intervals . Both drugs significantly reduced morning stiffness . Morning pain and discomfort and wall-tragus distance were also significantly reduced by both drugs during the trial . Results of the Schober test showed improvement during both treatment periods . There were no overall statistically significant differences between the effects of the 2 drugs on objective parameters . However , overall subjective assessment of symptoms showed a greater improvement on Butacote . Treatment preferences by physician and subjective assessment by the patient both favoured  Butacote  but the difference between the 2 drugs was not statistically significant . Side effects were mostly of a minor nature . One patient had to discontinue the trial , due to indigestion while taking Butacote Abstract Objective : Control of airway inflammation is the cornerstone of asthma management . The aim of the present pilot study was to assess the effects of a leukotriene receptor antagonist ( LTRA ) added to a basic treatment of inhaled corticosteroids ( ICS ) and long-acting beta-agonist ( LABA ) on airway hyperresponsiveness , inflammation , and quality of life in well-controlled patients with asthma . Research design and methods : Seventeen patients ( age 18–65 , 11 women ) with well-controlled asthma presenting airway hyperresponsiveness to mannitol and methacholine challenge  were given add-on montelukast on a stable ICS + LABA for 4 weeks . Quality of life and selected parameters of airway inflammation were measured at baseline and at study end . ( Clinical Trials.gov ( NCT01725360 ) ) . Results : Adding montelukast to ICS + LABA result ed in an increase in mean FEV1 ( + 4.5 % , p = 0.057 ) , cumulated higher dose of mannitol ( + 32.5 % , p = 0.023 ) and methacholine ( + 17.2 % , 0.237 ) in the provocation test , lower airway reactivity with mannitol and methacholine ( response dose ratio ( RDR ) –50.0 % , p = 0.024 and –44.3 % , p = 0.006 , respectively ) , and improved airway sensitivity to mannitol and methacholine ( + 12.1 % , p = 0.590 and + 48.0 % , p = 0.129 for PD15 and PD20 FEV1 , respectively ) . Changes in inflammation parameters ( blood eosinophil count , serum eosinophil cationic protein , and exhaled nitric oxide ) were consistent with these findings . Asthma-related quality of life improved significantly in all domains and overall ( from 5.3 at baseline to 6.1 at the final visit , p < 0.001 ) . The main limitation was the absence of a control group . Conclusion : The consistency of the changes in airway hyperresponsiveness and inflammation as well as in quality of life observed with an add-on therapy with montelukast in well-controlled asthma patients during 4 weeks suggests that residual inflammation may represent an area for further improvement of asthma control to be explored in adequately powered r and omized controlled trials The r and omized , double-blind trial was carried out with 50 patients suffering from ankylosing spondylarthritis and belonging all to type B27 in the HLA system .  Tolfenamic acid ( 600 mg daily ) was effective as judged by subjective and numerous objective parameters and was preferable to indomethacin ( 75 mg daily ) . Indomethacin caused side effects more frequently than tolfenamic acid . In the indomethacin group 16 % of the patients interrupted the 6-month trial because of gastrointestinal complications . No discontinuation of treatment owing to adverse effects of tolfenamic acid occurred . Tolfenamic acid offers one new and good alternative for the medical treatment of ankylosing spondylarthritis Abstract Objectives : To determine the profile of risk of upper gastrointestinal toxicity during continuous treatment with , and after cessation of , non-steroidal anti-inflammatory drugs . Design : Cohort study with a prospect ively constructed , population based , record linkage data base containing details of exposure to all community dispensed non-steroidal anti-inflammatory drugs and also all admissions to hospital for upper gastrointestinal diagnoses . Setting : The population of Tayside , Scotl and . Subjects : 52 293 subjects aged 50 and over who received one or more non-steroidal anti-inflammatory between 1 January 1989 and 31 December 1991 and 73 792 subjects who did not receive one during the same period ( controls ) . Main outcome measures : Admission to hospital for upper gastrointestinal bleeding and perforation , and admission for other upper gastrointestinal diagnoses . Results : About 2 % of the non-steroidal anti-inflammatory cohort were admitted with an upper gastrointestinal event during the study period compared with 1.4 % of controls . The risk of admission for upper gastrointestinal haemorrhage and perforation was constant during continuous non-steroidal anti-inflammatory exposure and carried over after the end of exposure . The results were similar for admissions for all upper gastrointestinal events . Conclusion : This study provides evidence that non-steroidal anti-inflammatory toxicity persists with continuous exposure . There seems to be carryover toxicity after the end of prescribing . These findings have implication s for the management of patients requiring non-steroidal anti-inflammatory drugs . Key messages The risk of upper gastrointestinal toxicity associated with non-steroidal anti-inflammatory drugs is constant with continuous exposure Gastrointestinal toxicity continues for some time after treatment stops Such toxicity is common in older patients and patients with a history of upper gastrointestinal disease  Non-steroidal anti-inflammatory drugs should be avoided when possible ; when they are used the lowest effective dose of the least toxic drug should be used for the shortest period Flurbiprofen ( Ansaid , Upjohn ) , a potent new analgesic and anti-inflammatory agent , was compared with phenylbutazone in 90 patients with ankylosing spondylitis . In this double-blind , r and omized , 26-week study , a total daily dose of 200 mg of flurbiprofen , administered three times daily , was as effective as 300 mg of phenylbutazone in controlling the pain and other symptoms of ankylosing spondylitis . In some patients , symptoms were adequately controlled by 150 mg of flurbiprofen per day , administered twice daily . There were no statistically significant differences between flurbiprofen and phenylbutazone in the investigators ' and patients ' assessment s of improvement at all key follow-up periods . In addition , there were no consistently significant differences between drugs in the efficacy pain scales and quantitative measurements studied . Flurbiprofen was well tolerated in doses of up to 300 mg per day , and no clinical ly significant laboratory abnormalities were detected . Flurbiprofen appears to be an excellent alternative to phenylbutazone in the management of patients with ankylosing spondylitis Classification criteria for most of the disorders belonging to the spondylarthropathy group already exist . However , the spectrum of spondylarthropathy is wider than the sum of these disorders suggests . Seronegative oligoarthritis , dactylitis or polyarthritis of the lower extremities , heel pain due to enthesitis , and other undifferentiated cases of spondylarthropathy