title: Antibodies to Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis in ankylosing spondylitis: effect of sulfasalazine treatment. Sulphasalazine in ankylosing spondylitis. Which is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Comparison of sulfasalazine and placebo for the treatment of axial and peripheral articular manifestations of the seronegative spondylarthropathies: a Department of Veterans Affairs cooperative study. [Treatment of ankylosing spondylitis with salazosulfapyridine. A controlled double-blind study in 60 patients]. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial Sulphasalazine in ankylosing spondylitis. A radiological, clinical and laboratory assessment Comparison of sulfasalazine and placebo in the treatment of ankylosing spondylitis. A Department of Veterans Affairs Cooperative Study. Randomized double-blind comparison of chimeric monoclonal antibody to tumor necrosis factor alpha (infliximab) versus placebo in active spondylarthropathy. The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years. Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin. Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis [Sulfasalazine in the treatment of ankylosing spondylitis]. Reductions in health-related quality of life in patients with ankylosing spondylitis and improvements with etanercept therapy. A controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect. Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients. A short-term follow-up of enthesitis and arthritis in the active phase of juvenile onset spondyloarthropathies. 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. Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study. Effects of etanercept versus sulfasalazine in early axial spondyloarthritis on active inflammatory lesions as detected by whole-body MRI (ESTHER): a 48-week randomised controlled trial Clinical Efficacy of Etanercept Versus Sulfasalazine in Ankylosing Spondylitis Subjects with Peripheral Joint Involvement
abstract: OBJECTIVE To make a longitudinal study of antibodies to Klebsiella pneumoniae in patients with ankylosing spondylitis ( AS ) and to assess treatment effects . As a comparison we measured antibodies of 2 other gut associated bacteria , Escherichia coli and Proteus mirabilis . METHODS In a double blind study in 84 Finnish out patients with AS before and after 26 weeks ' treatment with sulfasalazine or placebo  we measured serum antibodies to Klebsiella pneumoniae , E. coli and Proteus mirabilis with ELISA : Serum sample s of 100 healthy blood donors served as controls . RESULTS The levels of IgA class antibodies to all 3 bacteria were statistically significantly higher in the sera of the patients compared to the controls . During sulfasalazine treatment significant decreases were observed in concentrations of the IgA class antibodies to Klebsiella and E. coli whereas only a slight decrease was observed in the concentrations of IgA antibodies to Proteus mirabilis . There were no correlations between the clinical and laboratory results observed with sulfasalazine and decrease in concentrations of IgA class antibodies . CONCLUSION Our results agree with the role of gut associated lymphoid tissue in the pathogenesis of AS , but do not totally exclude Klebsiella pneumoniae as a specific agent contributing to the development of AS In recent years sulphasalazine has gained acceptance as an effective agent for the treatment of rheumatoid arthritis . Ankylosing spondylitis is a disease where remission inducing drugs so far have been lacking . In this double blind trial sulphasalazine was compared with placebo in 37 patients with ankylosing spondylitis . Evaluation after three months ' treatment showed reduction of inflammatory activity and improvement of clinical variables . The side effects were mild . The results suggest that sulphasalazine is a potentially effective and safe drug in the treatment of ankylosing spondylitis OBJECTIVE To compare the efficacy of sulfasalazine ( SSZ ) with its two moieties , 5-aminosalicylic acid ( ASA ) and sulfapyridine ( SP ) , in patients with active ankylosing spondylitis ( AS ) . METHODS A 26-week r and omized , observer-blinded , 2-center , controlled study of treatment with either SSZ , ASA , or SP was conducted in 90 patients with active AS . Patients were evaluated at baseline and at monthly intervals , using several clinical and laboratory measures of