Zhu LOTUS, 2013

Methods	RCT, placebo‐controlled, double blind (LOTUS) Date of study: 23 October 2009‐07 July 2011 Location: 14 centres in China
Participants	Randomised: 322 participants (mean age 40 years, 248 male) Inclusion criteria Participants with moderate‐severe psoriasis (PASI≥12 and BSA ≥ 10), age >18 years Exclusion criteria Severe uncontrolled or progressive medical conditions Known to be infected with HIV (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or syphilis Dropouts and withdrawals 6/322 (1.86%): ustekinumab group (3), placebo group (3) AEs: ustekinumab group (2), placebo group (1) Other reasons: ustekinumab group (1), placebo group (2)
Interventions	Intervention A. Ustekinumab (n = 160), SC, 45 mg, week 0, week 4, 4weeks Control intervention B. Placebo (n = 162), SC, week 0, week 4, 4weeks
Outcomes	Assessments at 12 weeks Primary outcomes of the trial PASI 75 Secondary outcomes of the trial ‐ PGA 0 /1 ‐ DLQI
Notes	Funding source quote (p 173): "This study was supported by Janssen Research & Development" Declarations of interest (p 173): "Drs Zhu, Zang and Wand served as investigators for this Janssen RD‐sponsored study..."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote (p 167): "The LOTUS study is a phase 3, multicenter, randomized, double blind, placebo‐controlled... Comment: no description of the method used to guarantee random sequence generation
Allocation concealment (selection bias)	Unclear risk	Quote (p 167): Comment: no description of the method used to guarantee allocation concealment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote (p 167): "The LOTUS study is a phase 3, multicenter, randomized, double blind, placebo‐controlled... Comment: placebo‐controlled study
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Quote (p 167): "The LOTUS study is a phase 3, multicenter, randomized, double blind, placebo‐controlled... Comment: no description of the method used to guarantee blinding of outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Randomly assigned 322, analyzed 322 Quote (p 167): "For efficacy analyses, all randomized patients were included... Patients who discontinued study treatment... were considered treatment failures" Comment: ITT analyses
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01008995). The pre‐specified outcomes and those mentioned in the methods section appeared to have been reported

AEs: adverse events; ACR: American College of Rheumatology; ALT: alanine aminotransferase; AST: aspartate aminotransferase; BSA: Body Surface Area; eow: every other week; CIN: cervical intraepithelial neoplasia; DLQI: Dermatology Life Quality Index; ECG: electrocardiogram; HD: high dose; IGA: Investigator’s Global Assessment; IM: intramuscular; ITT: intention‐to‐treat; IV: intravenous; LD: low dose; m‐ITT: modified ITT; MD: medium dose; NAPSI: Nail psoriasis severity index; NBUVB: narrow‐band UVB; PASI: Psoriasis Area and Severity Index; PGA: Physician Global Assessment; PP: per protocol; PSI: Psoriasis Severity Index; PSSI: Psoriasis Scalp Severity Index; PUVA: psoralen plus ultraviolet A; QoL: quality of life; RCT: randomised controlled trial; SC: subcutaneous; SF36: 36‐item Short Form Health Survey; SIAQ: Self‐ Injection Assessment Questionnaire; TB: tuberculosis; TBR: target background ratio; UVB: ultraviolet B; VAS: visual analogue scale