have been ignored in epidemiologic studies because of the inadequacy of existing criteria . In order to define classification criteria that also encompass patients with undifferentiated spondylarthropathy , we studied 403 patients with all forms of spondylarthropathy and 674 control patients with other rheumatic diseases . The diagnoses were based on the local clinical expert 's opinion . The 403 patients included 168 with ankylosing spondylitis , 68 with psoriatic arthritis , 41 with reactive arthritis , 17 with inflammatory bowel disease and arthritis , and 109 with unclassified spondylarthropathy . Based on statistical analysis and clinical reasoning , we propose the following classification criteria for spondylarthropathy : inflammatory spinal pain or synovitis ( asymmetric or predominantly in the lower limbs ) , together with at least 1 of the following : positive family history , psoriasis , inflammatory bowel disease , urethritis , or acute diarrhea , alternating buttock pain , enthesopathy , or sacroiliitis as determined from radiography of the pelvic region . These criteria result ed in a sensitivity of 87 % and a specificity of 87 % . The proposed classification criteria are easy to apply in clinical practice and performed well in all 7 participating centers . However , we regard them as preliminary until they have been further evaluated in other setting Fenoprofen , 600 mg , three times daily , was compared with phenylbutazone , 100 mg , three times daily , in 30 patients suffering from ankylosing spondylitis in a double-blind cross-over study . Assessment s were made after an initial washout period and after each month-long treatment period . Phenylbutazone significantly improved morning stiffness , finger-to-floor distance , chest expansion , overall joint pain , spinal pain , the physician 's assessment of disease activity and ESR . Only chest expansion was significantly improved by fenoprofen , and phenylbutazone was significantly better than fenoprofen in its effects on finger-to-floor distance , morning stiffness , overall joint pain , spinal pain and the physician 's assessment of disease activity . Side-effects were of a minor nature apart from one patient who developed rectal bleeding on phenylbutazone which recurred on rechallenging CONTEXT In vitro studies have shown that celecoxib inhibits cyclooxygenase 2 ( COX-2 ) but not COX-1 , suggesting that this drug may have anti-inflammatory and analgesic activity without adverse upper gastrointestinal ( GI ) tract effects that result from COX-1 inhibition . OBJECTIVE To test whether celecoxib has efficacy as an anti-inflammatory and analgesic with reduced GI tract mucosal damage compared with conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis . DESIGN R and omized , multicenter , placebo-controlled , double-blind trial lasting 12 weeks , with follow-up at weeks 2 , 6 , and 12 , from September 1996 thorugh February 1998 . SETTING Seventy-nine clinical sites in the United States and Canada . PATIENTS A total of 1149 patients aged 18 years or older with symptomatic rheumatoid arthritis who met inclusion criteria were r and omized ; 688 ( 60 % ) of these completed the study . INTERVENTIONS Patients were r and omized to receive celecoxib , 100 mg , 200 mg , or 400 mg twice per day ( n = 240 , 235 , and 218 , respectively ) ; naproxen , 500 mg twice per day ( n = 225 ) ; or placebo ( n = 231 ) . MAIN OUTCOME MEASURES Improvement in signs and symptoms of rheumatoid arthritis as assessed using st and ard measures of efficacy and GI tract safety as assessed by upper GI tract endoscopy before and after treatment , compared among treatment groups . RESULTS All dosages of celecoxib and naproxen significantly improved the signs and symptoms of arthritis compared with placebo .  Maximal anti-inflammatory and analgesic activity was evident within 2 weeks of initiating treatment and was sustained throughout the 12 weeks . The incidence of endoscopically determined gastroduodenal ulcers in placebo-treated patients was 4 ( 4 % ) of 99 , and the incidences across all dosages of celecoxib were not significantly different ( P>.40 ) : 9 ( 6 % ) of 148 with 100 mg twice per day , 6 ( 4 % ) of 145 with 200 mg twice per day , and 8 ( 6 % ) of 130 with 400 mg twice per day . In contrast , the incidence with naproxen was 36 ( 26 % ) of 137 , significantly greater than either placebo or celecoxib ( P<.001 ) . The overall incidences of GI tract adverse effects were 19 % for placebo ; 28 % , 25 % , and 26 % for celecoxib 100 mg , 200 mg , and 400 mg twice per day , respectively ; and 31 % for naproxen . CONCLUSION In this study , all dosages of celecoxib were efficacious in the treatment of rheumatoid arthritis and did not affect COX-1 activity in the GI tract mucosa as evidence d by less frequent incidence of endoscopic ulcers compared with naproxen A double-blind cross-over study in 35 patients with ankylosing spondylitis was carried out comparing flurbiprofen ( 150 mg daily)—a new non-steroidal anti-inflammatory agent — with phenylbutazone ( 300 mg daily ) over a four-week period . Flurbiprofen was well tolerated and shown to have therapeutic efficacy approaching that of phenylbutazone . The results suggest that flurbiprofen may prove a valuable alternative in the treatment of ankylosing spondylitis , and longterm efficacy and tolerance studies are clearly indicated 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 A 2-year r and omized controlled trial was performed to test the hypothesis that long-term , continuous treatment with nonsteroidal antiinflammatory drugs ( NSAIDs ) , in comparison with NSAID treatment on dem and only , influences radiographic progression in patients with ankylosing spondylitis ( AS ) . METHODS Patients with AS ( n = 215 ) , who had previously participated in a 6-week , r and omized , double-blind clinical trial that compared  celecoxib , ketoprofen , and placebo , were r and omly allocated to receive either continuous treatment with NSAIDs or on-dem and treatment with NSAIDs for a period of 2 years . All patients began treatment with celecoxib , at a starting dosage of 100 mg twice daily ; patients could increase this dosage to 200 mg twice daily or could switch to another NSAID while maintaining the same treatment strategy . Structural changes were assessed by radiographs of the lumbar and cervical spine and scored according to the modified Stoke Ankylosing Spondylitis Spine Score by one observer who was blinded to the treatment strategy and temporal order of the radiographs . Statistical analyses included a between-group comparison of 1 ) radiographic progression scores ( by Mann-Whitney U test ) , 2 ) time-averaged values of variables reflecting signs and symptoms of AS ( by linear regression analysis ) , and 3 ) the frequency of reported site-specific adverse events ( by chi-square test or Fisher 's exact test , as appropriate ) . RESULTS Complete sets of radiographs were available for 76 of the 111 patients in the continuous-treatment group and for 74 of the 104 patients in the on-dem and group . The mean + /- SD scores for radiographic progression were 0.4 + /- 1.7 in the continuous-treatment group and 1.5 + /- 2.5 in the on-dem and treatment group ( P = 0.002 ) . Parameters reflecting signs and symptoms were not statistically significantly different between groups . The between-group difference in radiographic progression did not disappear after adjusting for baseline values of radiographic damage or disease activity variables and for time-averaged values of disease activity variables , nor after input of missing data . Relevant adverse events tended to occur more frequently in the continuous-treatment group than in the on-dem and group ( for hypertension , 9 % versus 3 % ; for abdominal pain , 11 % versus 6 % ; for dyspepsia , 41 % versus 38 % ) , but the differences were not statistically significant . CONCLUSION A strategy of continuous use of NSAIDs reduces radiographic progression in symptomatic patients with AS , without increasing toxicity substantially A r and omized study was performed on 24 patients with ankylosing spondylitis to compare the efficacy and tolerability of 20 mg tenoxicam daily with 50 mg diclofenac twice daily . There were 6 withdrawals from the group taking tenoxicam and 4 from the diclofenac group . Depression in 1 patient taking tenoxicam was the only significant adverse event . Both drugs were otherwise well tolerated . Tenoxicam and diclofenac were rated as good or excellent by 27 % and 55 % of patients , respectively . Global assessment , pain and duration of morning stiffness were improved with both drugs but this improvement was not statistically significant and there was no statistically significant difference between the two groups . This study confirms that tenoxicam is effective and well tolerated but larger numbers would be required to detect a small difference between groups The efficacy and tolerance of 1200 mg/day oxaprozin and 100 mg/day diclofenac sodium were compared in 40 patients with ankylosing spondylitis in a 6-week open study . Overall improvement was seen in the patients in both treatment groups . Oxaprozin-treated patients showed significant improvement in spontaneous pain of the vertebral spine and in morning stiffness after 6 weeks ' treatment . There were no statistically significant differences between the treatment groups . Therapy was discontinued in 10 patients ; five treated with oxaprozin ( three because of intolerance and two because of worsening of symptoms ) and five taking diclofenac sodium ( four because of intolerance and one because of worsening of symptoms ) . Five ( 25 % ) oxaprozin-treated patients and six ( 30 % ) diclofenac sodium-treated patients had side-effects , with gastro-intestinal disturbances and dizziness reported most frequently . There were no statistically significant differences between the groups in the frequency of side-effects . These results indicate that oxaprozin is a promising therapeutic agent for ankylosing spondylitis A double-blind , crossover trial was carried out to compare the effectiveness and tolerance of indoprofen  with indomethacin in the treatment of ankylosing spondylitis . Nineteen patients entered the study and 1 was withdrawn for reasons unrelated to therapy . Patients received 4-weeks ' treatment in r and om order , with 200 mg indoprofen 4-times daily and 25 mg indomethacin 4-times daily . Most subjective and objective clinical measurements of disease activity showed a comparable degree of improvement with either drug although few statistically significant changes were observed . There was no statistically significant difference between treatments and , although gastro-intestinal side-effects occurred more commonly with indoprofen , patients known to be intolerant of indomethacin had been excluded from this trial A double-blind crossover trial of fenclofenac was untertaken to compare the short-term effects of phenylbutazone ( Butacote ) therapy with fenclofenac therapy ( 1200 mg daily ) in 23 patients suffering from ankylosing spondylitis . The patients were r and omly allocated to each of the test drugs for a period of two weeks , following wash-out periods of paracetamol for four days . The results favoured Butacote therapy in a dosage of 300 mg daily in the expressed preferences of both the patients and the physicians conducting the trial . Butacote was also better tolerated , as no severe side-effects occurred during treatment , whereas five patients developed a widespread rash during the period of fenclofenac therapy . No significant differences were seen between the two drugs in terms of clinical measurements of pain , morning stiffness , spinal movements , chest expansion , and abduction of the hips .  Butacote was shown to cause some significant depletion of haemoglobin level , probably due to water retention , and Butacote also reduced the serum urate level to a significant degree Ximoprofen is a new propionic NSAID which has previously demonstrated its efficacy at a daily dose of 30 mg . The aim of the study was to evaluate the efficacy of different daily dosages of Ximoprofen in patients with active ankylosing spondylitis . For 2 weeks 5 parallel groups were studied : placebo and Ximoprofen at 5 , 10 , 20 and 30 mg daily . Response to treatment was defined as an improvement in pain ( VAS 100 mm ) of at least 50 % during the study . 285 out of the 332 screened patients were included . At the end of the study , the percentage of responders was higher in the Ximoprofen groups ( 54 % , 41 % , 53 % , 56 % in the 5 , 10 , 20 and 30 mg groups , respectively ) than in the placebo group ( 21 % ) . The clearest dose related effect of Ximoprofen observed occurred after one week of treatment . This study 1/confirms the efficacy of Ximoprofen at a 30 mg daily dosage , 2/shows the persistence of this efficacy at lower dosages , 3/suggests that ankylosing spondylitis is a sensitive and relevant human model to assess NSAIDs at an early stage of clinical evaluation OBJECTIVE To assess the efficacy , safety , and tolerability of etoricoxib , a cyclooxygenase 2 ( COX-2 ) selective inhibitor , administered continuously over 52 weeks for the treatment of ankylosing spondylitis ( AS ) . METHODS This 2-part , multicenter , double-blind , parallel-group , 52-week study evaluated 2 doses of etoricoxib ( 90 and 120 mg ) compared with naproxen at 1,000 mg . A 6-week , active-comparator- and placebo-controlled period ( part I ) was followed by a 46-week active-comparator-controlled period ( part II ) . The primary outcome measures ( on 100-mm visual analog scales ) were patient 's assessment of spine pain , patient 's global assessment of disease activity , and the Bath Ankylosing Spondylitis Functional Index . RESULTS Of the 387 patients r and omized to receive treatment , 301 ( 77.8 % ) completed part I and 284 ( 75.9 % ) completed part II . Compared with placebo over 6 weeks , those receiving 90 mg etoricoxib , 120 mg etoricoxib , and naproxen demonstrated significantly ( P < 0.001 ) greater improvement in all primary end points ; treatment effects ( expressed as the difference in least squares mean change versus placebo ) were 21 - 29 mm for spine pain , 18 - 25 mm for disease activity , and 11 - 15 mm for function . Compared with patients receiving naproxen , significantly greater improvement in all primary end points was demonstrated in the