disease activity . A global assessment of treatment efficacy was made by both patients and observers at the end of the study period . RESULTS There were no significant changes in any of the parameters of disease activity in the ASA treatment group . Levels of serum IgG , IgA , and IgM fell significantly during treatment with SP , but none of the other changes reached statistical significance . Plasma viscosity and IgG and IgA levels fell significantly during treatment with SSZ , as did nocturnal spinal pain and overall spinal pain . Patients and observers reported a favorable outcome after treatment with SSZ or SP significantly more often than with ASA treatment . CONCLUSION SP appears to be the active moiety in AS , although there was a trend suggesting a better outcome in the SSZ group compared with the SP group , perhaps suggesting the importance of a common sulfonamide structure for efficacy OBJECTIVES To assess the effect of sulfasalazine ( SSZ ) on inflammatory back pain ( IBP ) due to active undifferentiated spondyloarthritis ( uSpA ) or ankylosing spondylitis in patients with symptom duration < 5 years . METHODS Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) > 3 from 12 centres were r and omly assigned to 24 weeks ' treatment with SSZ 2 g/day or placebo . The primary outcome variable was the change in BASDAI over 6 months . Secondary outcomes included measures of spinal pain , physical function and inflammation . RESULTS 230 patients ( 50 % men , age range 18 - 64 years , 67 % human leucocyte antigen B27 positive ) were treated with either SSZ 2x1 g/day or placebo for 6 months . Enthesitis was found in 50 % , and peripheral arthritis in 47 % of the patients . The mean ( SD ) BASDAI dropped markedly in both groups : by 3.7 ( 2.7 ) and 3.8 ( 2.4 ) , respectively , as did most secondary outcome measures . No noticeable difference in treatment was observed between groups . Patients with IBP and no peripheral arthritis had significantly ( p = 0.03 ) more benefit with SSZ ( BASDAI 5.1 ( 1.3 ) to 2.8 ( 2.3 ) ) than with placebo ( 5.2 ( 1.6 ) to 3.8 ( 2.4 ) ) . Spinal pain ( p = 0.03 ) and morning stiffness ( p = 0.05 ) improved with SSZ in these patients , but other secondary outcomes were not markedly different . CONCLUSION SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA ; however , SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis OBJECTIVE To determine if the peripheral articular manifestations of the seronegative spondylarthropathies ( SNSA ) respond differently than the axial manifestations to treatment with sulfasalazine ( SSZ ) . METHODS This is a re analysis of a previously reported series of r and omized , double-blind , placebo-controlled , multicenter trials comparing the effects of SSZ , 2,000 mg/day , and placebo on the axial and peripheral articular manifestations of ankylosing spondylitis ( AS ) , psoriatic arthritis ( PsA ) , and reactive arthritis ( ReA ; Reiter 's syndrome ) . Patients were classified as treatment responders on the basis of meeting predefined improvement criteria in 4 outcome measures : namely , patient and physician global assessment s in all patients , morning stiffness and back pain in patients with axial manifestations , and joint pain/tenderness scores and joint swelling scores in patients with peripheral articular manifestations . RESULTS Six hundred nineteen SNSA patients ( 264 AS , 221 PsA , and 134 ReA ) were studied . One hundred eighty-seven of these patients had only axial manifestations of their disease , while 432 patients had peripheral articular manifestations . Of the patients with axial disease , 40.2 % of the SSZ group and 43.3 % of the placebo group met the predefined response criteria ( P = 0.67 ) . Of the peripheral articular group , 59.0 % of the SSZ-treated patients and 42.7 % of the placebo-treated patients showed a response ( P = 0.0007 ) . CONCLUSION In a large group of affected individuals , the response of SNSA patients to SSZ appears to be related to the articular manifestations of their disease . These data demonstrate that the axial and peripheral articular manifestations of SNSA respond differently to treatment with SSZ . In SNSA patients with persistently active peripheral arthritis , SSZ is safe , well tolerated , and effective The efficacy of salazosulfapyridine ( SI ) has been recently reported in the course of peripheral arthritis in ankylosing spondylarthritis ( SPA ) , but is action on the axial forms of the disease was not known . We have therefore conducted a therapeutic trial in 60 patients suffering from SPA , without peripheral involvement clinical sign evoking an enterocolopathy . This double-blind study compared the activity of SI at a dose of 2 g/day with a placebo , for 6 months . Thirteen patients had to discontinue the treatment : 6 in the placebo group ( inefficacy : 3 cases , anemia : 1 case , epigastric pain : 1 case , rash : 1 case ) and 7 cases in the SI group ( inefficacy : 2 cases , nauseous : 3 cases , abdominal pain : 1 case , moderate elevation of transaminases : 1 case ) . These 13 patients were kept for the global analysis and considered as therapeutic failures . The treatment was considered effective in 15 out of 30 patients of group SI and in 30 patients on placebo ( p less than 0.02 ) . In addition , in group SI , a statistically significant decrease of the daily dose of non-steroid anti-inflammatory drugs  was observed ( -6.5 + /- 7.2 versus -2.4 + /- 6.4 in the placebo group , p less than 0.05 ) ; also was observed a decrease of the functional index ( -5.9 + /- 6.6 versus -1.9 + /- 5.7 in the group placebo , p less than 0.05 ) and of the serum level of immunoglobulin G ( -1.8 + /- 3.6 g/l versus + 0.8 + /- 2.9 in the placebo group , p less than 0.025 ) . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND There are few effective treatments for ankylosing spondylitis , which causes substantial morbidity . Because of the central role of tumor necrosis factor alpha in the spondyloarthritides , we performed a r and omized , double-blind , placebo-controlled trial of etanercept , a recombinant human tumor necrosis factor receptor (p75):Fc fusion protein , in patients with ankylosing spondylitis . METHODS Forty patients with active , inflammatory ankylosing spondylitis were r and omly assigned to receive twice-weekly subcutaneous injections of etanercept ( 25 mg ) or placebo for four months . The primary end point was a composite of improvements in measures of morning stiffness , spinal pain , functioning , the patient 's global assessment of disease activity , and joint swelling . Patients were allowed to continue taking nonsteroidal antiinflammatory drugs , oral corticosteriods ( < or = 10 mg per day ) , and disease-modifying antirheumatic drugs at stable doses during the trial . RESULTS Treatment with etanercept result ed in significant and sustained improvement . At four months , 80 percent of the patients in the etanercept group had a treatment response , as compared with 30 percent of those in the placebo group ( P=0.004 ) . Improvements over base-line values for various measures of disease activity , including morning stiffness , spinal pain , functioning , quality of life , enthesitis , chest expansion , erythrocyte sedimentation rate , and C-reactive protein , were significantly greater in the etanercept group . Longitudinal analysis showed that the treatment response was rapid and did not diminish over time . Etanercept was well tolerated , with no significant differences in rates of adverse events between the two groups . CONCLUSIONS Treatment with etanercept for four months result ed in rapid , significant , and sustained improvement in patients with ankylosing spondylitis UNLABELLED BACKGROUND Treatment options for patients with ankylosing spondylitis are few . We aim ed to assess the effectiveness of infliximab , an antibody to tumour necrosis factor (TNF)-alpha , in treatment of such patients . METHODS In this 12-week placebo-controlled multicentre study , we r and omly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab ( 5 mg/kg ) and 35 to placebo at weeks 0 , 2 , and 6 . One patient in the infliximab group was withdrawn from the study . Our primary outcome was regression of disease activity of at least 50 % . To assess response , we used vali date d clinical criteria from the ankylosing spondylitis assessment working group , including disease activity ( BASDAI ) , functional indices ( BASFI ) , metrology ( BASMI ) , and quality of life ( short form 36 ) . Analyses were done by intention to treat . FINDINGS 18 ( 53 % ) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50 % compared with three ( 9 % ) of 35 on placebo ( difference 44 % [ 95 % CI 23 - 61 ] , p<0.0001 ) . Function and quality of life also improved significantly on infliximab but not on placebo ( p<0.0001 and p<0.0001 , respectively ) . Treatment with infliximab was generally well tolerated , but three patients had to stop treatment because of systemic tuberculosis , allergic granulomatosis of the lung , or mild leucopenia . INTERPRETATION Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis . Since there are some potentially serious adverse effects , we recommend that this treatment mainly be used in co-operation with rheumatological centres Summary In a 12-month double-blind placebo-controlled trial , the effect of sulphasalazine was studied in 40 patients with ankylosing spondylitis . The treatment group showed significant improvement in pain , stiffness , sleep disturbance ( p<0.05 ) , finger/floor distance , erythrocyte sedimentation rate , C-reactive protein , orosomucoid and IgA levels ( p<0.01 ) . There was improvement in sleep disturbance ( p<0.05 ) , finger/floor distance and erythrocyte sedimentation rate ( p<0.01 ) in the placebo group . Sulphasalazine did not retard radiological progression as measured either by plain X-ray or computerised tomographic scans . Multiple analysis of variance did not show a significant difference in disease activity indicators between the 2 groups OBJECTIVE To determine whether sulfasalazine ( SSZ ) at a dosage of 2,000 mg/day is effective for the treatment of active ankylosing spondylitis ( AS ) that is not controlled with nonsteroidal antiinflammatory drug therapy . METHODS Two hundred sixty-four patients with AS were recruited from 15 clinics , r and omized ( double-blind ) to SSZ or placebo treatment , and followed up for 36 weeks . Treatment response was based on morning stiffness , back pain , and physician and patient global assessment s. RESULTS While longitudinal analysis revealed a trend favoring SSZ in the middle of treatment , no difference was seen at the end of treatment . Response rates were 38.2 % for SSZ and 36.1 % for placebo ( P = 0.73 ) . The Westergren erythrocyte sedimentation rate declined more with SSZ treatment than with placebo ( P < 0.0001 ) . AS patients with associated peripheral arthritis showed improvement that favored SSZ ( P = 0.02 ) . Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints . CONCLUSION SSZ at a dosage of 2,000 mg/day does not seem to be more effective than placebo in the treatment of AS patients with chronic , longst and ing disease .  SSZ is well tolerated and may be more effective than placebo in the treatment of AS patients with peripheral joint involvement . This effect is more pronounced in treatment of the peripheral arthritis in this subgroup of AS patients OBJECTIVE To confirm in a placebo-controlled trial the safety and efficacy profile of infliximab in short-term treatment of patients with active spondylarthropathy ( SpA ) . METHODS Forty patients with active SpA were r and omly assigned to receive an intravenous loading dose ( weeks 0 , 2 , and 6 ) of 5 mg/kg infliximab or placebo . Evaluations for efficacy and safety were performed at weeks 1 , 2 , 6 , 8 , and 12 . The primary end points of this study were the improvements in patient and physician global assessment s of disease activity on a 100-mm visual analog scale . RESULTS Both primary end points improved significantly in the infliximab group compared with the baseline value , with no improvement in the placebo group . As early as week 2 and sustained up to week 12 , there was a highly statistically significant difference between the values for these 2 end points in the infliximab versus the placebo group . In most of the other assessment s of disease activity ( laboratory measures , assessment s of specific peripheral and /or axial disease ) , significant improvements were observed in the infliximab group compared with the baseline value and compared with placebo . Minor adverse events not causing discontinuation were equally observed in both treatment groups . There was one severe drug-related adverse event , in which a patient developed disseminated tuberculosis . CONCLUSION Tumor necrosis factor alpha blockade with infliximab in patients with active SpA was well tolerated and result ed in significant clinical and laboratory improvements in this short-term , placebo-controlled study . However , the occurrence of tuberculosis in one patient necessitates strict inclusion criteria and long-term followup A 3-year placebo-controlled trial of sulphasalazine ( SASP ) in 89 patients with established AS ( including radiological