Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.

CEM Griffiths; Mark Lebwohl; Peter van de Kerkhof; Alan Menter; Gregory S Cameron; Janelle Erickson; Lu Zhang; Roberta J Secrest; Susan Ball; Daniel K Braun; Olawale O Osuntokun; Michael P Heffernan; Brian J Nickoloff; David J Kerr; Charles Birbara; William T Ko; William D Koltun; Jonathan S Dosik; Derek Lewis; Alison Ehrlich; Bruce E Strober; Rosalyn E George; Paul Gillum; Tiffani K Hamilton; John A Hoekstra; William Abramovits; Mark G Lebwohl; Patricia C Lee; Maurizio Podda; Tilmann Rieken; Christine Grigat; Johannes Norgauer; Carl Gustav Carus; Gottfried Wozel; Andreas Koerber; Thomas Rosenbach; Grazyna Chodorowska; Romuald Maleszka; Andrzej Kaszuba; Lidia Rudnicka; Elzbieta B Szymanska; Elzbieta Klujszo; Roman Nowicki; Grazyna Wasik; Ira H Thorla; Angela Moore; Kimberly Grande; Jeffrey M Sobell; Benjamin Lockshin; John M Humeniuk; Bruce G Rankin; Joseph G Delamo; David M Pariser; Craig L Leonardi; Steven A Davis; Laura K Ferris; Marta I Rendon; Jamie D Weisman; Jeffrey S Fromowitz; S Sasha Jazayeri; Robert Nossa; Caius Solovan; Dorin Mihalache; George-Sorin Tiplica; Anca Zbranca-Toporas; Ion Florea; Horia Beti; Nicholas Wainwright; Christopher Griffiths; Sandy McBride; David Burden; John Foerster; Aamir Butt; Andrew Messenger; Adrian Lim; John Su; Stephen Hall; Alan Cooper; Lawrence C Parish; Daniel A Carrasco; Mark A McCune; William P Werschler; Kevin T Belasco; Abe Marcadis; Timothy L Gardner; Scott T Guenthner; Christopher G Nelson; Ben Barankin; Lorne Albrecht; Melinda Gooderham; Yves Poulin; Leslie Rosoph; Jean Sebastien Gauthier; Ronald Vender; Norman Wasel; Shireen Sidhu; Diana Rubel; Peter Foley; Lynda Spelman; Isaac Bodokh; Anne-Benedicte Duval-Modeste; Gerard Guillet; Carle Paul; Jean-Philippe Lacour; Francois Aubin; Guillaume Chaby; Jean-Jacques Grob; Peter Van de Kerkhof; Amphia Ziekenhuis; Wim de Kort; Martiin Bastiaan Van Doorn; Elisabeth Riedl; Robert Strohal; Matthias Schmuth; Wolfgang Salmhofer; Benjamin Lasko; Azhar Toma; Derek Woolner; Kirk Barber; Lyn Guenther; Charles Lynde; Sam Hanna; Aditya Gupta; Rodion Kunynetz; Matthias Hoffmann; Thomas Werfel; Kristian Reich; Beate Brau; Kamran Ghoreschi; Rotraut Moessn; Petr Arenberger; Vladimir Vasku; Alena Machovcova; Carlos Ferrandiz; Lopez Bran Eduardo; Lluis Puig Sanz; Enrique Herrera Ceballos; Jose Lopez Estebaranz; Isabel Belinchon Romero; Ramon Pujol; Francisco Vanaclocha