combined group receiving either 90 mg etoricoxib or 120 mg etoricoxib over 6 weeks , in each individual etoricoxib treatment group over 6 weeks , and in the combined etoricoxib group over 1 year ( all P < 0.05 ) ; results for secondary and exploratory end points were generally consistent with those from the primary analysis . Among all groups , there were no significant differences in the incidence of overall clinical , drug-related , or serious adverse experiences ( AEs ) and discontinuations due to AEs . Safety observations during part II were generally consistent with those in part I. CONCLUSION Etoricoxib at doses of 90 mg and 120 mg demonstrated superior efficacy compared with placebo over 6 weeks , and compared with naproxen over 1 year . These study results demonstrate that etoricoxib is generally safe , well-tolerated , and efficacious for the treatment of AS In a double lind test 60 patients with ankylosing spondylitis received either Azapropazone ( 30 patients ) or Indomethacin ( 30 patients ) during a period of three weeks . In the two well comparable groups the therapeutic effect was equally good . As the results show the Azapropazone group came out a little better concerning the finger-ground distance and the difference in circumference of thorax , and the Azapropazone group was favoured slightly by the general judgement of the patients . However , these differences are not relevant . The influence on the spontaneous pain in the daytime and during the night and the shifting of dorsal and lumbar vertebral column was equally good in both groups . The compatibility was good in 59 out of 60 patients . One patient had to stop the Azapropazone medication because of gastric trouble in the second week of treatment . This result shows that in most patients an adequate medication with Azapropazone or with Indomethacin leads to a distinct reduction of pain and even painlessness already after a 3 weeks ' treatment . This is particularly important regarding kinesiatrics . Indomethacin and Phenylbutazone are generally regarded as approved preparations in treatment of ankylosing spondylitis . If Azapropazone which , according to all previous reports has no hematotoxic effect like Phenylbutazone , had the same good effect in a double blind test as Indomethacin , this must be regarded as a very positive result . Concerning the good compatibility of Azapropazone , a change of drug is possible without a reduction of the effect 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 Ankylosing spondylitis affects about 1 % of the population . In the past , evaluation of therapy in the management of this disease has been hampered by the lack of availability of objective criteria for following the condition . By using recently developed measurements of spinal mobility and other variables we have compared sulindac , a recently introduced nonsteroidal antiinflammatory drug , and indomethacin in a double-blind six-month parallel study of 30 patients .  Sulindac and indomethacin have comparable efficacy and tolerance . Advantages of sulindac include a twice-a-day dose regimen OBJECTIVE To evaluate the short-term efficacy of celecoxib , a cyclooxygenase 2-specific inhibitor , in the treatment of ankylosing spondylitis ( AS ) . METHODS The study was a 6-week r and omized , double-blind , placebo-controlled trial with 3 treatment arms : placebo , ketoprofen 100 mg twice daily , and celecoxib 100 mg twice daily . Patients who had AS according to the modified New York criteria , without peripheral synovitis and with active disease ( pain > or = 40 mm on a 100-mm visual analog scale [ VAS ] and an increase in pain of at least 30 % after nonsteroidal antiinflammatory drug withdrawal ) were eligible for study . Primary outcome measures were change in pain intensity ( VAS ) and change in functional impairment ( Bath Ankylosing Spondylitis Functional Index [ BASFI ] ) . RESULTS Of the 246 r and omized patients , 76 were allocated to receive placebo , 90 ketoprofen , and 80 celecoxib . There were no statistically significant differences between treatment groups at study entry . During the 6 weeks of the study , the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group , with a trend in favor of celecoxib when the 2 active treatments were compared . The mean changes were -13 mm , -21 mm , and -27 mm ( P = 0.006 ) for pain and 1 , -6 , and -12 ( P = 0.0008 ) for BASFI score in the placebo , ketoprofen , and celecoxib groups , respectively . During treatment , the number of patients reporting epigastric pain was 6 ( 8 % ) , 13 ( 14 % ) , and 10 ( 13 % ) in the placebo , ketoprofen , and celecoxib groups , respectively . CONCLUSION The results of this study confirm the clinical ly relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage , with significant improvement of both pain and function in patients with AS 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 Preliminary studies of flurbiprofen , a newly introduced anti-inflammatory agent , have shown that it exerts some anti-inflammatory and analgesic effects in man when compared with placebo and is relatively well tolerated ( Chalmers , Cathcart , Kumar , Dick and Buchanan , 1972 ) . The purpose of this paper is to compare the effects of flurbiprofen , indomethacin , and placebo under double-blind conditions in a group of patients with ankylosing spondylitis Objectives : To evaluate various validity aspects of four disease activity scores ( ASDAS ) for ankylosing spondylitis ( AS ) in comparison with the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , its individual components and physician and patient global assessment of disease activity . Methods : The analyses were performed in two cohorts of patients with AS : ( 1 ) the NOR-DMARD data base which includes patients starting on a disease-modifying antirheumatic drug or tumour necrosis factor ( TNF ) blocker and ( 2 ) patients participating in double-blind placebo controlled r and omised clinical trials with TNF blockers in four centres . Discrimination between patients with low versus high disease activity according to various definitions and between various levels of change were analysed as the st and ardised mean difference ( difference in the group means divided by the pooled SD of the group means ) and t score . Results : The four ASDAS versions were highly discriminatory in differentiating patients with different levels of disease activity and patients with different levels of change . The ASDAS scores outperformed the BASDAI and its single components in all setting s : patient- or physician-based , reflecting status or change , with normal or raised C-reactive protein ( CRP ) , in the presence or absence of peripheral arthritis . There were no major differences between the four ASDAS scores . Based on feasibility , the ASAS membership selected the ASDAS version which included back pain , duration of morning stiffness , patient global assessment , peripheral joint complaints and CRP as the preferred version . Conclusions : The ASDAS is a vali date d , highly discriminatory instrument for assessing disease activity in AS , including patient-reported outcomes and CRP levels In a parallel , double-blind and r and omized trial of 6-weeks ' duration , flurbiprofen ( 150 mg to 200 mg daily ) was compared with indomethacin ( 75 mg to 100 mg daily ) in the management of 26 patients with active ankylosing spondylitis . None of the patients in either group withdrew from the study because of lack of efficacy of the drugs . Both drugs were equally effective in the relief of pain and tenderness of the affected joints . Overall subjective improvement , assessed by the patient and the investigator at the end of the trial , was present in 90 % of the patients in the flurbiprofen group and in 75 % of those in the indomethacin group . The mean values of all the spinal motion tests improved in the flurbiprofen group but not in the indomethacin group . Statistically significant improvement in the Schober test was achieved in the flurbiprofen group and in chest expansion in the indomethacin group . Characteristic untoward effects related to the central nervous system and gastro-intestinal tract were present in a few patients in both groups 27 patients with ascertained ankylosing spondylitis experiencing constant after-midnight-pain received , following three medication-free days , in a double blind , r and omized , cross-over fashion indometacin ( 100 g/day ) and d-2-(6'-methoxy-2'-naphthyl)-propionic acid ( naproxen ) ( 500 mg/day ) , as suppositories , for a period of six days each . The intensity of the night-pain was recorded daily . Naproxen was shown to be equally effective as indometacin in alleviating the after-midnight backache of ankylosing spondylitis . Side effects occurred under indometacin in 5 cases , under naproxen in 3 cases 1 Isoxicam , 200 mg once daily , was compared to ketoprofen , 100 mg three times daily , in 19 patients ( 16 males , three females ) with ankylosing spondylitis in a 30-day , double-blind study conducted in two centres . 2 Improvements from baseline to final assessment were noted after both isoxicam and ketoprofen in most clinical variables , with isoxicam , in general , being more effective than ketoprofen . 3 Isoxicam was significantly superior to ketoprofen in reducing pain and was judged by both patients and physicians to be superior overall to ketoprofen . 4 Of the 13 patients who expressed a preference , 10 preferred isoxicam . 5 Typical NSAID side effects were encountered with both drugs OBJECTIVES To demonstrate the non-inferiority of celecoxib compared with diclofenac in subjects with ankylosing spondylitis ( AS ) . METHODS The basis of the present work was a 12-week r and omised , double-blind , controlled study in active AS subjects with three treatment arms : celecoxib 200 mg once a day , celecoxib 200 mg twice a day , and diclofenac SR 75 mg twice a day . The primary efficacy endpoint was the change from baseline in global pain intensity on a visual analogue scale ( VAS ) at week 12 . Secondary endpoints covered changes in disease activity , functional and mobility capacities , and adverse events . RESULTS A total of 458 subjects were r and omly assigned to either celecoxib 200 mg once a day ( n = 153 ) , celecoxib 200 mg twice a day ( n = 150 ) , or diclofenac ( n = 155 ) . Least square ( LS ) mean changes from baseline at week 12 on a pain VAS were clinical ly relevant in all treatment groups ( celecoxib 200 mg once a day : -29.1 mm ; celecoxib 200 mg twice a day:-31.7 mm ; diclofenac:-32.7 mm ) and non-inferior when compared to diclofenac . Ankylosing Spondylitis Assessment Study group 20 % ( ASAS 20 ) response and mean improvement in Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) scores at week 12 were numerically better on celecoxib 200 mg twice a day ( 59.7 % and -1.32 points ) and on diclofenac ( 60.2 % and -1.48 points ) than on celecoxib 200 mg once a day ( 46.0 % and -0.99 points ) . The incidence of gastrointestinal adverse events was significantly higher on diclofenac ( 28.4 % ) than on celecoxib 200 mg once a day ( 15.0 % ) or 200 mg twice a day ( 16.7 % ) . CONCLUSIONS The efficacy of celecoxib 200 mg once a day and 200 mg twice a day was comparable to that of diclofenac 75 mg twice a day with respect to pain reduction .  Celecoxib 200 mg twice a day and diclofenac reduced some parameters associated with inflammation more effectively than celecoxib 200 mg once a day . Treatment was well tolerated , with celecoxib ( either dose ) exhibiting less frequent gastrointestinal adverse events than diclofenac Benoxaprofen ( 600 mg once daily ) has been compared to indomethacin ( 25 mg 3 times daily ) in a double-blind crossover study of 20 patients with active ankylosing spondylitis ( AS ) . The clinical improvement was comparable with both drugs ; 6 patients preferred benoxaprofen and 7 patients indomethacin . Although 2 patients discontinued benoxaprofen because of lack of effect , no upper gastrointestinal side effects were reported with this drug . Benoxaprofen is an alternative to indomethacin in the treatment of AS 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 Summary Flurbiprofen ( 150–200 mg daily ) and phenylbutazone ( 300–400 mg daily ) were compared in the management of 27 patients with active ankylosing spondylitis . This was a parallel , double-blind , and r and omized trial of 6 weeks duration . Both drugs were equally effective in the relief of pain and tenderness of the affected joints . Overall subjective improvement , assessed by the patient and the investigator at the end of the trial , favored phenylbutazone , but it did not reach a statistically significant level . The mean values of the endpoint parameters of spinal motion showed statistically significant improvement in both groups , except in the Schober test in the flurbiprofen group and chest expansion in the phenylbutazone group . Untoward effects characteristic of these drugs were found in a few patients OBJECTIVE To develop and compare c and i date improvement criteria for  anti-TNFalpha  treatment in ankylosing spondylitis with optimal discriminating capacity between treatment and placebo . METHODS Data from two r and omised controlled trials which included 99 patients treated with infliximab or etanercept  were used to evaluate 50 c and i date improvement criteria . These were developed on the basis of pain , patient 's global assessment , function , morning stiffness , spinal mobility , and C reactive protein . Different levels of improvement in each domain ( 20 - 60 % ) were used to define Boolean type criteria . These criteria were compared with different percentages of improvement on the BASDAI and with modified ASAS improvement criteria . Bootstrap methods were applied to calculate 95 % confidence intervals ( CI ) of the chi(2 ) test values to select the best c and i date improvement criteria . RESULTS The best performing improvement criteria were " 20 % improvement in five of six domains " ( chi(2 ) = 31.9 ( 95 % CI , 18.0 to 46.9 ) ) with a low placebo response of 2.9 % and a high response to infliximab of 67.7 % ; and " ASAS 40 % improvement " ( chi(2 ) = 26.5 ( 13.3 to 41.1 ) ) , with response to placebo of 5.7 % and response to infliximab of 64.7 % . The good discriminating capacity of the two improvement criteria was confirmed by the combined data set of the infliximab and etanercept trial . CONCLUSIONS The " five of six " improvement criterion has the advantage of including the objective domains spinal mobility and acute phase reactants , but requires only 20 % improvement . The ASAS 40 % improvement criterion has the advantage of setting a high threshold , but only in patient reported outcomes . The choice between these improvement criteria needs to be based on further validation from upcoming trials OBJECTIVE To develop criteria for symptomatic improvement in patients with ankylosing spondylitis ( AS ) , using outcome domain data from placebo-controlled clinical trials of nonsteroidal antiinflammatory drugs ( NSAIDs ) . METHODS Patient data from 5 short-term , r and omized , controlled trials were used to assess equivalence , reliability , and responsiveness of multiple items in the 5 outcome domains for AS treatment : physical function , pain , spinal mobility , patient global assessment , and inflammation . At least one measure per domain was responsive ( st and ardized response mean of > 0.5 ) , except for the spinal mobility domain , which was omitted from the criteria . We developed and tested c and i date improvement criteria in a r and om two-thirds subset from the 3 largest trials and used the remaining one-third for validation . These 3 largest trials included 923 patients ( 631 receiving NSAIDs , 292 in placebo groups ) . We selected the multiple domain definition that best distinguished NSAID treatment from placebo by chi-square test and that had a placebo response rate of < or = 25 % . RESULTS C and i date definitions were changes in single domains and in multiple measure indices , as well as combinations of improvements in multiple domains . Worsening in a domain was defined as a change for the worse of > or = 20 % and a net change for the worse of > or = 10 units on a scale of 0 - 100 . Partial remission ( for comparison purpose s ) was defined as an end-of-trial value of < 20/100 in each of the 4 domains . Among 20 c and i date criteria , change of > or = 20 % and > or = 10 units in each of 3 domains and absence of worsening in the fourth discriminated best in the development subset ( 51 % of patients improved with NSAIDs , 25 % with placebo ; chi2 = 36.4 , P < 0.001 ) . Results were confirmed in the validation subset . Almost all patients satisfying the definition of partial disease remission at the end of the trial had also improved by this criterion . Among all 923 patients , improvement rates using this criterion were 49 % for NSAID-treated patients and 24 % for placebo-treated patients . CONCLUSION Although further validation using data from new trials is still needed , we conclude that we have developed a clinical ly valid , easy-to-use measure of short-term improvement in AS In this double blind , crossover trial , 40 patients with ankylosing spondylitis were treated during two successive periods of 4 weeks each with either pirprofen 800 mg/day or ketoprofen 300 mg/day administered orally in a r and omized order . The efficacy of pirprofen and ketoprofen  was comparable , the results , as assessed by the clinician , were excellent or satisfactory in 53 % of both groups . Pirprofen was well tolerated by 71 % of the patients and  ketoprofen  by 59 % In a multicenter double-blind cross-over trial the therapeutic effect and the tolerance of d-2-(6'-methoxy-2'-naphthyl)-propionic acid ( naproxen ) and indometacin were compared including 46 patients with rheumatoid arthritis , 35 patients with ankylosing spondylitis and 19 patients with osteoarthrosis . Duration of treatment with both drugs was two to four weeks each . The daily dose of naproxen was 750 mg , that of indometacin l50 mg . In rheumatoid arthritis the combined clinical effect of indometacin was stronger than that of naproxen while both drugs had the same clinical effectiveness in ankylosing spondylitis and osteoarthrosis . When differentiating the total clinical effect as to indices of pain , inflammation and function , indometacin was shown to be superior in all three diseases with regard to pain index . On the other h and , naproxen showed a better effect in ankylosing spondylitis and osteoarthrosis than indometacin as to inflammation , and as to function in osteoarthrosis In a four week double-blind crossover study , flurbiprofen 200 mg daily was compared with naproxen 750 mg daily in the management of 30 patients with ankylosing spondylitis . Both treatments were found to be very effective in alleviating pain and stiffness . No significant difference in efficacy was discernible between the two drugs . Side-effects were more frequent with flurbiprofen . A small , but significant , increase in renal excretion of beta-n-acetyl glucosaminidase occurred during treatment with both naproxen and flurbiprofen . Although previous surveys have not shown evidence of renal damage , further surveillance of renal function in patients receiving long term treatment with these preparations to exclude possible renal impairment would be prudent A clinical evaluation of indomethacin employing a controlled , cross-over technique with an inert placebo was undertaken in 30 patients with ankylosing spondylitis . Patients were studied for the frequency and dose relationship of side effects and for the subjective response of morning stiffness , chronic spinal pain , acute exacerbations of pain and peripheral arthralgia . Objective evaluation assessed measured change in movements of the cervical and lumbar spines , in chest expansion and in the range of movement of involved peripheral joints . Evaluation of the results indicated that a significant number of patients experienced side effects in the form of headache and dizziness while receiving indomethacin in doses above 150 mg . per day . Many other side effects reported by the patients were not found to occur at a statistically significant level . The significance of pulmonary infections encountered in three patients was review ed . Relief of chronic spinal pain and peripheral arthralgia occurred in 14 and 16 patients , respectively ( p < 0.05 ) . Relief of morning stiffness and acute exacerbations of pain , and increase in the range of movement of any of the segments of the spine or the involved peripheral joints were not significant ( p > 0.05 ) . Based on the results of this study , it is suggested that the role of indomethacin in the management of ankylosing spondylitis be re-evaluated and that the daily therapeutic dose of this drug which has been heretofore recommended be decreased Tenoxicam ( 20 mg/day ) and piroxicam ( 20 mg/day ) were compared in a double-blind , parallel group study over 4 weeks in 30 patients with ankylosing spondylitis . Both tenoxicam and piroxicam reduced spinal pain , but the improvement was greater with piroxicam . Tenoxicam and piroxicam were equally effective at improving duration of morning stiffness . Slight improvement was seen with other symptoms with both treatments . Patients were slightly more tolerant of piroxicam than tenoxicam and most patients elected to continue on their particular therapy at the end of the study Thirty-nine patients with ankylosing spondylitis participated in a r and omized , double-blind , double-dummy , multi-cross-over study with