Morning stiffness and the erythrocyte sedimentation rate/'sed' rate (ESR) decreased more in people taking sulfasalazine compared to those taking fake pills (lower ESRs usually mean less inflammation). For patients without peripheral arthritis (N = 34), no significant difference was found in these outcomes (but articular index and degree of joint swelling were not assessed) except back pain VAS‐100 mm (where 0=no pain, 100=severe), which was showed to significantly favour SSZ over placebo (MD ‐9.20, 95% CI ‐17.81 to ‐0.59) (Comparison 03). Among them one study (Taggart 1996) compared efficacy of SSZ with its two moieties, 5‐aminosalicylic acid and sulfapyridine. Objectives: sulfasalazine in improving the signs and symptoms of AS in the axial skeleton and peripheral joints. The proportion of patients with peripheral arthritis was the highest at 68% (it ranged from 66% to 0 in other trials). Side effects have been reported with sulfasalazine. Methods: Continuous data of Dougados 1986 presented in the present review were assumed and calculated from the original paper and possibly inaccurate. In conducting meta‐analysis, we assumed that these medians were equal to means and calculated the SDs from CIs. In addition, many trials used patient's subjective assessment as markers, eg duration of morning stiffness, pain severity which is liable to investigators' intention. Adverse effects Significant differences between intervention groups were found in pooled data of withdrawal for side effects (RR 1.50, 95% CI 1.04 to 2.15, NNH 23, 95% CI 10 to 288) and withdrawal for any reason (RR 1.33, 95% CI 1.03 to 1.73, NNH 17, 95% CI 8 to 180), favouring placebo group (Comparison 01.44,46, Additional table 3). Comparison 1 SSZ vs placebo, Outcome 9 Score of daily NSAIDs (change from baseline, usual dosage as 10). Comparison 1 SSZ vs placebo, Outcome 21 Joint pain/tenderness score (0‐198, the higher score the more severe disease) or number. For other criteria, we scored as A (yes), B (unclear) and C (no). Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause and belongs to a group of diseases known as spondyloarthropathies (SpA), which includes reactive arthritis, arthritis/spondylitis in inflammatory bowel disease, psoriatic arthritis/spondylitis and undifferentiated SpA. Comparison 1 SSZ vs placebo, Outcome 3 Improvement in back pain. Comparison 1 SSZ vs placebo, Outcome 35 Respond to treatment (based on both patient and physician assessment). 1. The strength of evidence in this review should be ranked as Gold level. All studies claimed that they included the patients with active disease but the definitions of active disease varied. Twelve studies met the inclusion criteria but only eleven were included in the data analysis. 5. was the outcome assessment blinded? There is "gold" level of evidence that sulfasalazine improves morning stiffness and the erythrocyte sedimentation rate (ESR) in people with ankylosing spondylitis. Comparison 1 SSZ vs placebo, Outcome 18 Fingers‐to‐floor test (cm). Side effects occur in some people and include stomach upset, skin rashes and mouth sores which may occasionally stop people from taking sulfasalazine. Jansen FM, Vavricka SR, den Broeder AA, de Jong EM, Hoentjen F, van Dop WA. But when NSAIDs are not working well disease modifying anti‐rheumatic drugs (DMARDs), such as sulfasalazine may be used. 1. was the study described as randomised? National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. All the dichotomous data presented in Table comparisons and data were according to intention‐to‐treat analysis. USA.gov. 3. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ. Further studies on AS patients at early disease stage, with higher ESR (or active disease) and peripheral arthritis are needed to verify the efficacy of SSZ in these patients and the efficacy related factors. It is the best studied DMARD used in AS, but its efficacy remains unclear. Does sulfasalazine work to treat ankylosing spondylitis and how safe is it? NLM The mean or median (depending on the trial) level of baseline ESR was the highest, with 42 mm/hr in SSZ and 46 mm/hr in placebo group (in other trials, ranged from 41 in SSZ and 43 in placebo to 13.5 in SSZ and 11.0 in placebo). 6. was there a description of withdrawals and drop‐outs? Among 469 patients receiving SSZ, severe adverse reaction was reported in one patient who developed a generalized, erythematous, raised, pruritic eruption which was associated nausea, anorexia and insomnia (Clegg 1996). Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 8 ESR (mm/hr). Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been the main treatment for AS and they have been shown to dramatically relieve the symptoms in some patients (Dougados 2002). Sulfasalazine is an anti-inflammatory drug and is also used to treat rheumatoid arthritis and ulcerative colitis, a type of inflammatory bowel disease. Comparison 1 SSZ vs placebo, Outcome 34 Improvement in physician global assessment. Time to event data were also used to describe peripheral joint symptoms in Kirwan 1993. Persistent oligoarthritis or polyarthritis are commonly treated with sulfasalazine or methotrexate. Across all AS patients, SSZ demonstrated some benefit in reducing ESR and easing morning stiffness, but no evidence of benefit in physical function, pain, spinal mobility, enthesitis, patient and physician global assessment. Thirteen studies were excluded from the review. Other outcomes remained similar. HHS 7. were the results analysed according to intention‐to‐treat? More people stopped taking sulfasalazine because of the side effects than when taking fake pills. There was significant heterogeneity among the trials (p<0.0001) ((Comparison 01.12). Sulfasalazine reduces spinal stiffness, peripheral arthritis, and the erythrocyte sedimentation rate (ESR), but there is no evidence that it improves spinal mobility, enthesitis, or … Another study (Clegg 1996) has separately analyzed the results of patients with peripheral arthritis (n = 77) and found more peripheral responses in SSZ than in placebo group (55.9% vs 30.2%, P = 0.023). More than 30 outcomes were assessed. doi: 10.1002/14651858.CD004800.pub2. 3. were the participants blinded? There were clear descriptions of withdrawal and drop‐out in all studies. This could be due to the large difference of ESR at baseline levels among the studies (Additional Table 01). Difference of selection criteria is likely one reason why SSZ demonstrated benefit in some trials but not in others. Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 3 Chest expansion (cm). United European Gastroenterol J. The primary objective of this study is to evaluate the efficacy of safety of etanercept dose reduction combined with sulfasalazine in ankylosing spondylitis (AS) patients who have achieved a significant … Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) >3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. WMD of change from baseline was 0.29 cm and 95% CI 0.15 to 0.44 cm. For MEDLINE (Ovid), the search strategy is in Appendix 1. The same reviewers independently entered the data extracted from the included trials, using RevMan double entry facility. WMD of change from baseline was ‐3.11 mm/hr and 95% CI ‐4.62 to ‐1.60 mm/hr. Comparison 1 SSZ vs placebo, Outcome 29 Spondylitis articular index (0‐90, the higher score the more severe disease). For other outcomes, however, no pooled data showed significant difference between intervention groups. Data extracted from the included trials were entered independently by JC and CL, using RevMan's double entry facility. Comparison 1 SSZ vs placebo, Outcome 25 Dactylitis score (0‐3, 0=normal, 3=severe). Comparison 1 SSZ vs placebo, Outcome 10 Reducing or stopping NSAIDs. Our site uses cookies to improve your experience. Pooled data of withdrawal for ineffectiveness showed no significant difference between intervention groups (Comparison 01.45). Comparison 1 SSZ vs placebo, Outcome 13 Forced vital volume (change from baseline) (L/min). Continuous data (eg visual analogue scales of pain) were entered as means and standard deviations (SD), and dichotomous outcomes (eg response, improvement) as number of events. Comparison 1 SSZ vs placebo, Outcome 43 CRP (2nd analysis) (ug/ml). The origins of heterogeneity, if present, were analyzed according to differences in methodological quality, characteristics of participants and intervention. But participants' characteristics were different (see Additional Table 01). NIH A grading of the evidence was performed using the grading system described in the 2004 book Evidence‐based Rheumatology (Tugwell 2004) and recommended by the Musculoskeletal Group: Platinum: A published systematic review that has at least two individual controlled trials each satisfying the following: Sample sizes of at least 50 per group ‐ if these do not find a statistically significant difference, they are adequately powered for a 20% relative difference in the relevant outcome. 2020 Nov 28;12:1759720X20975912. Arthritis Rheum. 1999 Nov;42(11):2325-9. doi: 10.1002/1529-0131(199911)42:11<2325::AID-ANR10>3.0.CO;2-C. Schmidt WA, Wierth S, Milleck D, Droste U, Gromnica-Ihle E. Z Rheumatol. Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 5 Fingers‐to‐floor test (cm). OBJECTIVE: Etanercept, a fully human tumor necrosis factor soluble receptor, is effective in treatment of ankylosing spondylitis (AS). Female participants accounted for 14%, much lower than that in the prevalence reported of 20‐35% (Sieper 2002b). I agree to these terms and conditions Download data, Copyright © 2000 - 2020 by John Wiley & Sons, Inc. All Rights Reserved Review our Privacy Policy, Search for your institution's name below to login via Shibboleth. This result, however, could not be confirmed by subsequent larger randomized clinical trials (Dougados 1995, Clegg 1996, Clegg 1999). Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. Can M, Aydın SZ, Niğdelioğlu A, Atagündüz P, Direskeneli H. Int J Rheum Dis. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. Standardized outcome measures are necessary to allow for comparison across trials. Handling of withdrawals >80% follow up (imputations based on methods such as Last Observation Carried Forward (LOCF) are acceptable). Sulfasalazine effectiveness for Ankylosing spondylitis … In 1990, Ferraz (Ferraz 1990) conducted a meta‐analysis of five randomized controlled trials involving 272 patients and concluded that sulfasalazine significantly relieved pain and morning stiffness, compared with placebo. Eleven trials treated a total of 895 patients, 469 receiving SSZ and 426 placebo. By continuing to browse this site you agree to us using cookies as described in About Cookies. Ankylosing spondylitis (type of arthritis affecting the spine) has been reported by people with ankylosing spondylitis, rheumatoid arthritis, pain, high blood pressure, osteoporosis. Morning stiffness decreased by 14 more points on a scale of 0 to 100 when taking sulfasalazine than fake pills. The data available are protected by copyright and may only be used in accordance with the Terms and Conditions. The pooled data showed that SSZ did significantly reduce ESR (even though the difference of 4.79 mm/hr does not have much clinical significance) and ease morning stiffness VAS‐100 mm. (2) SSZ management might be beneficial in patients with higher ESR (possibly > 30 mm/hr). In patients with peripheral arthritis (N = 15), no significant difference was found between intervention groups in back pain, score of sleep disturbance, chest expansion, Schober's test, fingers‐to‐floor test, articular index, degree of joint swelling, patient assessment of disease severity, duration of morning stiffness and ESR (Comparison 02). Conclusion: Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 2 Score of sleep disturbance (0‐4, 0=no disturbance, 4=severe disturbance). Sulfasalazine (SSZ) has been used in rheumatoid arthritis (RA) and AS for decades. 2002 Apr;61(2):159-67. doi: 10.1007/s003930200024. Is sulfasalazine effective in ankylosing spondylitis? This site needs JavaScript to work properly. Comparison 1 SSZ vs placebo, Outcome 31 Improvement in patient global assessement. Non‐steroidal anti‐inflammatory drugs (NSAIDs) are the main treatment for AS and can improve the symptoms of AS. See this image and copyright information in PMC. This Cochrane review provides the best evidence we have today. WMD of end point was ‐7.07 mm/hr and 95% CI ‐14.39 to 0.25 (insignificant statistically). Comparison 1 SSZ vs placebo, Outcome 4 Back pain (VAS‐100 mm, 0=no ppain, 100=severe). Ther Adv Musculoskelet Dis. Comparison 1 SSZ vs placebo, Outcome 44 withdrawal for side effect. For those refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Nothing was special about the intervention. Sulfasalazine (SSZ), a well-established disease-modifying antirheumatic drug (DMARD), is the only DMARD that is useful for any of the clinical manifestations of SpA, such as ankylosing … Comparison 1 SSZ vs placebo, Outcome 30 Spondylitis articular index (2nd analysis) (0‐90, the higher score the more severe disease). What is ankylosing spondylitis and why is sulfasalazine prescribed? Cochrane Database Syst Rev. The methodological quality of included trials was independently assessed by the same reviewers against the following criteria. Disease progression may result in loss of mobility and function. These studies included almost 900 people with ankylosing spondylitis, most of them were male and 27 to 46 years old. Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. The mean or median (depending on the trial) duration of disease was the shortest, with 5.7 years in SSZ and 3.8 years in placebo group (in other trials, it ranged from 8.4 to 21.9 years). Comparison 1 SSZ vs placebo, Outcome 16 Occiput‐to‐wall test (cm). For ESR, four trials (Clegg 1996, Krajnc 1990, Nissila 1988, Schmidt 2002) found statistically significant differences between intervention groups favouring SSZ over placebo. Comparison 1 SSZ vs placebo, Outcome 40 ESR (mm/hr). Sulfasalazine in undifferentiated spondyloarthropathies. These results showed that adverse effects of SSZ were obvious in some patients although the severe side effect was rare. Comparison 1 SSZ vs placebo, Outcome 42 CRP (ug/ml). A similar conclusion could be drawn from the DMARD management in RA where DMARD was recommended to be initiated within 3 months after diagnosis (ACR 2002). Three trials (Clegg 1996, Nissila 1988, Schmidt 2002) assessed CRP and only one (Schmidt 2002) showed significant difference between intervention groups, favouring SSZ over placebo. These findings, combined with the results of pooled data and the two most impressive trials (Clegg 1996, Kirwan 1993), could have important clinical implications: (1) SSZ management might be useful in early AS, possibly with the disease duration of less than 5 years. Select your preferred language for the Cochrane Library website. 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. Ward MM, Kuzis S "Medication toxicity among patients with ankylosing spondylitis." In Nissila 1988 trial, differences were significant in back pain VAS‐100 mm (WMD ‐12.00, 95% CI ‐23.10 to ‐0.90) (Comparison 01.04,05), chest expansion (WMD 1.00 cm, 95% CI 0.10 to 1.90 cm) (Comparison 01.411,12), occiput‐to‐wall test (WMD ‐0.80, 95% CI ‐1.55 to 0.05 cm) (Comparison 01.16,17), and patient's general well being VAS‐100 mm (WMD ‐11.00, 95% CI ‐19.84 to ‐2.16) (Comparison 01.33), favouring SSZ over placebo.  |  This has to be examined further by separately analysing patients with peripheral arthritis. Comparison 1 SSZ vs placebo, Outcome 7 Score of sleep disturbance (end point) (0‐4, 0=no disturbance, 4=severe disturbance). Comparison 1 SSZ vs placebo, Outcome 36 Duration of morning stiffness (hr). Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset. 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