sacroiliitis ) showed a reduced frequency of peripheral arthritis in the treated group but did not show any definite benefit in the maintenance of spinal mobility . Adverse effects causing treatment withdrawal occurred in five placebo-treated patients and eight SASP-treated patients , but 22 patients preferred to stop taking daily medication of unproven benefit for the full 3 years . The natural history of established AS suggested two groups of patients : the majority with principally spinal symptoms and infrequent peripheral arthritis or iritis , and a minority who tend to have recurrent extra-spinal problems OBJECTIVE Etanercept , a fully human tumor necrosis factor ( TNF ) receptor , is an effective treatment in patients with ankylosing spondylitis ( AS ) .  Sulfasalazine is frequently used for the treatment of both axial symptoms and peripheral symptoms of AS , and it has been the recommended therapy before the use of an anti-TNF agent when peripheral arthritis is present . Until now , no clinical trial has compared the efficacy and safety of a TNF blocker with that of sulfasalazine . This study was undertaken to compare the efficacy and safety of etanercept with that of sulfasalazine after 16 weeks of treatment in patients with axial and peripheral manifestations of AS . METHODS In this r and omized , double-blind study , patients received etanercept 50 mg once weekly ( n=379 ) or sulfasalazine titrated to a maximum of 3 gm/day ( n=187 ) for 16 weeks . The primary end point was the proportion of patients who achieved the Assessment of SpondyloArthritis international Society criteria for 20 % improvement ( ASAS20 ) at 16 weeks . Last observation carried forward was predefined for imputation of missing values . RESULTS The mean age of the patients was 41 years , 74 % were male , and the mean disease duration was 7.6 years . The proportion of ASAS20 responders at week 16 was greater among patients treated with etanercept compared with those treated with sulfasalazine ( 75.9 % versus 52.9 % ; P<0.0001 ) . As early as week 2 of treatment , etanercept was found to be more effective than sulfasalazine ( P<0.0001 ) in ameliorating both the axial symptoms and peripheral manifestations . Serious adverse events rarely occurred , and the rate of serious adverse events did not differ between groups . CONCLUSION In this population of patients with AS , etanercept was significantly more effective than sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints Serum levels of immunoglobulin A ( IgA ) and the complex immunoglobulin A-alpha 1 antitrypsin ( IgA-alpha 1AT ) were measured at the commencement and after 3 months of a double-blind , placebo-controlled trial of sulphasalazine ( SAS ) in patients with active ankylosing spondylitis ( AS ) . Twenty-eight patients were evaluated , 15 on sulphasalazine , 13 on placebo .  Significant falls were seen in both IgA ( p less than 0.01 ) and IgA-alpha 1AT ( p less than 0.001 ) in the actively treated patients . In addition , significant improvement in clinical and laboratory measures of disease were observed . It is concluded that SAS is effective in AS and modulates the immune response Purpose : To assess the effects of sulfasalazine in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis and chronic intestinal inflammation . Methods : Twenty-two patients with anterior uveitis associated with ankylosing spondylitis were studied . Ten patients were r and omised to receive oral sulfasalazine ( group 1 ) and 12 patients r and omised to no treatment ( group 2 ) ; all were followed for 3 years  . Blood-aqueous barrier permeability was determined by fluorophotometry and bowel biopsies were taken . Results : A statistically significant difference was observed between the two groups regarding the number of recurrences of uveitis ( p = 0.016 ) . The blood-aqueous barrier permeability was significantly higher during acute attacks in group 2 ( group 1 : 31.3 ± 26.4 × 10−4 min−1 vs group 2 : 66.2 ± 28.5 × 10−4 min−1 ; p = 0.019 ) but not during the disease-free period . We observed a higher incidence of chronic intestinal inflammation at the end of the study in group 2 ( group 1 : 3/8 vs group 2 : 7/9 , p = 0.153 ) . No relation was observed between blood-aqueous barrier permeability and the number of recurrences . The number of patients with severe persistent posterior synechiae at the end of the study was higher in group 2 ( group 1 : 4 