enteric-coated ( ECT ) and plain ( PT ) naproxen tablets . The duration of the study was 24 days with 6 treatment periods of 4 days . The majority of the patients were taking 750 mg naproxen daily . The mean plasma concentration of naproxen in the morning was 36 % higher with ECT ( p < 0.001 ) . No significant differences regarding duration of morning stiffness and night time pain were found in this patient category . The mean duration of morning stiffness was 116 minutes ( ECT ) and 125 minutes ( PT ) . We were not able to show correlation between plasma concentration of naproxen and duration of morning stiffness In this r and omized , double-blind study , 57 patients with ankylosing spondylitis were evaluated after 26 weeks of treatment with either flurbiprofen ( Ansaid , Upjohn ) or indomethacin . Flurbiprofen administered four times a day in a total daily dose of 200 mg was effective in controlling the pain and associated symptoms of ankylosing spondylitis . Pain was adequately controlled in some patients following a total daily dose of 100 mg of flurbiprofen administered twice a day . Flurbiprofen was as effective as  indomethacin  in most key efficacy measurements analyzed . The drug was well tolerated in doses of up to 300 mg per day , and no clinical ly significant laboratory abnormalities were detected . Flurbiprofen is an excellent treatment for the control of pain and inflammation in patients with ankylosing spondylitis The efficacy and tolerability of a new formulation of slow-release indomethacin tablet was compared in a double-blind cross-over manner with a conventional indomethacin capsule in 30 patients with ankylosing spondylitis .  Gastrointestinal side-effects and dizziness were less frequent during the slow-release tablet period than during the capsule period The relative effectiveness of six nonsteroidal anti-inflammatory agents was studied in 33 patients with rheumatoid arthritis and 32 patients with ankylosing spondylitis in a double-blind , r and omized , prospect i ve study employing a six-way multiple crossover design with six-week trials of each agent . In ankylosing spondylitis , naproxen , indomethacin , and fenoprofen calcium were the most effective agents . In rheumatoid arthritis , relatively little mean difference between drugs was found . Most of this difference could be attributed to compliance factors , which favored drugs that required only a small number of pills daily . Despite the small differences in effect , patients had strong preferences . More than 85 % of patients were still taking their preferred medication after a mean follow-up period of one year OBJECTIVE To evaluate the efficacy and tolerability of aceclofenac , a new nonsteroidal antiinflammatory drug , in patients with active ankylosing spondylitis ( AS ) . METHODS 310 out patients with active AS were enrolled in a 3 month , multicenter , parallel , double blind trial and were r and omly assigned to receive aceclofenac ( 200 mg daily ) or indomethacin ( 100 mg daily ) . They were evaluated after a washout period of 7 days , at baseline , 15 , 30 , 60 , and 90 days . RESULTS No significant differences were found between aceclofenac and indomethacin in the number of withdrawals due to lack of efficacy or adverse events . A repeated measures analysis ( ANOVA ) of patients who completed the trial showed no significant differences between either treatment . Within-group comparisons in an intention-to-treat analysis showed improvement ( p < 0.05 ) in all the primary efficacy variables : pain visual analog scale ( VAS ) ( 37 vs 41 % ) , morning stiffness ( 51 vs 46 % ) , modified Schober 's test ( 21 vs 16 % ) , C7-iliac crest line distraction ( 11 vs 14 % ) , lateral spinal flexion ( 6 vs 10 % ) , in aceclofenac and indomethacin treated patients , respectively . Other variables including chest expansion , occiput-to-wall , Likert pain score , use of analgesic rescue , and patient and physician global assessment , also showed significant improvement from baseline values . No significant differences between treatments were noted for any efficacy variable . Good to excellent improvement in pain ( 52 vs 64 % ) and morning stiffness ( 70 vs 68 % ) was observed in aceclofenac and indomethacin treated patients , respectively . Patients taking aceclofenac had significantly fewer central nervous system related adverse events than patients treated with indomethacin ( p < 0.001 ) . CONCLUSION Aceclofenac and indomethacin did not differ with respect to efficacy in the treatment of active AS , although aceclofenac was slightly better tolerated Benoxaprofen , 600 mg once daily , was compared with ketoprofen , 100 mg twice daily , in a double-blind parallel study of 23 patients with definite active ankylosing spondylitis . Results were assessed using the following measurements : day pain , night pain , and spinal stiffness . Spinal stiffness was determined by means of st and ard clinical tests . Patient 's evaluation and physician 's overall assessment at the end of therapy also were taken into account . Under these conditions , the therapeutic response for benoxaprofen was good/very good , 8 ; fair , 2 ; and no response , 2 . For ketoprofen , the response as good/very good , 5 ; fair 3 ; and no response 3 . This study shows that benoxaprofen provides very good therapeutic effectiveness in the treatment of ankylosing spondylitis . This is confirmed by the absence of any statistically significant difference between the results observed with benoxaprofen and with ketoprofen , a drug known to be of value in ankylosing spondylitis . The clinical and biologic tolerance of benoxaprofen in this study was quite satisfactory A series of 26 patients with ankylosing spondylitis have been included in a double-blind cross-over comparison of ketoprofen 200 mg daily and phenylbutazone 300 mg daily , each drug being given for 4 weeks , with paracetamol as a ' rescue drug ' . Six patients withdrew from the study : three on phenylbutazone and one on ketoprofen -- two defaulted treatment . Twenty patients ( 17 males and 3 females ) were eligible for assessment . Their ages ranged between 20 and 59 years ( mean 40.2 years ) . Patient characteristics were comparable in both groups . The results of this series indicate no suggestion of statistically significant differences in any of the nine movements measured . The only significant differences , both in favour of phenylbutazone , were in the  paracetamol consumption in the second treatment period in the group receiving ketoprofen first ( 0.01 greater than P greater than 0.005 ) and in the patients ' preference for phenylbutazone ( 0.005 greater than P greater than 0.001 ) . Adverse reactions were comparable in both groups Feprazone , a non-steroidal anti-inflammatory drug , was compared with indomethacin in a double-blind cross-over trial in 24 patients with ankylosing spondylitis , over eight weeks . Both regimes caused significant reduction in pain . There were fewer side-effects and more patient preferences with feprazone but these differences did not reach statistical significance OBJECTIVE To investigate the diagnostic value of magnetic resonance imaging ( MRI ) in the detection of early sacroiliitis . METHODS Twenty-five consecutive HLA-B27 positive patients with inflammatory low back pain and < or = grade 2 unilateral sacroiliitis on conventional radiography ( modified New York criteria ) were studied . Erythrocyte sedimentation rate , C-reactive protein , plain radiography ( PR ) , and MRI of the sacroiliac ( SI ) joints were obtained at study entry and PR of the SI joints after 3 years . Each radiograph and MR image set was interpreted independently . SI joints were scored according to the modified New York Criteria for radiological sacroiliitis .  MRI  scans were also scored for the presence of subchondral marrow edema . The relationship between > or = grade 2 sacroiliitis ( by modified New York criteria for radiological sacroiliitis ) shown on MRI and the subsequent development of > or = grade 2 sacroiliitis on PR after 3 years was investigated . RESULTS At study entry > or = grade 2 sacroiliitis was found on MRI in 36 of 50 SI joints . Edema was found in 20 of 50 SI joints . After 3 years > or = grade 2 sacroiliitis was found on PR in 21 of 44 SI joints . The positive predictive value of > or = grade 2 sacroiliitis on MRI for the development of > or = grade 2 sacroiliitis on PR after 3 years was 60 % ; sensitivity was 85 % and specificity 47 % . CONCLUSION Our data suggest that MRI of the SI joints can be used to identify sacroiliitis earlier than PR We report 2 independently-conducted family studies of HLA-B27 positive prob and s with ankylosing spondylitis ( AS ) , both of which support the view that the clinical spectrum of AS is broader than ordinarily assumed , and should include individuals who have symptomatic disease but who do not show radiologic evidence of abnormalities of the sacroiliac joints or the spine . In the Clevel and study of 100 relatives of 30 B27 positive AS prob and s , 9 relatives did not show radiologic abnormalities of the sacroiliac joints or the spine but had symptoms of chronic inflammatory back pain  previously reported to be characteristic of AS . These 9 relatives were all subsequently found to possess B27 , in contrast with only 27 of 60 asymptomatic relatives ( P less than 0.01 ) . In the Leiden study of 101 relatives of 20 r and omly chosen B27 positive AS prob and s , 13 of 86 relatives without radiographic evidence of sacroiliitis reported " thoracic pain and stiffness , " as defined in the Rome criteria for AS . Twelve of these 13 symptomatic relatives were B27 positive . In contrast , among the remaining 73 relatives , only 33 were B27 positive ( P less than 0.01 ) . The occurrence of these characteristic spondylitic symptoms in B27 positive , but not B27 negative , relatives of AS prob and s suggests that the spectrum of the clinical manifestations of AS may include individuals with symptomatic disease , but without radiographic evidence of abnormalities of the sacroiliac joints or the spine . The relatively large number of females we found in this group suggests that women are more likely to manifest this variety of disease than are men BACKGROUND Cyclo-oxygenase (COX)-2-selective non-steroidal anti-inflammatory drugs ( NSAIDs ) and non-selective NSAIDs plus a proton-pump inhibitor ( PPI ) have similar upper gastrointestinal outcomes , but risk of clinical outcomes across the entire gastrointestinal tract might be lower with selective drugs than with non-selective drugs . We aim ed to compare risk of gastrointestinal events associated with celecoxib versus diclofenac slow release plus omeprazole . METHODS We undertook a 6-month , double-blind , r and omised trial in patients with osteoarthritis or rheumatoid arthritis at increased gastrointestinal risk at 196 centres in 32 countries or territories . Patients tested negative for Helicobacter pylori and were aged 60 years and older or 18 years and older with previous gastroduodenal ulceration . We used a computer-generated r and omisation schedule to assign patients in a 1:1 ratio to receive celecoxib 200 mg twice a day or diclofenac slow release 75 mg twice a day plus omeprazole 20 mg once a day . Patients and investigators were masked to treatment allocation . The primary endpoint was a composite of clinical ly significant upper or lower gastrointestinal events adjudicated by an independent committee . Analysis was by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00141102 . FINDINGS 4484 patients were r and omly allocated to treatment ( 2238 celecoxib ; 2246 diclofenac plus omeprazole ) and were included in intention-to-treat analyses . 20 ( 0.9 % ) patients receiving celecoxib and 81 ( 3.8 % ) receiving diclofenac plus omeprazole met criteria for the primary endpoint ( hazard ratio 4.3 , 95 % CI 2.6 - 7.0 ; p<0.0001 ) . 114 ( 6 % ) patients taking celecoxib versus 167 ( 8 % ) taking diclofenac plus omeprazole withdrew early because of gastrointestinal adverse events ( p=0.0006 ) . INTERPRETATION Risk of clinical outcomes throughout the gastrointestinal tract was lower in patients treated with a COX-2-selective NSAID than in those receiving a non-selective NSAID plus a PPI . These findings should encourage review of approaches to reduce risk of NSAID treatment . FUNDING Pfizer Objective To investigate the influence of non-steroidal anti-inflammatory drugs ( NSAIDs ) intake on radiographic spinal progression over 2 years in patients with ankylosing spondylitis ( AS ) and non-radiographic axial spondyloarthritis ( SpA ) . Methods 164 patients with axial SpA ( 88 with AS and 76 with non-radiographic axial SpA ) were selected for this analysis based on availability of spinal radiographs at baseline and after 2 years of follow-up and the data on NSAIDs intake . Spinal radiographs  were scored by two trained readers in a concealed r and omly selected order according to the modified Stoke Ankylosing Spondylitis Spine Score ( mSASSS ) system . An index of the NSAID intake counting both dose and duration of drug intake was calculated . Results High NSAIDs intake ( NSAID index≥50 ) in AS was associated with lower likelihood of significant radiographic progression defined as an mSASSS worsening by ≥2 units : OR=0.15 , 95 % CI 0.02 to 0.96 , p=0.045 ( adjusted for baseline structural damage , elevated C reactive protein ( CRP ) and smoking status ) in comparison with patients with low NSAIDs intake ( NSAID index<50 ) . This effect was most pronounced in patients with baseline syndesmophytes plus elevated CRP : mean mSASSS progression was 4.36±4.53 in patients with low NSAIDs intake versus 0.14±1.80 with high intake , p=0.02 . In non-radiographic axial SpA , no significant differences regarding radiographic progression between patients with high and low NSAIDs intake were found . Conclusion A high NSAIDs intake over 2 years is associated with retarded radiographic spinal progression in AS . In non-radiographic axial SpA this effect is less evident , probably due to a low grade of new bone formation in the spine at this stage
BACKGROUND Axial spondyloarthritis ( axSpA ) comprises ankylosing spondylitis ( radiographic axSpA ) and non-radiographic (nr-)axSpA and is associated with psoriasis , uveitis and inflammatory bowel disease .
Non-steroidal anti-inflammatory drugs ( NSAIDs ) are recommended as first-line drug treatment .