POLARIS 2020.

Study characteristics
Methods	RCT, active‐controlled, open‐label study Date of study: November 2016 ‐ September 2017 Location: Germany (multicentric) Phase 3
Participants	Randomised: 119 participants Inclusion criteria Diagnosis of plaque‐type psoriasis for ≥ 6 months before the first administration of study drug PASI) ≥ 10 or BSA > 10 at screening and at baseline DLQI > 10 at screening and at baseline Agree not to receive a live virus or live bacterial vaccination during the study, or within 3 months after the last administration of study drug; for information on Bacille Calmette‐Guérin (BCG) vaccination, agree not to receive a BCG vaccination during the study, or within 12 months after the last administration of study drug No dipstick detection of proteins or glucose in urine. If there are signs of proteins and/or glucose on urine test strip, the urine sample must be analysed centrally. Here, protein and glucose levels must not exceed trace levels, example, ≥ (+); 1 re‐test (central urine analysis) is allowed Exclusion criteria History or current signs or symptoms of severe, progressive, or uncontrolled liver or renal insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, haematologic, rheumatologic, psychiatric, or metabolic disturbances Participants with non‐plaque forms of psoriasis (for example, erythrodermic, guttate, or pustular) or with current drug‐induced psoriasis (for example, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) Known allergies, hypersensitivity, or intolerance to guselkumab or its excipients Pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 12 weeks after the last dose of study drug Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well‐being) or that could prevent, limit, or confound the protocol‐specified assessments Dropouts and withdrawals 27/119 (22.7%): Guselkumab group (4), FAEs group (23) Participant decision: Guselkumab group (2), FAEs group (4) Non‐compliance: Guselkumab group (0), FAEs group (1) Lost to follow‐up: Guselkumab group (2), FAEs group (2) AEs: Guselkumab group (0), FAEs group (16)
Interventions	Intervention A. Guselkumab (100 mg administered as 100 mg/mL solution SC by single‐use prefilled syringe (PFS) at weeks 0, 4, 12 and 20), n = 60 Control intervention B. FAEs (to this aim, FAE doses will be slowly increased beginning with increasing doses of Fumaderm initial (containing 30 mg dimethylfumarate) over the first 3 weeks. Thereafter, participants will be switched to Fumaderm tablets (containing 120 mg dimethylfumarate) starting with 1 tablet a day. Fumaderm dose may be increased to a maximum of 3 x 2 tablets a day), n = 59
Outcomes	At week 24 Primary outcome PASI 90 Secondary outcomes PASI 75 DLQI
Notes	Funding Quote (ClinicalTrials.gov): Janssen‐Cilag G.m.b.H Conflict of interest: not stated
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (ClinicalTrials.gov and statistical analysis plan): "Procedures for Randomization Central randomization is implemented in this study. Subjects will be randomly assigned to 1 of 2 treatment groups (1:1 ratio) based on a computer generated randomization schedule prepared before the study by or under the supervision of the sponsor. Therandomization will be balanced by using randomly permuted blocks. The interactive web based eCRF will assign a unique treatment code, which will dictate the treatment assignment at baseline visit of the subject. The investigator will not be provided with randomization codes. The randomization codes will be stored invisible for the investigator in a separate, blind part of the EDC system." Comment: probably done
Allocation concealment (selection bias)	Low risk	Quote (ClinicalTrials.gov and statistical analysis plan): "Procedures for Randomization Central randomization is implemented in this study. Subjects will be randomly assigned to 1 of 2 treatment groups (1:1 ratio) based on a computer generated randomization schedule prepared before the study by or under the supervision of the sponsor. Therandomization will be balanced by using randomly permuted blocks. The interactive web based eCRF will assign a unique treatment code, which will dictate the treatment assignment at baseline visit of the subject. The investigator will not be provided with randomization codes. The randomization codes will be stored invisible for the investigator in a separate, blind part of the EDC system." Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote (ClinicalTrials.gov and statistical analysis plan): "Blinding: As this is an open study, blinding procedures for the treatment are not applicable. However, a blinded efficacy evaluator will assess effectiveness of treatment as described in Section 9.2.3 of the CSP)... An independent, blinded efficacy assessor, approved by the Sponsor, will be designated at each study site to perform all efficacy assessments (BSA%, IGA, ssIGA, and PASI) starting with baseline visit until end of treatment phase (ie, Week 56)" Comment: probably done
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (ClinicalTrials.gov and statistical analysis plan): "Blinding: As this is an open study, blinding procedures for the treatment are not applicable. However, a blinded efficacy evaluator will assess effectiveness of treatment as described in Section 9.2.3 of the CSP)... An independent, blinded efficacy assessor, approved by the Sponsor, will be designated at each study site to perform all efficacy assessments (BSA%, IGA, ssIGA, and PASI) starting with baseline visit until end of treatment phase (ie, Week 56)" Comment: probably done
Incomplete outcome data (attrition bias) All outcomes	High risk	Dealing with missing data: Quote (ClinicalTrials.gov and statistical analysis plan): "Nonresponder imputation will be applied for binary endpoints i.e., subjects with missing data at Week 4/16/24 will be considered non‐responders at Week 4/16/24" Results posted on ClinicalTrials.gov: ITT Unbalance discontinuation proportion (< 1% for Guselkumab and 39% for FAEs)
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT02951533) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported