Comparison 1 SSZ vs placebo, Outcome 37 Duration of morning stiffness (2nd analysis) (hr). You will see translated Review sections in your preferred language. These studies included almost 900 people with ankylosing spondylitis, most of them were male and 27 to 46 years old. 1,2. Conventional disease-modifying antirheumatic drugs therapy may not slow spinal radiographic progression in ankylosing spondylitis: results from an 18-year longitudinal dataset. In the present review, only one trial (Winkler 1989) gave the separate data of patients with peripheral arthritis but the sample size was small (N = 15). It is the best studied DMARD used in AS, but its efficacy remains unclear. Seven of them (Clegg 1999, Dougados 1987, Dougados 1990, Nissila 1994, Reda 1995, Schmidt 2000, Taggart 1995) were duplicate publications. When deselected, the pooled difference of ESR (end point) became statistically significant (WMD ‐6.13 mm/hr, 95% CI ‐11.89 to ‐0.37 mm/hr) while other results remained similar. But severe side effects appear rare. Patients with ankylosing spondylitis fulfilling one of the following and other criteria: 1961 Rome, 1966 New York, modified 1984 New York, Amor or ESSG (European Spondyloarthropathy Study Group) criteria (Olivieri 2002). Data extracted from the included trials were entered independently by JC and CL, using RevMan's double entry facility. A systematic review of randomized controlled trials. WMD of change from baseline was 0.29 cm and 95% CI 0.15 to 0.44 cm. Arthritis Rheum. Potential trials for inclusion were identified from the search results. COVID-19 is an emerging, rapidly evolving situation. Sulfasalazine effectiveness for Ankylosing spondylitis … Time to event data were also used to describe peripheral joint symptoms in Kirwan 1993. Clinical efficacy of etanercept versus sulfasalazine in ankylosing spondylitis subjects with peripheral joint … None of these studies used ASAS improvement criteria for AS (Anderson 2001, Brandt 2004), simply because all these studies were conducted before the criteria were published. No significant difference was found in other parameters. doi: 10.1002/14651858.CD004800.pub2. The pooled result showed no significant difference (Comparison 01.42,43). Finally, in order to explain why SSZ demonstrated benefit in Nissila 1988 but not in other studies, we looked into this study to see if it was different from other studies. The origins of heterogeneity, if present, were analyzed according to differences in methodological quality, characteristics of participants and intervention. Select your preferred language for the Cochrane Library website. Again when Schmidt 2002 trial was deselected, the heterogeneity became insignificant. Comparison 1 SSZ vs placebo, Outcome 28 Enthesopathy index (2nd analysis) (0‐90, 0‐66, 0‐90? Comparison 1 SSZ vs placebo, Outcome 10 Reducing or stopping NSAIDs. Comparison 1 SSZ vs placebo, Outcome 43 CRP (2nd analysis) (ug/ml). People had side effects such as stomach upset, skin reactions/rashes and mouth sores. 3. 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 5 Back pain (2nd analysis) (VAS‐100mm, 0=no pain, 100=severe). This could be due to the large difference of ESR at baseline levels among the studies (Additional Table 01). 3. Is sulfasalazine effective in ankylosing spondylitis? doi: 10.1177/1759720X20975912. (see Additional Table 01). We thought that imbalance in treatment allocation (71 in SSZ and 24 in placebo group) could be the reason for the observed negative results in Krajnc 1990 trial. Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 6 Patient assessment of disease severity (VAS‐100mm, 0=very good, 100=very poor). Comparison 1 SSZ vs placebo, Outcome 12 Chest expansion (2nd analysis) (cm). The primary outcome variable was the change in BASDAI over 6 months. Pooled data showed a similar result. Sulfasalazine is a disease‐modifying antirheumatic drug used in the treatment of AS. 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. Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 1 Back pain (VAS‐100mm, 0 as no pain, 100 severe). Comparison 1 SSZ vs placebo, Outcome 29 Spondylitis articular index (0‐90, the higher score the more severe disease). Lee TH, Koo BS, Nam B, Oh JS, Park SY, Lee S, Joo KB, Kim TH. Comparison 1 SSZ vs placebo, Outcome 24 Joint swelling score (2nd analysis) (0‐198, the higher score the more severe disease). The other 11 trials (Clegg 1996, Corkill 1990, Davis 1989, Dougados 1986, Feltelius 1986, Kirwan 1993, Krajnc 1990, Nissila 1988, Schmidt 2002, Taylor 1991, Winkler 1989) compared SSZ with placebo. Comparison 2 SSZ vs placebo (AS with peripheral arthritis, end point values), Outcome 7 Degree of joint swelling (0‐66, the higher score the more severe disease). More people stopped taking sulfasalazine because of the side effects than when taking fake pills. 2020 Nov;8(9):1031-1044. doi: 10.1177/2050640620958902. Clegg et al (Clegg 1996) conduct the trial with the largest sample size of 264 (there were less than 100 in all other trials) and treatment duration of 36 weeks. For ESR, four trials (Clegg 1996, Krajnc 1990, Nissila 1988, Schmidt 2002) found statistically significant differences between intervention groups favouring SSZ over placebo. Five studies (Davis 1989, Dougados 1986, Feltelius 1986, Krajnc 1990, Nissila 1988) reported that SSZ was beneficial. Continuous data of Dougados 1986 presented in the present review were assumed and calculated from the original paper and possibly inaccurate. After deselection of Schmidt 2002 (no continuous data was available in Kirwan 1993), we found that WMD of chest expansion and WMD of duration morning stiffness (change from baseline) became insignificant, which have been mentioned above. In the present review, all trials selected patients with active disease but the definition was quite different among the trials. We evaluated randomised and quasi‐randomised trials examining the efficacy of sulfasalazine on ankylosing spondylitis. 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. Loss and gain of bone in spondyloarthritis: what drives these opposing clinical features? Disease progression may result in loss of mobility and function. Curr Rheumatol Rep. 2007 Oct;9(5):349-50. But when NSAIDs are not working well disease modifying anti‐rheumatic drugs (DMARDs), such as sulfasalazine may be used. Comparison 2 SSZ vs placebo (AS with peripheral arthritis, end point values), Outcome 1 Back pain (VAS‐100mm, 0=no pain, 100=severe). These medications have been shown to be highly effective in treating not only the arthritis of the joints, but also the inflammation in the gut and eyes, as well as the spinal arthritis associated with ankylosing spondylitis … No noticeable difference in treatment was observed between groups. The duration of treatment ranged from 12 weeks to 3 years. But the difference of pooled results was statistically insignificant (Comparison 01.36,37). Aim: To evaluate efficacy of sulfasalazine for axial ankylosing spondylosis. 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 … Comparison 1 SSZ vs placebo, Outcome 31 Improvement in patient global assessement. Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 7 Duration of morning stiffness (hr). Comparison 1 SSZ vs placebo, Outcome 7 Score of sleep disturbance (end point) (0‐4, 0=no disturbance, 4=severe disturbance). Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised … The outcomes in continuous data were presented as either end point values or change from baseline or both. Peripheral joints/entheses were assessed in several studies (Clegg 1996, Dougados 1986, Kirwan 1993, Nissila 1988, Schmidt 2002). Methods: As for methodological quality, all trials included in the present reviews were rated as A or B in both concealment and blinding assessment, but proportion of drop‐out differed among the trials. 2020 Jun;7(2):415-423. doi: 10.1007/s40744-020-00208-5. Patients at early disease stage, with higher level of ESR (or active disease) and peripheral arthritis might benefit from SSZ. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. United European Gastroenterol J. Nissila 1988 is the only trial in which SSZ showed benefit in primary outcome analyses, including back pain, chest expansion, occiput‐to‐wall test and patient's general well being. There was significant heterogeneity among the trials (p<0.0001) ((Comparison 01.12). Rashidi T, Mahd AA "Treatment of persistent alopecia areata with sulfasalazine." Only one study (Winkler 1989) presented data of subgroups (patients with and without peripheral arthritis). Introduction. For allocation concealment, we scored as A (adequate), B (unclear), C (inadequate) and D (not used). Spondylitis Association of America (SAA) is a national, non-profit organization, dedicated to being a leader in the quest to cure ankylosing spondylitis and related diseases, and to empower those affected to live life to the fullest. Comparison 1 SSZ vs placebo, Outcome 46 Drop‐out for any reason. Comparison 1 SSZ vs placebo, Outcome 30 Spondylitis articular index (2nd analysis) (0‐90, the higher score the more severe disease). Conclusion: The herb-separated … Kirwan 1993 trial lasted 3 years (all other trials lasted not more than 1 year) and included 89 participants. Comparison 1 SSZ vs placebo, Outcome 17 Occiput‐to‐wall test (2nd analysis) (cm). Conventional DMARD therapy (methotrexate-sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: a real-life experience. Sulfasalazine reduces spinal stiffness, peripheral arthritis, and the erythrocyte sedimentation rate (ESR), but there is no evidence that it improves spinal mobility, enthesitis, or … This has to be examined further by separately analysing patients with peripheral arthritis. the higher score the more severe disease) Show forest plot, 28 Enthesopathy index (2nd analysis) (0‐90, 0‐66, 0‐90? The methodological quality of included trials was independently assessed by the same reviewers against the following criteria. Most trials presented the data of AS patients as a whole in which some outcomes, for example, score and number of painful joints, score and number of swollen joints were insensitive to change because patients without peripheral arthritis would be definitely recorded as zero. In the present review, we added six other trials and increased the number of participant to 895. Treatment recommendations for AS recommend against using sulfasalazine to manage AS, as there is little to no evidence for its effectiveness … Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial. Comparison 1 SSZ vs placebo, Outcome 33 General well‐being (end point) (VAS‐100mm, 0=very good, 100=very poor). Here peripheral response was composition of 4 parameters, eg patient self‐assessment, physician assessment, joint pain/tenderness score and joint swelling score. Comparison 1 SSZ vs placebo, Outcome 26 Dactylitis score (2nd analysis) (0‐3, 0=normal, 3=severe). 2005 Apr 18;(2):CD004800. Comparison 1 SSZ vs placebo, Outcome 2 Spondylitis function index (2nd analysis) (score 0‐40, 0‐44, 0=the best, the more the worse). Comparison 1 SSZ vs placebo, Outcome 18 Fingers‐to‐floor test (cm). TNF inhibitors (eg, infliximab, etanercept, adalimumab, certolizumab, golimumab) In a study of adult patients with recent-onset peripheral spondyloarthritis (symptom … In the present analysis, the effectiveness of SSZ was confirmed only in Nissila 1988 study where severity of pain, chest expansion, patient general well‐being, morning stiffness and ESR were significantly improved although more success of treatment (judged by patients) was also confirmed in Dougados 1986 study. Comparison 2 SSZ vs placebo (AS with peripheral arthritis, end point values), Outcome 5 Fingers‐to‐floor test (cm). The total effective rate was 90.0% (27/30) in the herb-separated moxibustion group, which was higher than 73.3% (22/30) in the conventional moxibustion group ( P <0.05). Comparison 1 SSZ vs placebo, Outcome 45 Withdrawal for ineffectiveness. Epub 2020 Apr 23. Comparison 1 SSZ vs placebo, Outcome 35 Respond to treatment (based on both patient and physician assessment). One study (Benitez‐Del‐Castillo) did not assess relevant outcomes for the present review. Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Version published: 20 April 2005 Version history. Results: 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. All the dichotomous data presented in Table comparisons and data were according to intention‐to‐treat analysis. 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. There is "gold" level of evidence that sulfasalazine improves morning stiffness and the erythrocyte sedimentation rate (ESR) in people with ankylosing spondylitis. Select your preferred language for Cochrane Reviews. Comparison 1 SSZ vs placebo, Outcome 40 ESR (mm/hr). | 4. It can come and go, last for long periods, and be quite severe. Silver ranking would also include evidence from at least one study of non‐randomised cohorts that did and did not receive the therapy, or evidence from at least one high quality case‐control study. Several studies presented their results in a form that did not allow analysis in RevMan. 9 out of 100 people stopped taking fake pills. USA.gov. WMD of change from baseline was ‐3.11 mm/hr and 95% CI ‐4.62 to ‐1.60 mm/hr. However, we did not analyze this outcome because the information on the numbers of participants allocated to treatment and control groups was not given. For other criteria, we scored as A (yes), B (unclear) and C (no). Nothing was special about the intervention. Comparison 1 SSZ vs placebo, Outcome 14 (Modified) Schober's test (cm). These results showed that adverse effects of SSZ were obvious in some patients although the severe side effect was rare. Higher ESR indicates active disease but the definition of active disease is equivocal so far. (3) SSZ might be beneficial in patients with peripheral arthritis. Only one trial (Krajnc 1990) could match Nissila 1988 in these aspects (duration of disease was not given, baseline ESR was 41 for SSZ and 43 for placebo group, patients with peripheral arthritis took up 66%). Can M, Aydın SZ, Niğdelioğlu A, Atagündüz P, Direskeneli H. Int J Rheum Dis. WMD was ‐13.89 and 95% CI ‐22.54 to ‐5.24 (Comparison 01.38). 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). Unblinded trial reports were reviewed independently by JC and CL according to the selection criteria. Sensitivity analysis, however, found no obvious difference between selection and deselection of this trial in the pooled result. Sensitivity analysis We did not conduct sensitivity analysis for concealment and blind assessment because all trials were rated as A or B. Clegg 1996 was one of them. Secondary outcomes included measures of spinal pain, physical function and inflammation. First, we examined those trials with high methodological quality, larger sample size and longer period of treatment. In the Clegg 1996 study, the only presented outcome was response rate, which summarized patient self‐assessment, physician assessment, back pain, duration of morning stiffness, joint pain/tenderness score (for patients with peripheral arthritis) and joint swelling score (for patients with peripheral arthritis). However, its efficacy remains unclear. Bronze: The bronze ranking is given to evidence if at least one high quality case series without controls (including simple before/after studies in which patients act as their own control) or if the conclusion is derived from expert opinion based on clinical experience without reference to any of the foregoing (for example, argument from physiology, bench research or first principles). Comparison 3 SSZ vs placebo (axial form AS, end point values), Outcome 4 Schober's test (cm). 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. The pooled analysis showed that the difference between intervention groups was significant only in erythrocyte sedimentation rate (ESR) (WMD ‐4.79, 95% CI ‐8.80 to ‐0.78) mm/h) and morning stiffness VAS‐100 mm (visual analogue scale 100 mm, where 0 = no stiffness and 100 = severe) (WMD ‐13.89, 95% CI ‐22.54 to ‐5.24), favouring SSZ over placebo. Methods: 67 patients fulfilling the inclusion criteria were included and randomized into treatment and placebo group. Primary outcomes Three trials (Dougados 1986, Nissila 1988, Schmidt 2002) showed statistically significant differences between treatment groups (Additional Table 01). Studies with spondyloarthropathies/spondyloarthritis patients as participants were included if there were available data assessing the outcomes specific to patients with AS. In five studies (Burgos‐Vargas 2002a, Burgos‐Vargas 2002b, Dekeyser 1995, Dougados 1995, Lehtinen 1995), participants were patients with spondyloarthropathy and the outcomes specific for AS patients were not given separately. For other outcomes, however, no pooled data showed significant difference between intervention groups. [Sulfasalazine in ankylosing spondylitis: a prospective, randomized, double-blind placebo-controlled study and comparison with other controlled studies]. 2020 Nov 28;12:1759720X20975912. 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