Vaclavkova 2014

Methods	RCT, active/placebo‐controlled, double blind Date of study: 22 September 2010‐24 October 2012 Location: 58 centres in Europe and Russia
Participants	Randomised: 326 participants (mean age 40 years, 245 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 10, BSA ≥ 10), age 18‐60 years Exclusion criteria Immunosuppressive treatment for other diseases than psoriasiss Had an active infection Had past history of malignant tumours Dropouts and withdrawals 48/326 (14.7%); ponesimod 20 group (17), ponesimod 40 group (20), placebo group (11) Patient decision: ponesimod 20 group (4), ponesimod 40 group (3), placebo group (7) AE and patient decision: ponesimod 20 group (1), ponesimod 40 group (1), placebo group (1) AEs: ponesimod 20 group (6), ponesimod 40 group (12), placebo group (0) Withdrew consent: ponesimod 20 group (3), ponesimod 40 group (3), placebo group (0) Lack of efficacy: ponesimod 20 group (1), ponesimod 40 group (0), placebo group (1) Lack of efficacy and patient decision: ponesimod 20 group (0), ponesimod 40 group (0), placebo group (1) Administrative : ponesimod 20 group (2), ponesimod 40 group (1), placebo group (1)
Interventions	Intervention A. Ponesimod (n = 126), orally, 10 mg for 7 days then 20 mg, 16 weeks B. Ponesimod (n = 133), orally, 10 mg for 7 days then 20 mg days 8 ‐15 then 40 mg, 16 weeks Control intervention C. Placebo (n = 67), orally, 16 weeks
Outcomes	Assessments at 16 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial PGA 0 or 1 PASI 90 Change from baseline pain psoriatic arthritis
Notes	Funding (p 2044): "This study was sponsored by Actelions Pharmaceuticals" Declarations of interest (p 2044): "AV, MB, and DD’A were employees and stockholders of Actelion Pharmaceuticals when the study was done. SC has been lecturer, consultant, or both, for AbbVie, Janssen‐Cilag, Leo‐Pharma, Merck, Novartis, and Pfizer. MS has received personal fees for statistical consultancy from Actelion Pharmaceuticals and SDE Research. PA, PH, and P‐GS declare that they have no competing interests."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 2037): "A unique seven‐digit randomisation number was assigned to each patient by an independent service provider (ICON Clinical Research, Dublin, Ireland) via an interactive voice or internet‐based response system" Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (p 2037): "A unique seven‐digit randomisation number was assigned to each patient by an independent service provider (ICON Clinical Research, Dublin, Ireland) via an interactive voice or internet‐based response system" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 2037): "The investigational drug and matching placebo were identical in appearance and packaging...The primary investigator, care providers, patients, and sponsor were unaware of study treatment assignment and lymphocyte count. An independent physician monitored patients after the first dose was administered or increased until the end of the study." Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 2037): "The investigational drug and matching placebo were identical in appearance and packaging...The primary investigator, care providers, patients, and sponsor were unaware of study treatment assignment and lymphocyte count. An independent physician monitored patients after the first dose was administered or increased until the end of the study." Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 326, analysed 326 Quote (p 2037): "All randomised patients were assessed by intention‐to‐treat for the primary, secondary, and all efficacy endpoints in the induction period... Missing or invalid values were handled with nonresponder imputation" Comment: ITT analyses
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01208090). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported