Papp 2012b

Methods	RCT, active/placebo‐controlled, double blind Date of study: September 2008‐October 2009 Location: 35 centres in Canada and USA
Participants	Randomised: 352 participants (mean age 44 years, 221 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI ≥ 12, BSA ≥ 10%) Age ≥ 18 years Exclusion criteria Had a history of, or present, significant disease, including Mycobacterium TB or HIV infection Had a positive screening test for hepatitis B or C Pregnant or breastfeeding Dropouts and withdrawals 65/352 (11%) at 16w; Apremilast 30 twice daily: (18): AE (10), lack efficacy (2), withdrew consent (4), lost to follow‐up (1), Other (1) Apremilast other (31): AE (9), lack efficacy (5), withdrew consent (8), protocol violation (7), other (2) Placebo (16): AE (5), lack efficacy (4), withdrew consent (2), death (1), lost to follow up (2), protocol deviation (1), other (1)
Interventions	Intervention A. Apremilast (n = 88), orally, 30 mg, twice a day, 16 weeks Control intervention B. Apremilast (n = 176), orally, 10‐20 mg twice a day, 16 weeks C. Placebo (n = 88), orally, twice a day 16 weeks
Outcomes	Assessments at 16 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial PGA 0 or 1 PASI 50/90 DLQI SF36
Notes	Funding source quote (p 738): "Funding Celgene Corporation" Declarations of interest quote (p 745): "KP has served as an investigator for Abbott, Amgen, Celgene, Centocor, Galderma, Incyte, Isotechnika, Janssen, Lilly, Medimmune, Merck, Novartis, and Pfizer; an adviser for Abbott, Amgen, Astellas, BMS, Celgene, Centocor, Galderma, Incyte, Isotechnika, Janssen, Johnson & Johnson, Lilly, Medimmune, Merck, Novartis, Pfizer, and UCB; and a speaker for Abbott, Amgen, Astellas, Celgene, Centocor, Isotechnika, Janssen, Novartis, and Pfizer. JCC has served as an investigator for Celgene, Centocor, Novartis, and Pfizer; as a speaker for Centocor and Abbott; and as an adviser for Pfizer, Abbott, and Novartis. LR has been a paid investigator for doing clinical trials for Amgen, Genentech, Abbott, Centocor, Basilea, Leo, Isotechnika, Stiefel, GSK, Galderma, 3‐M, Serono, Novartis, Astellas, UCB, Celgene, Johnson & Johnson, and Pfizer. HS has served as an investigator for Abbott, Centocor, Celgene, Amgen, and Pfizer; as a speaker for Abbott and Centocor; and as an adviser for Centocor. RGL has served as an investigator for Abbott, Centocor, Celgene, Amgen, Pfizer, Johnson & Johnson/Ortho Biotech, and Novartis; as a speaker for Abbott, Centocor, Amgen, Pfizer, Johnson & Johnson/Ortho Biotech, and Novartis; and as an adviser for Abbott, Centocor, Celgene, Amgen, Pfizer, Johnson & Johnson/Ortho Biotech, and Novartis. RTM has served as an investigator for Abbott, Centocor, Celgene, Amgen, Novartis, Lilly, Pfizer, Allergan, and Galderma; as a speaker for Centocor and Amgen; and as an adviser for Centocor. CH and RMD are employees of Celgene Corporation."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 739): "Eligible patients were randomly assigned in a 1:1:1:1 ratio to oral apremilast 10 mg twice daily, apremilast 20 mg twice daily, apremilast 30 mg twice daily, or placebo, with a permuted‐block randomisation list generated by an interactive voice response system (ClinPhone, East Windsor, NJ, USA)." Comment: clearly described
Allocation concealment (selection bias)	Low risk	Quote (p 739): "Eligible patients were randomly assigned in a 1:1:1:1 ratio to oral apremilast 10 mg twice daily, apremilast 20 mg twice daily, apremilast 30 mg twice daily, or placebo, with a permuted‐block randomisation list generated by an interactive voice response system (ClinPhone, East Windsor, NJ, USA)." Comment: clearly described
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 739): "Treatment was double‐blind for the first 16 weeks of the 24‐week treatment phase." Comment: probably done, placebo‐controlled
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 739): "Treatment was double‐blind for the first 16 weeks of the 24‐week treatment phase." Comment: probably done, placebo‐controlled
Incomplete outcome data (attrition bias) All outcomes	Low risk	352 included / 352 analysed Quote (p 740): "Efficacy data were assessed by intention to treat. Missing data were handled with the last‐observation carried‐forward method." Comment: number of lost to follow‐up and reasons comparable across group
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT00773734). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported.