Wanders 2005.

Methods	Design: RCT Number of centres: 76 Treatment duration: 2 years Flare design: Yes Wash‐out period: Yes (2 to 14 days, Paracetamol only) Time point of assessments: BL, 1, 4, 7, 10, 13, 16, 22, 24 months
Participants	Inclusion criteria: 1. Daily NSAID intake during the month preceding the screening visit; 2. An NSAID washout period of 2 to 14 days before the BL visit; 3. A flare of the disease at BL, defined by absolute score for pain of ≥ 40 mm (100 mm VAS) and increase in pain of at least 30% between screening visit and BL visit. Exclusion criteria: 1. Patients with peripheral arthritis (presence of active synovitis with swelling of a peripheral joint at the screening visit; 2. Active inflammatory bowel disease; 3. Patients with severe concomitant medical illness; 4. Received corticosteroids in previous 6 weeks before start of the study; 5. Any DMARD with a change in dosage during previous 6 months; 6. Confirmed peptic ulcer by gastro‐duodenoscopy within the year preceding screening visit. Classification: modified New York criteria Celecoxib (400 mg) continuous: Number of participants: 111 Number of completers: 96 (68 completed the study while taking celecoxib, 28 patients completed the study while taking a different NSAID) Age (mean (SD)): 38.0 (10.7) Male (%): 67 Symptom duration: NA Disease duration (mean (SD)): 11.9 (9.3) years HLA‐B27 positive (%): 86 Celecoxib (400 mg) on‐demand: Number of participants: 103 Number of completers: 86 (67 completed the study while taking celecoxib, 19 patients completed the study while taking a different NSAID) Age (mean (SD)): 40.1 (10.5) Male (%): 72 Symptom duration: NA Disease duration (mean (SD)): 11.0 (9.4) years HLA‐B27 positive (%): 87
Interventions	Celecoxib (400 mg) continuous vs Celecoxib (400 mg) on‐demand Co‐medication: Analgesics or DMARDs without changing dosage, or both.
Outcomes	Extracted outcomes: 1. Pain on VAS (BL (± SD), post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 50 ± 38, 36.41 ± 30.40 Celecoxib on‐demand: 54 ± 37, 39.05 ± 29.99 2. Withdrawals due to adverse events (post‐treatment after 2 years) Celecoxib continuous: n = 2 (total N = 111) Celecoxib on‐demand: n = 3 (total N = 103) 3. BASDAI (BL not available, post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 28.88 ± 21.03 Celecoxib on‐demand: 32.40 ± 22.59 4. Patient's global assessment of disease activity (BL (± SD), post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 43 ± 29, 34.73 ± 28.70 Celecoxib on‐demand: 47 ± 31, 40.05 ± 28.01 5. Fatigue (BL not available, post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 37.54 ± 27.21 Celecoxib on‐demand: 37.75 ± 27.42 6. Duration of morning stiffness (BL not available, post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 38.37 ± 52.48 Celecoxib on‐demand: 38.01 ± 46.65 7. Severity of morning stiffness (BL not available, post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 27.51 ± 22.92 Celecoxib on‐demand: 33.07 ± 25.15 8. CRP (BL (± SD)), post‐treatment after 2 years (± SD)) (in mg/L, higher is worse) Celecoxib continuous: 14.7 ± 17.9, 12.56 ± 13.88 Celecoxib on‐demand: 12.7 ± 17.1, 11.98 ± 17.20 9. ESR (BL (± SD)), post‐treatment after 2 years (± SD)) (in mm/hr, higher is worse) Celecoxib continuous: 17.0 ± 13.8, 14.22 ± 12.11 Celecoxib on‐demand: 17.0 ± 16.7, 15.96 ± 14.49 10. BASFI (BL (± SD), post‐treatment after 2 years (± SD)) (scale 0 to 100, higher is worse) Celecoxib continuous: 33 ± 25, 28.49 ± 23.01 Celecoxib on‐demand: 38 ± 28, 31.76 ± 25.49 11. Chest expansion (BL (± SD), post‐treatment after 2 years (± SD)) (in cm, higher is better) Celecoxib continuous: 4.7 ± 2.3, 5.17 ± 2.49 Celecoxib on‐demand: 5.0 ± 2.3, 5.39 ± 2.20 12. Occiput‐to‐wall distance (BL not available, post‐treatment after 2 years (± SD)) (in cm, higher is worse) Celecoxib continuous: 3.56 ± 4.86 Celecoxib on‐demand: 2.63 ± 3.55 13. Schober's test (BL (± SD), post‐treatment after 2 years (± SD)) (in cm, higher is better) Celecoxib continuous: 3.2 ± 1.4, 3.10 ± 1.47 Celecoxib on‐demand: 3.2 ± 1.4, 3.19 ± 1.37 14. mSASSS (BL (± SD), post‐treatment after 2 years (± SD)) (in cm, higher is worse, n = only patients with a X‐ray) Celecoxib continuous: 7.9 ± 14.7 (N = 76), 8.28 ± 14.72 (N = 76) Celecoxib on‐demand: 9.3 ± 15.2 (N = 74), 10.75 ± 16.15 (N = 74) 15. Number of patients with at least 2 mSASSS units radiographic progression (post‐treatment after 2 years) (n = only patients with a X‐ray) Celecoxib continuous: n = 12 (total N = 76) Celecoxib on‐demand: n = 26 (total N = 74) 16. Number of serious adverse events (post‐treatment after 2 years) Celecoxib continuous: n = 22 (total N = 111) Celecoxib on‐demand: n = 16 (total N = 103) 17. Number of adverse events per organ system (post‐treatment after 2 years) Celecoxib continuous: cardiovascular 14, gastro‐intestinal 102, hepatic 3, respiratory 59, haematological 1, renal 1, neurologic 20, dermatological 14 (total N = 111) Celecoxib on‐demand: cardiovascular 11, gastro‐intestinal 75, hepatic 0, respiratory 61, haematological 3, renal 0, neurologic 18, dermatological 14 (total N = 103)
Notes	Not included in the meta‐analysis, because the study was not suitable for any of the comparisons in this review. Available results are reported in this table. A post‐hoc analysis of this study was also included in the review (Kroon 2012), for detailed description see Table 4. Funding source: Supported by an unrestricted grant from Pharmacia.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Randomization was performed using a computer‐generated randomization list".
Allocation concealment (selection bias)	Unclear risk	No information provided on allocation concealment.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants were not blinded because the treatment regimens differed. However, it questionable whether this introduced bias.
Blinding of outcome assessment (detection bias) All outcomes	High risk	Only mSASSS scoring was blinded. Other outcomes were assessed by self‐report.
Incomplete outcome data (attrition bias) All outcomes	Low risk	"Missing values for variables assessing signs and symptoms were replaced by the last observation that was present, which was carried forward, provided that at least one value obtained while the patient was receiving treatment was available." "...imputation of missing data by different means did not influence the direction of the between‐group difference..." 86% in continuous treatment and 83% in on‐demand treatment completed trial. For radiographic progression only patients with a complete set of radiographs were used. The BL characteristics did not differ, indicating a non‐selective group of participants.
Selective reporting (reporting bias)	Low risk	All outcomes stated in the methods were reported.
Other bias	Low risk	Compliance with treatment regimen was high. No other biases were detected.

Abbreviations: APAP = acetaminophen; ARA = American Rheumatism Association; AS = ankylosing spondylitis; ASAS = Assessment of SpondyloArthritis international Society; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BASFI = Bath Ankylosing Spondylitis Functional Index; BASMI = Bath Ankylosing Spondylitis Metrology Index; BL = baseline; CCT = controlled clinical trial; CI = confidence interval; cm = centimetre; CNS = central nervous system; COX = cyclo‐oxygenase; CRP = C‐reactive protein; ESR = erythrocyte sedimentation rate; ESSG = European Spondylarthropathy Study Group; GI = gastrointestinal; HLA = human like antigen; mg = milligram; mm = millimetre; MTX = methotrexate; NA = not available; NSAID = non‐steroidal antiinflammatory drug; RCT = randomised controlled trial; SD = standard deviation; SE = standard error; SpA = spondylarthritis; SSZ = sulfasalazine; TNF = tumour necrosis factor; VAS = visual analogue scale; WBC = white blood cell count.