patients before and 4 patients at the end ; group 2 : 4 patients before and 8 patients at the end ; p = 0.65 ) . Conclusion : Sulfasalazine may be beneficial in preventing recurrences and reducing the severity of anterior uveitis associated with ankylosing spondylitis Ninety-five patients with ankylosing spondylitis received either sulphasalazine ( less than or equal to 3 g/day ) or placebo for 24 weeks . The patients who received sulphasalazine showed significantly improved clinical parameters [ duration of morning stiffness ( p less than 0.05 ) , the number of painful and swollen joints ( less than 0.05 ) ] and laboratory parameters [ erythrocyte sedimentation rate ( p less than 0.001 ) , haptoglobin ( p less than 0.05 ) , IgG ( p less than 0.05 ) , IgA ( p less than 0.001 ) , IgM ( p less than 0.05 ) ] . No statistically significant differences were seen in the patients receiving placebo . The results suggest that sulphasalazine is effective for the treatment of patients with ankylosing spondylitis . In these patients , there was also a diminution of the daily dosage of nonsteroidal antiinflammatory drugs . In the majority of patients , clinical and laboratory improvements were expressed more pronouncedly in the peripheral form of ankylosing spondylitis than in the axial form , but statistically no significant differences were found between the two groups OBJECTIVE To assess the impact of ankylosing spondylitis ( AS ) on patient health-related quality of life ( HRQOL ) relative to both the general US and chronically-ill population s , and to evaluate whether etanercept therapy can reverse impairments in HRQOL due to AS . METHODS Two AS patient population s were evaluated : patients with AS from a US clinical trial who were r and omized to receive either etanercept ( n = 20 ) or placebo ( n = 20 ) for 16 weeks , and placebo-treated patients from a multinational sample who subsequently received etanercept ( n = 129 ) during a 48-week , open-label extension study . A sample from the US general population and patients with other medical conditions derived from the National Survey of Functional Health Status were used as comparators to evaluate the relative impact of active AS on HRQOL , as measured by the Short Form 36 ( SF-36 ) question naire . RESULTS At baseline , patients with AS in both the US and multinational sample s had significantly lower scores than the US general population on all 8 SF-36 scales . Compared with patients with other medical conditions , patients with AS had the lowest scores in the physical domains -- Physical Functioning , Role Physical , and Bodily Pain . Impairments in SF-36 scores for psychosocial domains , such as Social Functioning , Role Emotional , and Mental Health , were somewhat less pronounced in patients with AS . Treatment with etanercept significantly improved the HRQOL of patients with AS on all 8 SF-36 scales , especially in the same physical domains that showed the greatest impairments prior to treatment ( Physical Functioning , Role Physical , and Bodily Pain ) . CONCLUSION Patients with active AS despite conventional therapy have significantly reduced HRQOL across a wide range of domains . These reductions are most pronounced in the physical domains and exceed those seen in many other chronic diseases . Etanercept therapy significantly improves patient HRQOL , indicating that decrements in HRQOL due to AS may be at least partly reversible Sixty-two patients with long established but symptomatic ankylosing spondylitis were treated with sulphasalazine or matching placebo in a r and omized double-blind controlled trial for 48 weeks . There were no consistent significant differences between the treatment groups in clinical parameters despite multiple assessment s. Equivalent numbers in each group were able to decrease or stop non-steroidal anti-inflammatory drug ingestion during the study period ( four active , eight placebo ) . Side effects were reported more commonly in the sulphasalazine group ( 27 versus 17 , NS ) , but only 21 patients stopped treatment because of side effects ( 12 versus 9 , NS ) . Analysis of the subgroup with an initial ESR greater than 20 mm/h failed to show any persisting differences of response between sulphasalazine and placebo . We conclude that sulphasalazine therapy does not have a role in the treatment of chronic ankylosing spondylitis Sulphasalazine has been reported to be effective in ankylosing spondylitis with peripheral arthritis , but its efficacy in spondylitis is unknown . Thus 60 patients with active ankylosing spondylitis without peripheral arthritis or gastrointestinal symptoms were r and omly allocated to one of two therapeutic groups . One group received 2 g sulphasalazine daily for six months and the other a placebo .  Thirteen patients ( six given placebo and seven given sulphasalazine ) dropped out of the trial and were considered to be treatment failures . After six months ' follow up efficacy was rated as good or very good by 15 of the 30 patients given sulphasalazine and by only six of the 30 given placebo ( p less than 0.02 ) . Furthermore , in the patients given sulphasalazine the daily consumption of non-steroidal anti-inflammatory drugs , functional index , and plasma IgG concentrations had fallen significantly . These data suggest that sulphasalazine may be a safe and effective treatment for spondylitis in ankylosing spondylitis OBJECTIVE To describe the characteristics of enthesitis and arthritis in the active inflammatory stage of juvenile onset spondyloarthropathies ( SpA ) during a short-term follow-up . PATIENTS AND METHODS The study group included data of 33 patients with juvenile-onset SpA with enthesitis in > or = 3 sites , arthritis in > or = 4 joints , and erythrocyte sedimentation rate ( ESR ) of > or = 25 mm/h despite treatment , who participated in a 26-week , double-blind , sulfasalazine versus placebo trial that showed no significant differences between groups in regard to enthesitis and arthritis . RESULTS Twenty-seven boys and 6 girls ( mean age : 15.3 + /- 3.5 years ; mean disease duration : 4.1 + /- 2.7 years ) with the seronegative enthesopathy and arthropathy ( SEA ) syndrome ( n = 20 ) or ankylosing spondylitis ( AS ; n = 13 ) comprised the group . Throughout the study , the mean ( + /- SD ) number of swollen joints and tender entheses were 4.6 + /- 2.5 and 8.3 + /- 5.4 . The entheses and joints most frequently involved were the calcaneal attachments of the plantar fascia ( 87.9 % ) and Achilles tendon ( 81.8 % ) and the ankle ( 87.9 % ) and knee ( 72.7 % ) , respectively . There was pain in the cervical , thoracic , and lumbar spine in 39.4 % , 69.7 % , and 63.6 % of patients and in the sacroiliac joints in 48.5 % . Mid-foot involvement ( or tarsitis ) occurred in 29 patients ( 87.9 % ) . Except for the feet , the simultaneous occurrence of enthesitis and arthritis in other sites was rare . Overall , there were no significant differences between SEA syndrome and AS patients . CONCLUSIONS Disease activity shows a significant trend for entheses and joints of the feet and a significant prevalence of axial enthesitis in juvenile onset SpA. Mid-foot involvement appears to be the most characteristic and potentially , the most severe form of disease in these 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 OBJECTIVE To assess the efficacy and tolerability of sulfasalazine ( SSZ ) in the treatment of spondylarthropathy . METHODS We conducted a 6-month r and omized , placebo-controlled , double-blind , multicenter study of patients with spondylarthropathy whose disease had remained active despite treatment with nonsteroidal antiinflammatory drugs . Patients were treated with SSZ ( 3 gm/day ) or placebo . The primary efficacy variables were the physician 's and patient 's overall assessment s , pain , and morning stiffness . End points were analyzed in the intent-to-treat and completer patient population s ; the time course of effect was analyzed in the completer patient population . RESULTS Of the 351 patients enrolled , 263 ( 75 % ) completed the 6-month treatment period . The withdrawal rates were 35 ( 20 % ) and 53 ( 30 % ) in the placebo and SSZ groups , respectively . In the intent-to-treat analysis of end point efficacy , the between-treatment difference reached statistical significance only for 1 of the 4 primary outcome variables , the patient 's overall assessment of disease activity , for which 60 % of the patients taking SSZ improved by at least 1 point on a 5-point scale , in contrast to 44 % of the patients taking placebo .  Laboratory markers of inflammation also showed statistically significant change in favor of SSZ . In subgroup analysis , the most impressive effects were seen in patients with psoriatic arthritis , both for the 4 primary efficacy variables and for secondary efficacy variables such as the number of inflamed joints . Adverse events were more frequent in the SSZ group than the placebo group , but all were transient or reversible after cessation of treatment . CONCLUSION The results of this study show that SSZ had greater efficacy than placebo in the treatment of active spondylarthropathy , notably in patients with psoriatic arthritis Purpose To evaluate the potential of etanercept versus sulfasalazine to reduce active inflammatory lesions on whole-body MRI in active axial spondyloarthritis with a symptom duration of less than 5 years . Methods Patients were r and omly assigned to etanercept  ( n=40 ) or  sulfasalazine  ( n=36 ) treatment over 48 weeks . All patients showed active inflammatory lesions ( bone marrow oedema ) on MRI in either the sacroiliac joints or the spine . MRI was performed at weeks 0 , 24 and 48 and was scored for active inflammatory lesions in sacroiliac joints and the spine including posterior segments and peripheral enthesitis by two radiologists , blinded for treatment arm and MRI time point . Results In the etanercept group , the reduction of the sacroiliac joint score from 7.7 at baseline to 2.0 at week 48 was significantly ( p=0.02 ) larger compared with the sulfasalazine group from 5.4 at baseline to 3.5 at week 48 . A similar difference in the reduction of inflammation was found in the spine from 2.2 to 1.0 in the etanercept group versus from 1.4 to 1.3 in the sulfasalazine group between baseline and week 48 , respectively ( p=0.01 ) . The number of enthesitic sites also improved significantly from 26 to 11 in the etanercept group versus 24 to 26 in the sulfasalazine group ( p=0.04 for difference ) . 50 % of patients reached clinical remission in the etanercept group versus 19 % in the sulfasalazine group at week 48 . Conclusion In patients with early axial spondyloarthritis active inflammatory lesions detected by whole-body MRI improved significantly more in etanercept versus sulfasalazine-treated patients . This effect correlated with a good clinical response in the etanercept group Objective . Etanercept , a fully human tumor necrosis factor soluble receptor , is effective in treatment of ankylosing spondylitis ( AS ) . Current guidelines suggest sulfasalazine ( SSZ ) treatment as initial therapy for the management of patients with AS with peripheral arthritis versus therapy with biologics . We compared the efficacy of etanercept with SSZ in patients with AS with peripheral joint involvement . Methods . The efficacy of etanercept 50 mg once weekly was compared with that of SSZ up to 3 g daily in subjects with ≥ 1 swollen peripheral joint at baseline , using data from a 16-week r and omized double-blind study in subjects with AS .  Efficacy was assessed by the Assessment in AS criteria and the Bath AS Disease Activity , Functional , and Metrology indices . The last observation carried forward method was used for imputation of missing values . Results . Of 566 subjects included in original study , 181 ( etanercept 121 ; SSZ 60 ) had ≥ 1 swollen peripheral joint and 364 ( etanercept 250 ; SSZ 124 ) had none at baseline . AS patients treated with etanercept showed significantly greater improvement than those treated with SSZ in all joint assessment s regardless of swollen joint involvement . Conclusion . In this analysis , etanercept was significantly more effective than SSZ for management of patients with AS and peripheral joint involvement
target: There is not enough evidence to support any benefit of sulfasalazine in reducing pain , disease activity , radiographic progression , or improving physical function and spinal mobility in the treatment of AS .
  A statistically significant benefit in reducing the erythrocyte sedimentation rate and easing spinal stiffness was mentioned in the previous version .
  More withdrawals because of side effects occurred with sulfasalazine .
background: BACKGROUND Ankylosing spondylitis ( AS ) is a chronic inflammatory disease of unknown cause and affects mainly the spine , but can also affect other joints .
  Disease progression may result in loss of mobility and function .
  Sulfasalazine is a disease-modifying antirheumatic drug used in the treatment of AS .
  However , its efficacy remains unclear .
  This is an up date of a Cochrane review first published in 2005 .
  OBJECTIVES To evaluate the benefits and harms of sulfasalazine for the treatment of ankylosing spondylitis ( AS ) .