2. Randomized controlled trials comparing sulphasalazine with placebo.

Study and Duration	Participants	Outcomes assessed	Results reported	Present analysis	ESR results	Spinal stiffness
Clegg 1996, 36 weeks	264 (SSZ: 31) (Placebo: 133) 29% with PA DD (year): 18.5±11.6 ESR (mm/h): 26.4±18.0 (SSZ) 25.2±22.0 (placebo)	Primary outcomes included response to treatment, improvement in PhGA, PGA, back pain and morning stiffness. Secondary outcomes included night pain (event), duration of morning stiffness, back pain VAS, spondylitis function index, joint/tenderness score, joint swelling score, dactylitis score, enthesopathy index, spondylitis articular index, chest expansion, Schober's test, occiput‐to‐wall test, fingers‐to‐floor test, ESR and CRP	Drop‐out: 19.3%. Both end point value and change from baseline were presented for all continuous outcomes. No difference was found between treatment groups in all outcomes except ESR, which declined more with SSZ than placebo group (P < 0.0001). When comparing SSZ responders with non‐responders, the former had a greater decrease in ESR (P < 0.04). Subgroup analysis showed that in patients with PA, 55.9% of SSZ group and 30.2% of placebo group got peripheral response (P = 0.023)	All the results reported have been confirmed except subgroup analysis where no information about treatment allocation was available for analysis. MD for ESR (change from baseline) was ‐3.10 mm/h, 95% CI ‐4.85 to ‐1.35 mm/h, favoring SSZ group	Absolute benefit from SSZ: ‐3.6 mm/h Relative difference in change from baseline: ‐14%	Did not report
Corkill 1990, 48 weeks	62 (SSZ: 32) (Placebo: 30) 19% with PA DD (year): 12.3±8.2 (SSZ) 16.1±11.4 (placebo) ESR (mm/h): 15±16 (SSZ) 24±26 (placebo)	Spinal pain VAS, spinal stiffness VAS, peripheral joint pain VAS, Schober's test, chest expansion, cervical flexion, cervical rotation, and ESR	Drop‐out: 1.6%. No significant difference was found between treatment groups	Because SDs were not given for all outcomes, these results could not be analyzed	Absolute benefit from SSZ: ‐0.1 mm/h Relative difference in change from baseline: ‐1%	Absolute benefit from SSZ: ‐9.8 mm on 100 mm VAS Relative difference in change from baseline: ‐25%
Davis 1989, 3 months	30 (SSZ: 15) (Placebo: 15) 23% with PA DD (year): 8.6 (SSZ) 8.4 (placebo) ESR (mm/h): 24±7.8 (SSZ) 26.4±8.6 (placebo)	Pain VAS, spinal stiffness VAS, sleep disturbance (event), occiput‐to‐wall test, fingers‐to‐floor test, ESR and CRP	Drop‐out: 6.7%. In SSZ group, all clinical outcomes showed significantly improved when initial and 3 months results are compared	Pain VAS, spinal stiffness VAS and CRP could not be analyzed because means and SDs were not given. No significant difference was found in any other outcome	Absolute benefit from SSZ: ‐5.4 mm/h Relatiive difference in change from baseline: ‐20%	Absolute benefit from SSZ: ‐20 mm on 100 mm VAS Relative difference in change from baseline: ‐40%
Dougados 1986, 6 months	60 (SSZ: 30) (Placebo: 30) None with PA DD (year, median): 10 ESR (mm/h, median): 13.5 (SSZ) 11.0 (placebo)	PGA, score of daily NSAIDs, pain VAS, joint index, frequency of nocturnal awakening, function index, Schober's test, fingers‐to‐floor test, chest expansion and ESR	Drop‐out: 21.7%. Success in PGA was more in SSZ than in placebo group (15/30 vs 6/30, P < 0.05). SSZ resulted in a significant reduction in score of daily NSAIDs (P < 0.05) and significant improvement of function index (P was not given) compared with placebo. No significant difference was found in other outcomes	All continuous outcomes were presented as median and 95% CI. For RevMan analysis, we assumed that mean is equal to median for each outcome and calculated SD from 95% CI and sample size. Success in PGA was more in SSZ than in placebo group (RR 2.5, 95% CI 1.12 to 5.56). No significant difference was found between treatment groups in other outcomes	Absolute benefit from SSZ: 0 mm/h	Did not report
