PRIME 2017.

Study characteristics
Methods	RCT, active‐controlled, open‐label study Date of study: June 2015 ‐ June 2016 Location: USA (multicentric) Phase 3
Participants	Randomised: 202 participants Inclusion criteria Men or women, must be ≥ 18 years of age at the time of screening Chronic plaque‐type psoriasis diagnosed for ≥ 6 months before randomisation Patients with moderate‐severe plaque psoriasis who are candidates for systemic therapy as defined at randomisation by: PASI score of > 10 BSA) > 10% DLQI > 10 Inadequate response, intolerance or contraindication to topical psoriasis treatment as documented in the patient's medical history or reported by the patient or determined by the investigator at screening Exclusion criteria Previous systemic treatment of plaque psoriasis or known contraindication for systemic therapy at baseline Ongoing use of other prohibited psoriasis and non‐psoriasis treatment Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations Severe liver diseases Severe gastrointestinal diseases including but not limited to ventricular and duodenal ulcers Severe kidney diseases or serum creatinine above 1 x ULN Known haematological disease or lab abnormalities Pregnancy, breast feeding, or unwillingness/inability to use appropriate measures of contraception (if necessary) Dropouts and withdrawals 60/202 (2%): Secu group (6), FAEs group (56) Did not receive allocated intervention: Secu group (0), FAEs group (2) AEs: Secu group (2), FAEs group (32) Patient: Secu group (2), FAEs group (13) Lost to follow‐up: Secu group (2), FAEs group (2) Other: Secu group (0), FAEs group (3)
Interventions	Intervention A. Secukinumab (300 mg at weeks 0, 1, 2, 3, 4, 8, 12, 16 and 20), n = 105 Control intervention B. Fumaderm® (week 0: 1 tablet of Fumaderm® INITIAL in the evening, n =97 Week 1: 1 tablet Fumaderm® INITIAL, in the morning and evening Week 2: 1 tablet Fumaderm® INITIAL in the morning, at noon and in the evening until the last tablet of a 40‐tablet‐blister is consumed Week 2‐3: At the day after the last tablet of the Fumaderm® INITIAL 40‐tablet‐blister is consumed and through week 3, 1 tablet of Fumaderm® in the evening Week 4: 1 tablet Fumaderm® in the morning and evening Week 5: 1 tablet Fumaderm® in the morning, at noon and in the evening Week 6: 1 tablet of Fumaderm® in the morning and at noon, 2 tablets of Fumaderm® in the evening Week 7: 2 tablets of Fumaderm® in the morning, 1 tablet of Fumaderm® at noon, 2 tablets of Fumaderm® in the evening Weeks 8‐24: 2 tablets of Fumaderm® in the morning, at noon and in the evening)
Outcomes	At week 24 Primary outcome PASI 75 Secondary outcomes PASI 90 IGA 0/1 DLQI
Notes	Funding Quote (p 1024): "Novartis Pharma GmbH" Conflicts of interest Quote (Appendix): " M.S. is an advisor and/or paid speaker for and/or has participated in clinical trials sponsored by AbbVie, Actelion, Almirall, Biogen, Boehringer Ingelheim, Celgene, GlaxoSmithKline, Janssen Cilag, LEO Pharma, Eli Lilly, Merck Sharp & Dohme, Mibe, Mundipharma, Novartis, Pfizer, Regeneron and Sanofi. U.M. has been an advisor for and/or received speaker honoraria and/or grants from and/or participated in clinical trials sponsored by Abbott/AbbVie, Almirall Hermal, Amgen, Biogen Idec, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, Foamix, Forward Pharma, Janssen Cilag, LEO Pharma, Medac, MSD, Miltenyi Biotech, Novartis, Pfizer, VBL and Xenoport. M.A. has served as a consultant for, or has been a paid speaker for clinical trials sponsored by AbbVie, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Eli Lilly, GlaxoSmithKline, Janssen Cilag, LEO Pharma, Medac, Merck, MSD, Novartis, Pfizer, UCB and Xenoport. D.T. is an advisor or consultant for AbbVie, Amgen, Biogen Idec, Cel‐gene, Dignity, Eli Lilly, Galapagos, GlaxoSmithKline, Janssen, LEO Pharma, Maruho, Mitsubishi, Mundipharma, Novartis, Pfizer, Sandoz and Xenoport. He has participated in clinical trials sponsored by AbbVie, Almirall, Amgen, Astellas, Biogen Idec, Boehringer Ingelheim, Celgene, Dignity, Eli Lilly, Forward Pharma, GlaxoSmithKline, LEO Pharma, Janssen Cilag, Maruho, MSD, Mitsubishi Pharma, Novartis, Pfizer, Roche and Sandoz. He has received honoraria from AbbVie, Biogen Idec, Celgene, Janssen Cilag, LEO Pharma, Pfizer, Roche Possay, Novartis and Mundipharma. K.R. has served as an advisor and/or paid speaker for, and/or has participated in clinical trials sponsored by AbbVie, Amgen, Biogen, Boehringer Ingelheim Pharma, Celgene, Centocor, Covagen, Forward Pharma, GlaxoSmithKline, Janssen Cilag, LEO Pharma, Eli Lilly, Medac, Merck Sharp & Dohme, Novartis, Ocean Pharma, Pfizer, Regeneron, Takeda, UCB Pharma and Xenoport. N.M., C.S., C.H. and J.K. are employees of and/or own stock in Novartis"
