Ohtsuki 2017.

Study characteristics
Methods	RCT, placebo‐controlled, double‐blind trial, phase 2 Date of study: July 2013 ‐ December 2015 Location: Japan
Participants	Randomised: 254 participants Inclusion criteria Japanese men and women ≥ 20 years of age Diagnosis of chronic, stable plaque psoriasis for ≥ 6 months prior to screening as defined by: PASI score ≥ 12 and BSA ≥ 10% Psoriasis considered inappropriate for topical therapy (based on severity of disease and extent of affected area) or has not been adequately controlled or treated by topical therapy in spite of ≥ 4 weeks of prior therapy with ≥ 1 topical medication for psoriasis or per label In otherwise good health based on medical history, physical examination, 12‐lead ECG, serum chemistry, haematology, immunology, and urinalysis Exclusion criteria Other than psoriasis, history of any clinically significant and uncontrolled systemic diseases; any condition, including the presence of laboratory abnormalities, which would place the person at unacceptable risk or confound the ability to interpret the data in the study Prior medical history of suicide attempt or major psychiatric illness requiring hospitalisation within the last 3 years Pregnant or breastfeeding History of or ongoing chronic or recurrent infectious disease Active TB or a history of incompletely‐treated TB Clinically significant abnormality on 12‐lead ECG or on chest radiograph at screening History of HIV infection or have congenital or acquired immunodeficiencies (e.g. Common Variable Immunodeficiency) Hepatitis B surface antigen or hepatitis B core antibody positive at screening; positive for antibodies to hepatitis C at screening Malignancy or history of malignancy, except for treated (i.e. cured) basal cell or squamous cell in situ skin carcinomas or treated (i.e. cured) cervical intraepithelial neoplasia (CIN) or carcinoma in situ of the cervix with no evidence of recurrence within previous 5 years Psoriasis flare within 4 weeks of screening Topical therapy within 2 weeks prior to randomisation or systemic therapy for psoriasis or psoriatic arthritis within 4 weeks prior to randomisation Use of etretinate within 2 years prior to randomisation for women of childbearing potential or within 6 months for men, and within 4 weeks prior to randomisation for women not of childbearing potential Use of phototherapy (i.e. UVB, PUVA) within 4 weeks prior to randomisation or prolonged sun exposure or use of tanning booths or other ultraviolet light sources Use of adalimumab, etanercept, certolizumab pegol, abatacept, tocilizumab, golimumab or infliximab within 12 weeks prior to randomisation; use of ustekinumab, alefacept or briakinumab within 24 weeks prior to randomisation Any investigational drug within 4 weeks prior to randomisation Dropouts and withdrawals 37/254 (14.6%) Apremilast 30 group (9), Apremilast 20 group (16), Placebo group (12) Participant decision: Apremilast 30 group (1), Apremilast 20 group (8), Placebo group (4) Lack of efficacy: Apremilast 30 group (2), Apremilast 20 group (2), Placebo group (1) AEs: Apremilast 30 group (6), Apremilast 20 group (10), Placebo group (3)
Interventions	Intervention: A. Apremilast (30 mg tablet twice a day for 68 weeks), n = 85 Control intervention: B. Apremilast (20 mg tablet twice a day for 68 weeks), n = 85 C. Placebo, n = 84
Outcomes	At week 16 Primary outcome: PASI 75 Secondary outcomes: PGA 0/1 PASI 90 VAS DLQI total score Mental Component Summary (MCS) score of SF‐36 AEs
Notes	Funding Quote (p 883): "The authors received editorial support in the preparation of the manuscript from Kathy Covino, Ph.D., of Peloton Advantage, LLC, funded by Celgene Corporation. This study was funded by Celgene Corporation." Conflict of interest Quote (p 883): "Mamitaro Ohtsuki reports consultancy and speaker fees. Yukari Okubo reports consultancy fees. Shinichi Imafuku reports research funds, consultancy fees and speaker fees. Robert M. Day, Peng Chen, Rosemary Petric and Allan Maroli report stock or shares in Celgene Corporation and/or employment by Celgene Corporation. Osamu Nemoto has no relevant financial or personal relationships and no potential conflicts of interest to declare."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 874): "After the screening period, eligible patients began a 16‐week placebo‐controlled period and were randomized via a centralized interactive web response system or interactive voice response system (1:1:1) to placebo, apremilast 20 mg b.i.d. or apremilast 30 mg b.i.d." Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (p 874): "After the screening period, eligible patients began a 16‐week placebo‐controlled period and were randomized via a centralized interactive web response system or interactive voice response system (1:1:1) to placebo, apremilast 20 mg b.i.d. or apremilast 30 mg b.i.d." Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 874): "This phase 2b multicenter, randomized, double‐blind, placebo‐controlled study" Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 874): "This phase 2b multicenter, randomized, double‐blind, placebo‐controlled study" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	Low risk	Dealing with missing data: Quote (p 874): "Efficacy and safety assessments were conducted for the modified intent‐to‐treat (mITT) population, which included all patients who were randomized and received at least one dose of study medication; patients not dispensed study medication were excluded from the mITT population... For the primary analysis of PASI‐75, missing values were accounted for using the last observation carried forward methodology; multiple sensitivity analyses (including nonresponder imputation [NRI]) were conducted for the primary end‐point" Randomised 254; analysed 254
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01988103) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported.