Heydendael 2003

Methods	RCT, active‐controlled, open‐label trial Date of study: October 1998‐June 2000 Location: multicentre (> 1) in Amsterdam/the Netherlands
Participants	Randomised: 88 participants, mean age 40 years, 57 male Inclusion criteria Participants with moderate‐severe psoriasis, PASI>8, Age ≥18 Non‐response to topical treatment Non‐response to phototherapy Number of allowed previous treatment line: 2 Exclusion criteria Pregnancy, kidney insufficiency, liver insufficiency, high‐risk liver function abnormalities, hepatitis B Had received methotrexate or ciclosporin Had an active infection Had uncontrolled diabetes (Insulino dependent) Had uncontrolled cardiovascular disorder Had uncontrolled hypertension Had past history of malignant tumours Dropouts and withdrawals 3/88 (3.4%) Methotrexate group (1): withdrew consent (1) Ciclosporin group (2): ineligible (2)
Interventions	Intervention A. Methotrexate (n = 44), orally, 15 mg/week until 4 weeks then increase up to 22.5 mg if reduction from baseline PASI < 25%, 3 divided doses with 12‐h interval, 12 weeks Control intervention B. Ciclosporin (n = 44), orally, 3 mg/kg until 4 weeks then increase up to 5 mg/kg if reduction from baseline PASI < 25%, 2 divided doses, 12 weeks
Outcomes	Assessments at weeks 16 weeks Primary outcomes of the trial PASI Secondary outcomes of the trial Side effects SF36
Notes	Funding sources, quote (p 664): "Supported by a grant (OG 97‐009) from the Dutch Health Authorities" Declarations of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 660): "Randomisation was performed centrally with the use of computer‐generated random numbers and block size of eight patients" Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (p 660): "Randomisation was performed centrally with the use of computer‐generated random numbers and block size of eight patients" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Comment: no blinding
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote (p 660): "The score of the PASI ... was determined... by trained assessors who were unaware of the treatment assignment" Comment: no description of method used to guarantee no communication between care givers or participants and assessors
Incomplete outcome data (attrition bias) All outcomes	Low risk	88 randomised, 85 analysed Quote (p 660‐1): "If a patient missed a visit, we used the score from the previous visit". Comment: few lost to follow‐up, well‐balanced number and reasons between groups
Selective reporting (reporting bias)	Unclear risk	Comment: no protocol was available. The pre‐specified outcomes mentioned in the methods section appeared to have been reported