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote (p 1025): "This 24‐week, randomized, open‐label, active‐comparator, parallel‐group, superiority study was conducted... Eligible patients were randomized 1: 1 to receive subcutaneous injections of secukinumab 300 mg or oral FAEs per label, via an automated randomization list. Randomization numbers were assigned to patients by the investigators in consecutive order, who then assigned the treatment displayed on the card. Randomization lists and sealed envelopes were generated by personnel who were not otherwise involved in the trial." Comment: Probably done
Allocation concealment (selection bias)	Low risk	Quote (p 1025): "This 24‐week, randomized, open‐label, active‐comparator, parallel‐group, superiority study was conducted... Eligible patients were randomized 1: 1 to receive subcutaneous injections of secukinumab 300 mg or oral FAEs per label, via an automated randomization list. Randomization numbers were assigned to patients by the investigators in consecutive order, who then assigned the treatment displayed on the card. Randomization lists and sealed envelopes were generated by personnel who were not otherwise involved in the trial." Comment: Probably done
Blinding of participants and personnel (performance bias) All outcomes	High risk	Quote (p 1025): "This 24‐week, randomized, open‐label, active‐comparator, parallel‐group, superiority study was conducted... The blinded assessor and all involved personnel were instructed to desist from any discussions regarding safety, efficacy and treatment allocation of the study and patients in the presence of the blinded assessor. Efficacy parameters were assessed by blinded assessors who were not involved in any other study procedures and who did not have access to the allocation data or case report forms." Comment: Participants not blinded
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote (p 1025): "This 24‐week, randomized, open‐label, active‐comparator, parallel‐group, superiority study was conducted... The blinded assessor and all involved personnel were instructed to desist from any discussions regarding safety, efficacy and treatment allocation of the study and patients in the presence of the blinded assessor. Efficacy parameters were assessed by blinded assessors who were not involved in any other study procedures and who did not have access to the allocation data or case report forms." Comment: Probably done
Incomplete outcome data (attrition bias) All outcomes	High risk	Dealing with missing data Quote (p 1026): "Efficacy end points were assessed for the full analysis set, consisting of all randomized patients who had received at least one dose of study drug. Between treatments, comparisons were made by logistic regression models adjusted for centre and baseline values of PASI scores. Odds ratios (ORs), 95% confidence intervals (CIs) and P‐values were derived from these models. Patients with missing assessments were considered responders if they had already met the response criterion at the time of dropout for the primary end point and all other end points where response was investigated. Otherwise they were considered nonresponders" Randomized 202, analyzed 201 Unbalance proportion regarding discontinuation: 5.7% for Secukinumab vs 57.7% for FAE
Selective reporting (reporting bias)	Low risk	Comment: the protocol for the study was available on ClinicalTrials.gov (NCT02474082) The prespecified outcomes and those mentioned in the Methods section appeared to have been reported Results are posted on ClinicalTrials.gov