The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years. Which is the active moiety of sulfasalazine in ankylosing spondylitis? A randomized, controlled study. [Sulfasalazine in the treatment of ankylosing spondylitis]. 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. A controlled trial of sulphasalazine treatment of chronic ankylosing spondylitis: failure to demonstrate a clinical effect. Sulfasalazine in the prevention of anterior uveitis associated with ankylosing spondylitis Clinical efficacy and safety of etanercept versus sulfasalazine in patients with ankylosing spondylitis: a randomized, double-blind trial. Sulphasalazine in ankylosing spondylitis: a double blind controlled study in 60 patients. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Efficacy and safety of infliximab in patients with ankylosing spondylitis: results of a randomized, placebo-controlled trial (ASSERT). Clinical Efficacy of Etanercept Versus Sulfasalazine in Ankylosing Spondylitis Subjects with Peripheral Joint Involvement Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin. Sulfasalazine in the treatment of spondylarthropathy. A randomized, multicenter, double-blind, placebo-controlled study. A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis 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. Both structural damage and inflammation of the spine contribute to impairment of spinal mobility in patients with ankylosing spondylitis
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 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 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 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 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 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 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 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 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 The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease-modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated success in reducing AS disease activity in a limited number of clinical trials . The objective of this multicenter , r and omized , placebo-controlled study was to evaluate the efficacy and safety of infliximab in patients with AS . METHODS Patients were r and omly assigned to receive infusions of placebo or 5 mg/kg infliximab at weeks 0 , 2 , 6 , 12 , and 18 . Efficacy was assessed using the ASsessment in Ankylosing Spondylitis ( ASAS ) International Working Group criteria , the Bath Ankylosing Spondylitis Disease Activity Index ( BASDAI ) , night pain , patient 's global assessment , the Bath Ankylosing Spondylitis Functional Index ( BASFI ) , the Bath Ankylosing Spondylitis Metrology Index ( BASMI ) , chest expansion , the M and er enthesis index , the total swollen joint index , the C-reactive protein level , and the Short Form 36 ( SF-36 ) health survey question naire . The primary end point in this study was the proportion of patients with a 20 % improvement response according to the ASAS International Working Group criteria ( ASAS20 responders ) at week 24 . RESULTS Of the 357 patients screened , 201 were assigned to receive 5 mg/kg infliximab and 78 were assigned to receive placebo . After 24 weeks , 61.2 % of patients in the infliximab group were ASAS20 responders compared with 19.2 % of patients in the placebo group ( P < 0.001 ) . Clinical benefit was observed in patients receiving infliximab as early as week 2 and was maintained over the 24-week study period . Patients receiving infliximab also showed significant improvements in the BASDAI , BASFI , BASMI , chest expansion , and physical component summary score of the SF-36 . Adverse events were reported by 82.2 % of patients receiving infliximab and by 72.0 % of patients receiving placebo ; however , most adverse events in both treatment groups were mild or moderate in severity . CONCLUSION Infliximab was well tolerated and effective in a large cohort of patients with AS during a 24-week study period 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 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 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 The signs and symptoms of ankylosing spondylitis ( AS ) respond inadequately to nonsteroidal antiinflammatory drugs , corticosteroids , and disease modifying antirheumatic drugs in quite a number of patients . Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials . The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label r and omised study . Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group . Treatment with both etanercept and infliximab at the end of the study was effective , safe , and well tolerated OBJECTIVE To 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 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
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 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 ) .