Papp 2013b

Methods	RCT, active/placebo‐controlled, double blind Date of study: April 2006‐May 2007 Location: multicentre (30) in Canada, the Czech Republic, and Germany
Participants	Randomised: 260 participants (mean age 46 years, 163 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 12, BSA > 10%) Age ≥ 18 years Exclusion criteria History of clinically significant medical or psychiatric diseases Pregnancy or lactation History of active Mycobacterium TB infection HIV, hepatitis B or C, history of malignancy within 5 years of screening or evidence of skin conditions Current erythrodermic, guttate or pustular psoriasis Dropouts and withdrawals 47/260 (18%) at 12w; Apremilast (28): AE (8), lack efficiency (8), withdrew consent (4), lost to follow‐up (3), protocol violation (3), other (2) Placebo (19): AE (7), lack efficiency (5), withdrew consent (2), lost to follow‐up (1), protocol violation (2), other(2)
Interventions	Intervention A. Apremilast (n = 173), orally, 10‐20 mg, twice a day, 12 weeks Control intervention B. Placebo (n = 87)
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial PGA PASI 50/90 BSA AEs
Notes	Funding source quote (p 27): "This study was sponsored by Celgene Corporation" Declarations of interest (p27): "Dr Papp is a consultant and investigator for Celgene Corporation, Abbott, Amgen, Centocor, Janssen‐Ortho, Merck, Novartis and Pfizer and an investigator for Astellas, Leo Pharma and Galderma, receiving honoraria and grants. Dr Kaufmann is an investigator for Abbott, Centocor, Leo, Novartis, Wyeth and Celgene Corporation, but has not received financial compensation. The Department of Dermatology received investigator fees for performing the clinical trials. He served as a speaker for Basilea and Allmiral and received honoraria from each. Dr Thac ¸ i is on the advisory board of and is a consultant, investigator and speaker for Abbott, Leo, Novartis, Pfizer, Biogen‐Idec, Janssen‐Cilag and MSD, and received honoraria from each. He is also an investigator for Celgene Corporation. The Department of Dermatology received honoraria ⁄ compensation for conducting studies; no direct compensation was received. Ms Hu receives a salary as an employee of Celgene Corporation. Ms Sutherland receives a salary, stocks and stock options as an employee of Celgene Corporation. Dr Rohane received a salary and stock options as a former employee of Celgene Corporation. "
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote (p 377): " investigators randomised subjects 1 : 1 : 1 to double‐blind treatments for 12 weeks with placebo, apremilast 20 mg QD or apremilast 20 mg twice daily" Comment: no description of the method to guarantee the random sequence generation
Allocation concealment (selection bias)	Low risk	Quote (p 377): "Using an interactive voice response system, investigators randomised subjects 1 : 1 : 1 to double‐blind treatments" Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 377): "One capsule of placebo or apremilast was taken orally in the morning before meals, and one capsule of placebo or apremilast was taken in the evening" Comment: probably done, placebo‐controlled
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 377): "One capsule of placebo or apremilast was taken orally in the morning before meals, and one capsule of placebo or apremilast was taken in the evening" Comment: probably done, placebo controlled
Incomplete outcome data (attrition bias) All outcomes	High risk	260 included / 260 analysed Management of missing data were not stated and substantial number lost to follow‐up (18%)
Selective reporting (reporting bias)	High risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT00606450). The pre‐specified outcomes listed on ClinicalTrials.gov were not detailed, the choice of the primary outcome was not clearly defined. In the methods section, PASI 75 was defined as the primary outcome, no QoL outcomes were listed in the methods section although they were in the protocol on clinicaltrilas.gov