NCT03331835.

Study characteristics
Methods	RCT, active‐controlled, open‐label study with blinded assessment of the efficacy outcome Date of study: November 2017 ‐ March 2019 Location: Germany (30 sites) Phase 4
Participants	Randomised: 210 participants Inclusion criteria Men or women ≥ 18 years of age at the time of screening Chronic plaque‐type psoriasis diagnosed at least 6 months before randomisation Moderate‐to‐severe plaque psoriasis in whom topical therapy is not adequate and who are candidates for systemic therapy, defined at randomisation by PASI > 10, affected BSA > 10%, and DLQI > 10 No known history of active tuberculosis Negative test for tuberculosis taken at screening (negative Quantiferon test) Participant and their designee is/are capable of administering subcutaneous injections Exclusion criteria Previous or current systemic treatment of plaque psoriasis or known contraindication for systemic therapy Previous or current PUVA (psoralens and ultraviolet A) therapy Washouts and non‐permitted drugs: Have received phototherapy (UVA light therapy without psoralens, UVB light therapy, excimer laser, tanning beds etc. within 4 weeks of baseline, or have had topical psoriasis treatment within 2 weeks of baseline (exceptions: bland emollients without urea or beta or alpha hydroxy acids); have received any biologic immune modulating treatments used for indication other than psoriasis within 4 weeks of baseline or within a period of 5 half‐lives of the IMP, whichever is longer; have received any other systemic immune modulating treatment (including but not limited to oral retinoids, methotrexate, calcineurin inhibitors, oral or parenteral corticosteroids etc. used for indications other than psoriasis) within 4 weeks of baseline or within a period of 5 half‐lives of the IMP, whichever is longer Any of the following laboratory abnormalities at screening: Leukocyte cell count below 3 × 109/L or lymphocyte count below 0.7 × 109/L; Aspartate aminotransferase (AST) or alanine transferase (ALT) > 2 × ULN (upper level of normal limit); Absolute neutrophil count < 2 × 109/L; Serum creatinine > ULN History of depressive disorder within the last 2 years including current antidepressive treatment A history of suicidal behaviour (suicide attempt) Any suicidal ideation of severity 4 or 5 based on the eC‐SSRS questionnaire at screening A PHQ‐8 score of ≥ 10 corresponding to moderate‐to‐severe depression at screening Baseline characteristics N = 210 and 69% men Dropouts and withdrawals 61/210 (29%): 14/105 Brodalimumab and 47/105 Fumaric acid esthers Reasons not stated
Interventions	Intervention A. Brodalumab (Kyntheum® (brodalumab) pre‐filled syringe 210 mg/1.5 mL solution for subcutaneous injections. First 3 injections are administered weekly, and thereafter every 2 weeks (Q2W)), n = 105 Control interventions B. Fumaric acid esters (Fumaderm® initial dose tablets (30 mg dimethyl fumarate, 67 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) Fumaderm® tablets (120 mg dimethyl fumarate, 87 mg ethyl hydrogen fumarate calcium salt, 5 mg ethyl hydrogen fumarate magnesium salt, 3 mg ethyl hydrogen fumarate zinc salt) Fumaderm® tablets are administered orally up to 3 times daily in accordance with the dosing scheme in the label), n = 105
Outcomes	At week 24 Primary composite outcome PASI 75 ‐ IGA 0/1 Secondary outcomes At least 90% improvement from baseline at week 24 in PASI (Time frame: baseline to week 24) 100% improvement from baseline at week 24 in PASI (Time frame: baseline to week 24) Change from baseline at week 24 in PASI score (Time frame: baseline to week 24) PASI improvement (%) from baseline at week 24 (Time frame: baseline to week 24) Change from baseline at week 24 in affected BSA (Time frame: baseline to week 24) Change From Baseline at Week 24 in DLQI (Time Frame: Baseline to week 24) DLQI Total Score of 0 or 1 at Week 24 (Time Frame: week 24)
Notes	Funding: Quote (ClinicalTrials.gov) LEO pharma Conflict of interest: not stated RoB completed according to ClinicalTrials.gov protocol
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: (protocol p46) Randomisation will be with stratification by body weight (<100 kg or ≥100 kg) using an IWRS system. Coments: adequate process
Allocation concealment (selection bias)	Low risk	Quote (study protocol p46):"Treatment assignment will be pre‐planned according to a computer generated randomisation schedule in a 1:1 ratio. Randomisation will be with stratification by body weight (<100 kg or ≥100 kg) using an IWRS system". Comment: probably done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote (study protocol p46):"This is an open‐label trial... Blinded assessments of PASI, sPGA, BSA, and NAPSI will be performed. Blinded assessors who perform the assessment must be medically qualified physicians trained in the assessments. During the assessments, the subjects will be instructed not to reveal the treatment allocation and the blinded assessor must avoid asking questions that could reveal treatment allocation. All involved personnel will be instructed to desist from any discussions regarding safety, efficacy, treatment allocation of the study and subjects in the presence of the blinded assessor. In case a blinded assessor becomes unblinded, a new assessor should be appointed to perform the assessments of the subject going forward."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (study protocol p46):"This is an open‐label trial... Blinded assessments of PASI, sPGA, BSA, and NAPSI will be performed. Blinded assessors who perform the assessment must be medically qualified physicians trained in the assessments. During the assessments, the subjects will be instructed not to reveal the treatment allocation and the blinded assessor must avoid asking questions that could reveal treatment allocation. All involved personnel will be instructed to desist from any discussions regarding safety, efficacy, treatment allocation of the study and subjects in the presence of the blinded assessor. In case a blinded assessor becomes unblinded, a new assessor should be appointed to perform the assessments of the subject going forward."
Incomplete outcome data (attrition bias) All outcomes	High risk	Dealing with missing data: Quote (ClinicalTrials.gov and study protocol p7):"All subjects randomised are included in the full analysis set (FAS) and will be used for efficacy analyses. Missing data for categorical endpoints will be imputed with non‐responder imputation. Missing data for continuous endpoints will be dealt with by a mixed model for repeated measurements." Randomly assigned 210 Safety set analysis 206; Full set analysis 196/185/81 Comment: not ITT analysis, reasons for withdrawal not reported
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT03331835) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported Results are posted on ClinicalTrials.gov