Feltelius 1986, 12 weeks	37 (SSZ:18) (Placebo: 19) 5% with PA DD (year, median): 12.1 (SSZ) 10.4 (placebo) ESR (mm/h): 24.3±17.4 (SSZ) 28.5±19.5 (placebo)	Duration of morning stiffness, spinal stiffness VAS, pain VAS, general wellbeing VAS, chest expansion, Schober's test, sleep disturbance (event), sacroiliac pain VAS, ESR	Drop‐out: 21.6%. Spinal stiffness VAS, chest expansion and sleep disturbance were significantly improved in SSZ compared with placebo group	All outcomes were presented as graphs and no data were available for analysis except ESR that showed no significant difference between treatment groups	Absolute benefit from SSZ: 1.3 mm/h Relative difference in change from baseline: 5%	Did not report
Kirwan 1993, 3 years	89 (SSZ: 44) (Placebo: 45) 28% with PA DD (year): 19±12 (SSZ) 21.9±11.7 (placebo) ESR not given	Primary outcomes included Schober's test, chest expansion, and lateral cervical flexion. Secondary outcomes included function (HAQ), back pain VAS, consumption of anti‐inflammatory drugs, sleep disturbance VAS, PGA, episodes of peripheral arthritis, episodes of heel pain, flares in general AS symptoms, episodes of arthritis	Drop‐out: 30.3%. No significant difference was found between treatment groups in all outcomes except occurrence of peripheral joint symptoms. The episodes of PA were 0.289 episodes/year in SSZ and 0.392 episodes/year in placebo group, respectively (P < 0.05)	There were significantly more drop‐outs for any reason in SSZ than in placebo group. RR was 2.43 (95% CI 1.19 to 4.96). No data were available for analysis in any other outcome	Did not report	Did not report
Krajnc 1990, 24 weeks	95 (SSZ: 71) (Placebo: 24) 66% with PA DD not given ESR (mm/h): 41±19 (SSZ) 43±18 (placebo)	Duration of morning stiffness, Schober's test, chest expansion, fingers‐to‐floor test, number of painful/swollen joints and ESR	Drop‐out: 14.3%. In SSZ group, duration of morning stiffness, chest expansion, number of painful/swollen joints and ESR showed significantly improved when initial and 24 weeks results are compared	No significant difference was found between treatment groups in all outcomes except ESR (MD ‐17.00 mm/h, 95% CI ‐26.99 to ‐7.01mm/h, favoring SSZ)	Absolute benefit from SSZ: 15 mm/h Relatiive difference in change from baseline: ‐35%	Absoluete benefit from SSZ: ‐4 mm on 100 mm VAS Relative difference in change from baseline: ‐8%
Nissila 1988, 26 weeks	85 (SSZ: 43 (Placebo: 42) 68% with PA DD (year): 5.4±7.3 (SSZ) 3.8±4.3 (placebo) ESR (mm/h): 42±20 (SSZ) 46±19 (placebo)	Duration of morning stiffness, spinal stiffness VAS, chest expansion, Schober's test, fingers‐to‐floor test, occiput‐to‐wall test, number of painful joints, number of swollen joints, general wellbeing VAS, ESR and CRP	Drop‐out: 12.2%. Significant differences between treatment groups were found in morning stiffness VAS (P = 0.02), chest expansion (P = 0.03) and ESR (P = 0.02), favoring SSZ. No significant difference was found in other outcomes. Note: we suspected that results of chest expansion were errors because they were impossible to be about 40 to 50 cm. So we divided them by 10 for analysis	Significant differences were found in morning stiffness VAS 100 mm (0 = no stiffness, 100 = severe, MD ‐14.00, 95% CI ‐23.78 to ‐4.22), chest expansion (MD 1.00 cm, 95% CI 0.10 to 1.90 cm), occiput‐to‐wall test (MD ‐0.80 cm, 95% CI ‐1.55 to 0.05 cm), ESR (MD ‐19.00 mm/h, 95% CI ‐29.65 to ‐8.35 mm/h), and general wellbeing VAS 100 mm (0 = the best, 100 = the worst, MD ‐11.00, 95% CI ‐19.84 to ‐2.16), favoring SSZ. No significant difference was found in other outcomes	Absolute benefit from SSZ: ‐15 mm/h Relatiive difference in change from baseline: ‐33%	Absolute benefit from SSZ: ‐6 mm on 100 mm VAS Relative difference in change from baseline: ‐15%
Schmidt 2002, 26 weeks	70 (SSZ: 34) (Placebo: 36) 36% with PA DD (year): 16.7±7.2 (SSZ) 16.3±7.8 (placebo) ESR (mm/h): 23.1±3.2 (SSZ) 20.4±2.4 (placebo)	Back pain VAS, nocturnal awakening (event), pain/tenderness score, duration of morning stiffness, number of painful joints, number of swollen joints, spondylitis function index, PGA, PhGA, Schober's test, fingers‐to‐floor test, chin sternum distance, chest expansion, ESR and CRP	Drop‐out: 36%. No significant difference was reported between treatment groups. There were more drop‐outs in SSZ than in placebo (38% vs 11%)	All continuous outcomes were analyzed as change from baseline. Significant differences were found between treatment groups in back pain VAS 100 mm (0 = no pain, 100 = severe pain, MD ‐2.30, 95% CI ‐4.44 to ‐0.16), chest expansion (MD 0.30 cm, 95% CI 0.16 to 0.44 cm), Schober's test (MD 0.50 cm, 95 CI 0.44 to 0.56 cm), duration of morning stiffness (MD ‐0.39 h, 95% CI ‐0.48 to ‐0.30 h), ESR (MD ‐3.10 mm/h, 95% CI ‐4.85 to ‐1.35 mm/h) and CRP (MD ‐2.50 µg/ml, 95% CI ‐4.70 to ‐0.30 µg/ml), favoring SSZ group. But in occiput‐to‐wall test, the difference (MD 0.70 cm, 95% CI 0.32 to 1.08 cm) favored placebo over SSZ. No significant difference was found in other outcomes. There were significantly more withdrawals for side effects and drop‐outs for any reason in SSZ than in placebo group. RRs were 3.44 (95% CI 1.24 to 9.52) and 2.42 (95% CI 1.14 to 5.15), respectively	Absolute benefit from SSZ: ‐3.1 mm/h Relatiive difference in change from baseline: ‐15%	Did not report
Taylor 1991, 1 year	40 (SSZ: 20) (Placebo: 20) 15% with PA DD (year): 11±1.6 (SSZ) 10.7±1.6 (placebo) ESR (mm/h, mean): 27 (SSZ) 25 (placebo)	Back pain VAS, fingers‐to‐floor test, chest expansion, sleep disturbance (event), forced vital volume, occiput‐to‐wall test, Schober's test, spinal stiffness VAS, reduction or stop of NSAIDs (event)	Drop‐out: 17.5%. No significant difference was found between treatment groups in all outcomes except pain VAS (P < 0.05, favoring SSZ)	No significant difference was found between treatment groups in all outcomes including pain VAS	Did not report	Absolute benefit from SSZ: ‐13.5 mm on 100 mm VAS Relative difference in change from baseline: ‐42%
Winkler 1989, 24 weeks	63 (SSZ: 31) (Placebo: 32) 33% with PA DD (year, median): 10.8 (SSZ) 11.2 (placebo) ESR (mm/h): 33.4±20.4 (SSZ) 26.9±16.4 (placebo)	ESR, duration of morning stiffness, back pain VAS, score of sleep disturbance, chest expansion, Schober's test, fingers‐to‐floor test, disease severity in PGA	Drop‐out: 22.2%. The advantage of SSZ over placebo was significant only in the duration of morning stiffness (P < 0.05) and score of sleep disturbance (P< 0.05). In subgroup analysis, the same results were found in patients with axial form (N = 34). In patients with peripheral arthritis (N = 15), articular index showed significant improvement in SSZ over placebo (P < 0.05)	No significant difference was found between treatment groups in all outcomes. In subgroup analysis of patients with axial form, we found significant difference favoring SSZ over placebo in back pain VAS 100 mm (0 = no pain, 100 = severe pain). MD was ‐9.20 and 95% CI ‐17.81 to 0.59	Absolute benefit from SSZ: ‐2.7 mm/h Relatiive difference in change from baseline: ‐10%	Did not report

CI ‐ confidence interval
 CRP ‐ C‐reactive protein
 DD ‐ duration of disease
 ESR ‐ erythrocyte sedimentation rate
 HAQ ‐ health assessment questionnaire
 MD ‐ mean difference
 mm/hr ‐ millimetre per hour
 NSAIDs ‐ non‐steroidal anti‐inflammatory drugs
 PA ‐ peripheral arthritis
 PGA ‐ patient global assessment
 PhGA ‐ physician global assessment
 RR ‐ relative risk
 SD ‐ standard deviation
 SSZ ‐ sulphasalazine
 VAS ‐ visual analogue scale