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. 2021 Apr 19;2021(4):CD011535. doi: 10.1002/14651858.CD011535.pub4

UNCOVER‐2 2015.

Study characteristics
Methods RCT, active, placebo‐controlled, double‐blind
Date of study: 10 May 2012 ‐ 7 May 2015
Location: 118 centres in Europe, Australia, North America
Participants Randomised: 1224 participants (mean age 45 years, 821 male)
Inclusion criteria

  • Participants with moderate‐severe psoriasis (PASI ≥ 12 or BSA ≥ 10), age ≥ 18 years


Exclusion criteria

  • Pregnancy, immunosuppression, kidney insufficiency, liver insufficiency, past history of malignant tumours, active infection, uncontrolled cardiovascular disorder, uncontrolled diabetes, uncontrolled hypertension

  • Had received etanercept and anti IL17


Dropouts and withdrawals

  • 63/1224 (5%)

  • Ixekizumab 4‐week group (19), ixekizumab 2‐week group (9), etanercept group (25), placebo (10)

  • AEs: ixekizumab 4‐week group (5), ixekizumab 2‐week group (4), etanercept (5), placebo (1)

  • Protocol violation: ixekizumab 4‐week group (5), ixekizumab 2‐week group (2), etanercept (4), placebo (2)

  • Participant decision: ixekizumab 4‐week group (6), ixekizumab 2‐week group (2), etanercept (8), placebo (1)

  • Lost to follow‐up: ixekizumab 4‐week group (2), ixekizumab 2‐week group (0), etanercept (5), placebo (1)

  • Investigator decision: ixekizumab 4‐week group (0), ixekizumab 2‐week group (1), etanercept (0), placebo (1)

  • Absence of efficacy: ixekizumab 4‐week group (1), ixekizumab 2‐week group (0), etanercept (3), placebo (3)
Interventions Intervention
A. Ixekizumab (n = 347), SC, 80 mg, 2 injections week 0, 1 injection monthly
Control intervention
B. Ixekizumab (n = 351), SC, 80 mg, 2 injections week 0, 1 injection eow
C. Etanercept (n = 358), SC, 50 mg 1 injection twice weekly
D. Placebo (n = 168), SC
Outcomes Assessments at 12 weeks
Primary outcomes of the trial

  • PGA 0‐1

  • PASI 75


Secondary outcomes of the trial

  • PASI 90

  • DLQI

  • AEs
Notes Funding source:
Quote (p 543): “The funder Eli Lilly. Data were collected by investigators, gathered by Parexel International, and analysed by the funder”. agents and collected and analysed the data. All the authors had full access to the data”.
Declarations of interest, Quote (pp 550‐1): "CEMG has received grants and personal fees from Eli Lilly, Abbvie, Janssen, Novartis, Sandoz, Pfizer, and GlaxoSmithKline; personal fees from Actelion, Amgen, and UCB Pharma; grants from LEO Pharma and Merck Sharp & Dohme; and is president of the International Psoriasis Council. KR has received personal fees from AbbVie, Amgen, Biogen, Celgene, Forward Pharma, Janssen‐Cilag, LEO Pharma, Eli Lilly, Medac, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, and Takeda. ML is an employee of the Mount Sinai Medical Center which receives research funds from AbGenomics, AbbVie, Amgen, Anacor, Aqua, Canfite Biopharma, Celgene, Clinuvel, Coronado Biosciences, Ferndale, Lilly, Janssen Biotech, LEO Pharmaceuticals, Merz, Novartis, Pfizer, Sandoz, and Valeant. PvdK has received grants from Celgene, Centocor, Allmiral, Pfizer, Philips, AbbVie, Eli Lilly, Galderma, Novartis, Janssen Cilag, and Leo Pharma; and has served as a speaker for Amgen, a consultant for Sandoz and Mitisibishu, and a speaker and consultant for Celgene, AbbVie, Eli Lilly, Galderma, Novartis, Janssen Cilag, and Leo Pharma. CP has received grants and personal fees from Amgen, Abbvie, Celgene, Eli Lilly, Novartis, Janssen, Pfizer, and Leo Pharma. KP has received honoraria as consultant and/or scientific officer and/or advisory board and/or steering committee member and/or acted as a paid speaker and/ or participated in clinical trials and/or received clinical research grants sponsored by 3M, Abbott/AbbVie, Akesis, Akros, Allergan, Alza, Amgen, Anacor, Apotex, Astellas, Baxter, Berlex, Biogen, Boehringer Ingelheim, Celgene, Celtic, Centocor, Cipher, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Fujisawa, Funxional Therapeutics, Galderma, Genentech, Genexion, GlaxoSmithKline, Isotechnika, Janssen, Janssen Biotech, Johnson & Johnson, Kataka, Kirin, Kyowa, Leo Pharma, Lypanosys, Medical Minds, Medimmune, Merck, Mitsubishi, Novartis, NovImmune, Pan Genetics, Pfizer, Roche, Regneron, Merck‐Serono, Stiefel, Takeda, UCB, Vertex, Wyeth/Pfizer, and Xoma. AM has served as an advisory board member and/or consultant and/or investigator and/or speaker and/or received compensation in the form of grants and/or honoraria from AbbVie, Allergan, Amgen, ApoPharma, Boehringer Ingelheim, Celgene, Convoy Therapeutics, Eli Lilly, Genentech, Janssen Biotech, LEO Pharma, Merck, Novartis, Pfizer, Symbio and Maruho, Syntrix, Wyeth, and XenoPort. GSC, JE, LZ, RJS, SB, DKB, OOO, MPH, and BJN were employees of and hold stock in Eli Lilly & Co during the conduct of this study. "
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Quote (p 542): “randomly assigned”, “An interactive voice response system"
Comment: probably done
Allocation concealment (selection bias) Low risk Quote (p 542): “An interactive voice response system was used to assign double‐blind investigational product to every patient. Site personnel confirmed that they had located the correct assigned investigational product package by entering a confirmation number found in the package into to IVRS”
Comment: clearly defined
Blinding of participants and personnel (performance bias)
All outcomes Low risk Quote (p 542): “Patients, investigators and study personnel were masked to the treatment allocation. A double‐dummy design was used”
Comment: clearly defined
Blinding of outcome assessment (detection bias)
All outcomes Low risk Quote (p 542): “Patients, investigators and study personnel were masked to the treatment allocation. A double‐dummy design was used”
Comment: clearly defined
Incomplete outcome data (attrition bias)
All outcomes Low risk Randomly assigned 1224, analysed 1224
Management of missing data:
Quote (p 543): “All missing data were imputed using non‐responder imputation (NRI)”
Comment: probably done
Selective reporting (reporting bias) Low risk Comment: the protocol for the study was available on ClinicalTrials.gov (NCT01597245)
One prespecified outcome in the protocol missing from the Results section (assessment of efficacy at 60 weeks), but as we assessed outcomes at induction phase (between 8 ‐ 24 weeks), we judged that the risk of selective reporting was low