Sebastian; Gregorio Carretero Hernandez; Lara Ferrandiz Pulido; Andrew Blauvelt; Michael Bukhalo; David Stoll; Jeffrey Crowley; Yolanda Helfrich; Stephen Miller; Elyse Rafal; James Solomon; Stephen Schleicher; Joel Schlessinger; Howard Sofen; Zoe Diana Draelos; Johnnie Woodson; Janna Stoessel; Hans Konig; Harald Bruning; Richard Piechatzek; Irina Lohrbacher-Kozak; Christel Contzen; Andrei Khariouzov; Peter Heymer; Kristen Kreutzmann; Hans-Michael Ockenfels; Thomas Wildfeuer; Rudolf Virchow; Uwe Reinhold; Hjalmar Kurzen; Christian Termeer; Alex Rothhaar; Peter Radny; James Coggi; Jeffrey Lenz; Kevin Kuettel; Salem Galal; Eduardo Tschen; Ruth Gilboa; Scott Fretzin; Alan Fleischer; Douglass Forsha; Theresa Knoepp; Walter Nahm; Stephanie Mehlis; Martin Menter; Paul Yamauchi; Ronald Savin; Sylke Gellrich; Bernd Kardorff; Anita Rütter; Dagmar Ludolph-Hauser; Michael Sebastian; Athanasios Tsianakas; Doerte Wolf; Wiebke Ludwig-Peitsch; Sandra Philipp; Mathias Augustin; Rumyana Yankova; Jana Kazandjieva; Iliya Tsingov; Tzetza Vlaeva; Neil Sadick; Joseph Fowler; Artis Truett; Jashin Wu; Michael Bernhardt; Mark Lee; Jerry Bagel; Frederick Behringer; Leon Kircik; Javier Alonso-Llamazares; Susan Hole; Phoebe Rich; Kenneth Gordon; James Campbell; Miroslava Kadurina; Maria Poznanska; Lidia Rajzer; Kamila Padlewska; Remigio F Gonzalez Soto; Javier A Gonzalez; Lajos Kemeny; Eva Remenyik; Zsuzsanna Karolyi; Noemi Bakos; Edina Nemes; Levente Kovago; Eniko Telegdy; Kristina Callis-Duffin; Alice Gottlieb; Jennifer Soung; April Armstrong; David Norris; Richard Thomas; Stewart Adams; Kim Papp; Richard Langley; Isabelle Delorme; Michael Robern; Youwen Zhou; Jerry Tan; Mani Raman; Shakti Sharma; Catherine Maari; Rolland Gyulai; Dalma Varszegi; Ivan Orojan; Dosa Piroska; Ildiko Vincze; Eva Melegh; Krylatskie Cholmy; Yuriy N Perlamutrov; Krasnodarskiy Kray; Nikolay Murashkin; Alexey Sukharev; Anton Edin; Yana Smirnova; Kirill Rudinskiy; Georg Popp; Wolfgang Vanscheidt; Fachbereich Medizin; Johann Wolfgang; Roland Kaufmann; Diamant Thaci; Sandrine Benoit; Andrea Thron; Petra Kast; Klinische Studien; Martin Kaatz; Rudolf Schopf; Elisabeth Theis; Christine Paschen; Liebhild Stratmann; Andrea Graefe; Kristin Kreutzmann; Elizaveta Degtyareva; Konstantin Raznatovskiy; Olga Stetsiouk; Stanislav Givirovskiy; Petr Chizhov; Fernando Valenzuela; [Unknown] Fernandez; Pablo Gonzalez; Ricardo Luis Galimberti; Gabriel Alejandro Magarinos

doi:10.1016/S0140-6736(15)60125-8

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.

CEM Griffiths, Mark Lebwohl, Peter van de Kerkhof, Alan Menter, Gregory S Cameron, Janelle Erickson, Lu Zhang, Roberta J Secrest, Susan Ball, Daniel K Braun, Olawale O Osuntokun, Michael P Heffernan, Brian J Nickoloff, David J Kerr (Collaborator), Charles Birbara (Collaborator), William T Ko (Collaborator), William D Koltun (Collaborator), Jonathan S Dosik (Collaborator), Derek Lewis (Collaborator), Alison Ehrlich (Collaborator)Bruce E Strober (Collaborator), Rosalyn E George (Collaborator), Paul Gillum (Collaborator), Tiffani K Hamilton (Collaborator), John A Hoekstra (Collaborator), William Abramovits (Collaborator), Mark G Lebwohl (Collaborator), Patricia C Lee (Collaborator), Maurizio Podda (Collaborator), Tilmann Rieken (Collaborator), Christine Grigat (Collaborator), Johannes Norgauer (Collaborator), Carl Gustav Carus (Collaborator), Gottfried Wozel (Collaborator), Andreas Koerber (Collaborator), Thomas Rosenbach (Collaborator), Grazyna Chodorowska (Collaborator), Romuald Maleszka (Collaborator), Andrzej Kaszuba (Collaborator), Lidia Rudnicka (Collaborator), Elzbieta B Szymanska (Collaborator), Elzbieta Klujszo (Collaborator), Roman Nowicki (Collaborator), Grazyna Wasik (Collaborator), Ira H Thorla (Collaborator), Angela Moore (Collaborator), Kimberly Grande (Collaborator), Jeffrey M Sobell (Collaborator), Benjamin Lockshin (Collaborator), John M Humeniuk (Collaborator), Bruce G Rankin (Collaborator), Joseph G Delamo (Collaborator), David M Pariser (Collaborator), Craig L Leonardi (Collaborator), Steven A Davis (Collaborator), Laura K Ferris (Collaborator), Marta I Rendon (Collaborator), Jamie D Weisman (Collaborator), Jeffrey S Fromowitz (Collaborator), S Sasha Jazayeri (Collaborator), Robert Nossa (Collaborator), Caius Solovan (Collaborator), Dorin Mihalache (Collaborator), George-Sorin Tiplica (Collaborator), Anca Zbranca-Toporas (Collaborator), Ion Florea (Collaborator), Horia Beti (Collaborator), Nicholas Wainwright (Collaborator), Christopher Griffiths (Collaborator), Sandy McBride (Collaborator), David Burden (Collaborator), John Foerster (Collaborator), Aamir Butt (Collaborator), Andrew Messenger (Collaborator), Adrian Lim (Collaborator), John Su (Collaborator), Stephen Hall (Collaborator), Alan Cooper (Collaborator), Lawrence C Parish (Collaborator), Daniel A Carrasco (Collaborator), Mark A McCune (Collaborator), William P Werschler (Collaborator), Kevin T Belasco (Collaborator), Abe Marcadis (Collaborator), Timothy L Gardner (Collaborator), Scott T Guenthner (Collaborator), Christopher G Nelson (Collaborator), Ben Barankin (Collaborator), Lorne Albrecht (Collaborator), Melinda Gooderham (Collaborator), Yves Poulin (Collaborator), Leslie Rosoph (Collaborator), Jean Sebastien Gauthier (Collaborator), Ronald Vender (Collaborator), Norman Wasel (Collaborator), Shireen Sidhu (Collaborator), Diana Rubel (Collaborator), Peter Foley (Collaborator), Lynda Spelman (Collaborator), Isaac Bodokh (Collaborator), Anne-Benedicte Duval-Modeste (Collaborator), Gerard Guillet (Collaborator), Carle Paul (Collaborator), Jean-Philippe Lacour (Collaborator), Francois Aubin (Collaborator), Guillaume Chaby (Collaborator), Jean-Jacques Grob (Collaborator), Peter Van de Kerkhof (Collaborator), Amphia Ziekenhuis (Collaborator), Wim de Kort (Collaborator), Martiin Bastiaan Van Doorn (Collaborator), Elisabeth Riedl (Collaborator), Robert Strohal (Collaborator), Matthias Schmuth (Collaborator), Wolfgang Salmhofer (Collaborator), Benjamin Lasko (Collaborator), Azhar Toma (Collaborator), Derek Woolner (Collaborator), Kirk Barber (Collaborator), Lyn Guenther (Collaborator), Charles Lynde (Collaborator), Sam Hanna (Collaborator), Aditya Gupta (Collaborator), Rodion Kunynetz (Collaborator), Matthias Hoffmann (Collaborator), Thomas Werfel (Collaborator), Kristian Reich (Collaborator), Beate Brau (Collaborator), Kamran Ghoreschi (Collaborator), Rotraut Moessn (Collaborator), Petr Arenberger (Collaborator), Vladimir Vasku (Collaborator), Alena Machovcova (Collaborator), Carlos Ferrandiz (Collaborator), Lopez Bran Eduardo (Collaborator), Lluis Puig Sanz (Collaborator), Enrique Herrera Ceballos (Collaborator), Jose Lopez Estebaranz (Collaborator), Isabel Belinchon Romero (Collaborator), Ramon Pujol (Collaborator), Francisco Vanaclocha Sebastian (Collaborator), Gregorio Carretero Hernandez (Collaborator), Lara Ferrandiz Pulido (Collaborator), Andrew Blauvelt (Collaborator), Michael Bukhalo (Collaborator), David Stoll (Collaborator), Jeffrey Crowley (Collaborator), Yolanda Helfrich (Collaborator), Stephen Miller (Collaborator), Elyse Rafal (Collaborator), James Solomon (Collaborator), Stephen Schleicher (Collaborator), Joel Schlessinger (Collaborator), Howard Sofen (Collaborator), Zoe Diana Draelos (Collaborator), Johnnie Woodson (Collaborator), Janna Stoessel (Collaborator), Hans Konig (Collaborator), Harald Bruning (Collaborator), Richard Piechatzek (Collaborator), Irina Lohrbacher-Kozak (Collaborator), Christel Contzen (Collaborator), Andrei Khariouzov (Collaborator), Peter Heymer (Collaborator), Kristen Kreutzmann (Collaborator), Hans-Michael Ockenfels (Collaborator), Thomas Wildfeuer (Collaborator), Rudolf Virchow (Collaborator), Uwe Reinhold (Collaborator), Hjalmar Kurzen (Collaborator), Christian Termeer (Collaborator), Alex Rothhaar (Collaborator), Peter Radny (Collaborator), James Coggi (Collaborator), Jeffrey Lenz (Collaborator), Kevin Kuettel (Collaborator), Salem Galal (Collaborator), Eduardo Tschen (Collaborator), Ruth Gilboa (Collaborator), Scott Fretzin (Collaborator), Alan Fleischer (Collaborator), Douglass Forsha (Collaborator), Theresa Knoepp (Collaborator), Walter Nahm (Collaborator), Stephanie Mehlis (Collaborator), Martin Menter (Collaborator), Paul Yamauchi (Collaborator), Ronald Savin (Collaborator), Sylke Gellrich (Collaborator), Bernd Kardorff (Collaborator), Anita Rütter (Collaborator), Dagmar Ludolph-Hauser (Collaborator), Michael Sebastian (Collaborator), Athanasios Tsianakas (Collaborator), Doerte Wolf (Collaborator), Wiebke Ludwig-Peitsch (Collaborator), Sandra Philipp (Collaborator), Mathias Augustin (Collaborator), Rumyana Yankova (Collaborator), Jana Kazandjieva (Collaborator), Iliya Tsingov (Collaborator), Tzetza Vlaeva (Collaborator), Neil Sadick (Collaborator), Joseph Fowler (Collaborator), Artis Truett (Collaborator), Jashin Wu (Collaborator), Michael Bernhardt (Collaborator), Mark Lee (Collaborator), Jerry Bagel (Collaborator), Frederick Behringer (Collaborator), Leon Kircik (Collaborator), Javier Alonso-Llamazares (Collaborator), Susan Hole (Collaborator), Phoebe Rich (Collaborator), Kenneth Gordon (Collaborator), James Campbell (Collaborator), Miroslava Kadurina (Collaborator), Maria Poznanska (Collaborator), Lidia Rajzer (Collaborator), Kamila Padlewska (Collaborator), Remigio F Gonzalez Soto (Collaborator), Javier A Gonzalez (Collaborator), Lajos Kemeny (Collaborator), Eva Remenyik (Collaborator), Zsuzsanna Karolyi (Collaborator), Noemi Bakos (Collaborator), Edina Nemes (Collaborator), Levente Kovago (Collaborator), Eniko Telegdy (Collaborator), Kristina Callis-Duffin (Collaborator), Alice Gottlieb (Collaborator), Jennifer Soung (Collaborator), April Armstrong (Collaborator), David Norris (Collaborator), Richard Thomas (Collaborator), Stewart Adams (Collaborator), Kim Papp (Collaborator), Richard Langley (Collaborator), Isabelle Delorme (Collaborator), Michael Robern (Collaborator), Youwen Zhou (Collaborator), Jerry Tan (Collaborator), Mani Raman (Collaborator), Shakti Sharma (Collaborator), Catherine Maari (Collaborator), Rolland Gyulai (Collaborator), Dalma Varszegi (Collaborator), Ivan Orojan (Collaborator), Dosa Piroska (Collaborator), Ildiko Vincze (Collaborator), Eva Melegh (Collaborator), Krylatskie Cholmy (Collaborator), Yuriy N Perlamutrov (Collaborator), Krasnodarskiy Kray (Collaborator), Nikolay Murashkin (Collaborator), Alexey Sukharev (Collaborator), Anton Edin (Collaborator), Yana Smirnova (Collaborator), Kirill Rudinskiy (Collaborator), Georg Popp (Collaborator), Wolfgang Vanscheidt (Collaborator), Fachbereich Medizin (Collaborator), Johann Wolfgang (Collaborator), Roland Kaufmann (Collaborator), Diamant Thaci (Collaborator), Sandrine Benoit (Collaborator), Andrea Thron (Collaborator), Petra Kast (Collaborator), Klinische Studien (Collaborator), Martin Kaatz (Collaborator), Rudolf Schopf (Collaborator), Elisabeth Theis (Collaborator), Christine Paschen (Collaborator), Liebhild Stratmann (Collaborator), Andrea Graefe (Collaborator), Kristin Kreutzmann (Collaborator), Elizaveta Degtyareva (Collaborator), Konstantin Raznatovskiy (Collaborator), Olga Stetsiouk (Collaborator), Stanislav Givirovskiy (Collaborator), Petr Chizhov (Collaborator), Fernando Valenzuela (Collaborator), [Unknown] Fernandez (Collaborator), Pablo Gonzalez (Collaborator), Ricardo Luis Galimberti (Collaborator), Gabriel Alejandro Magarinos (Collaborator)

Division of Musculoskeletal & Dermatological Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9-91·8) vs placebo; 48·1% (41·2-55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4-85·7) vs placebo; 33·9% (27·0-40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5-80·8) vs placebo; 35·9% (28·2-43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0-82·8) vs placebo; 30·8% (23·7-37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p

Original language	English
Pages (from-to)	541-551
Journal	Lancet (London, England)
Volume	386
Issue number	9993
DOIs	https://doi.org/10.1016/S0140-6736(15)60125-8
Publication status	Published - 8 Aug 2015

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10.1016/S0140-6736(15)60125-8

Cite this

Griffiths, CEM., Lebwohl, M., van de Kerkhof, P., Menter, A., Cameron, G. S., Erickson, J., Zhang, L., Secrest, R. J., Ball, S., Braun, D. K., Osuntokun, O. O., Heffernan, M. P., Nickoloff, B. J., Kerr, D. J., Birbara, C., Ko, W. T., Koltun, W. D., Dosik, J. S., Lewis, D., ... Magarinos, G. A. (2015). Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials. Lancet (London, England), 386(9993), 541-551. https://doi.org/10.1016/S0140-6736(15)60125-8

@article{5c04afbbf9b14f83b38fdf20bdfda055,

title = "Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.",

abstract = "BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9-91·8) vs placebo; 48·1% (41·2-55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4-85·7) vs placebo; 33·9% (27·0-40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5-80·8) vs placebo; 35·9% (28·2-43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0-82·8) vs placebo; 30·8% (23·7-37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p",

author = "CEM Griffiths and Mark Lebwohl and {van de Kerkhof}, Peter and Alan Menter and Cameron, {Gregory S} and Janelle Erickson and Lu Zhang and Secrest, {Roberta J} and Susan Ball and Braun, {Daniel K} and Osuntokun, {Olawale O} and Heffernan, {Michael P} and Nickoloff, {Brian J} and Kerr, {David J} and Charles Birbara and Ko, {William T} and Koltun, {William D} and Dosik, {Jonathan S} and Derek Lewis and Alison Ehrlich and Strober, {Bruce E} and George, {Rosalyn E} and Paul Gillum and Hamilton, {Tiffani K} and Hoekstra, {John A} and William Abramovits and Lebwohl, {Mark G} and Lee, {Patricia C} and Maurizio Podda and Tilmann Rieken and Christine Grigat and Johannes Norgauer and Carus, {Carl Gustav} and Gottfried Wozel and Andreas Koerber and Thomas Rosenbach and Grazyna Chodorowska and Romuald Maleszka and Andrzej Kaszuba and Lidia Rudnicka and Szymanska, {Elzbieta B} and Elzbieta Klujszo and Roman Nowicki and Grazyna Wasik and Thorla, {Ira H} and Angela Moore and Kimberly Grande and Sobell, {Jeffrey M} and Benjamin Lockshin and Humeniuk, {John M} and Rankin, {Bruce G} and Delamo, {Joseph G} and Pariser, {David M} and Leonardi, {Craig L} and Davis, {Steven A} and Ferris, {Laura K} and Rendon, {Marta I} and Weisman, {Jamie D} and Fromowitz, {Jeffrey S} and Jazayeri, {S Sasha} and Robert Nossa and Caius Solovan and Dorin Mihalache and George-Sorin Tiplica and Anca Zbranca-Toporas and Ion Florea and Horia Beti and Nicholas Wainwright and Christopher Griffiths and Sandy McBride and David Burden and John Foerster and Aamir Butt and Andrew Messenger and Adrian Lim and John Su and Stephen Hall and Alan Cooper and Parish, {Lawrence C} and Carrasco, {Daniel A} and McCune, {Mark A} and Werschler, {William P} and Belasco, {Kevin T} and Abe Marcadis and Gardner, {Timothy L} and Guenthner, {Scott T} and Nelson, {Christopher G} and Ben Barankin and Lorne Albrecht and Melinda Gooderham and Yves Poulin and Leslie Rosoph and Gauthier, {Jean Sebastien} and Ronald Vender and Norman Wasel and Shireen Sidhu and Diana Rubel and Peter Foley and Lynda Spelman and Isaac Bodokh and Anne-Benedicte Duval-Modeste and Gerard Guillet and Carle Paul and Jean-Philippe Lacour and Francois Aubin and Guillaume Chaby and Jean-Jacques Grob and {Van de Kerkhof}, Peter and Amphia Ziekenhuis and {de Kort}, Wim and {Van Doorn}, {Martiin Bastiaan} and Elisabeth Riedl and Robert Strohal and Matthias Schmuth and Wolfgang Salmhofer and Benjamin Lasko and Azhar Toma and Derek Woolner and Kirk Barber and Lyn Guenther and Charles Lynde and Sam Hanna and Aditya Gupta and Rodion Kunynetz and Matthias Hoffmann and Thomas Werfel and Kristian Reich and Beate Brau and Kamran Ghoreschi and Rotraut Moessn and Petr Arenberger and Vladimir Vasku and Alena Machovcova and Carlos Ferrandiz and {Bran Eduardo}, Lopez and {Puig Sanz}, Lluis and {Herrera Ceballos}, Enrique and {Lopez Estebaranz}, Jose and {Belinchon Romero}, Isabel and Ramon Pujol and {Vanaclocha Sebastian}, Francisco and {Carretero Hernandez}, Gregorio and {Ferrandiz Pulido}, Lara and Andrew Blauvelt and Michael Bukhalo and David Stoll and Jeffrey Crowley and Yolanda Helfrich and Stephen Miller and Elyse Rafal and James Solomon and Stephen Schleicher and Joel Schlessinger and Howard Sofen and Draelos, {Zoe Diana} and Johnnie Woodson and Janna Stoessel and Hans Konig and Harald Bruning and Richard Piechatzek and Irina Lohrbacher-Kozak and Christel Contzen and Andrei Khariouzov and Peter Heymer and Kristen Kreutzmann and Hans-Michael Ockenfels and Thomas Wildfeuer and Rudolf Virchow and Uwe Reinhold and Hjalmar Kurzen and Christian Termeer and Alex Rothhaar and Peter Radny and James Coggi and Jeffrey Lenz and Kevin Kuettel and Salem Galal and Eduardo Tschen and Ruth Gilboa and Scott Fretzin and Alan Fleischer and Douglass Forsha and Theresa Knoepp and Walter Nahm and Stephanie Mehlis and Martin Menter and Paul Yamauchi and Ronald Savin and Sylke Gellrich and Bernd Kardorff and Anita R{\"u}tter and Dagmar Ludolph-Hauser and Michael Sebastian and Athanasios Tsianakas and Doerte Wolf and Wiebke Ludwig-Peitsch and Sandra Philipp and Mathias Augustin and Rumyana Yankova and Jana Kazandjieva and Iliya Tsingov and Tzetza Vlaeva and Neil Sadick and Joseph Fowler and Artis Truett and Jashin Wu and Michael Bernhardt and Mark Lee and Jerry Bagel and Frederick Behringer and Leon Kircik and Javier Alonso-Llamazares and Susan Hole and Phoebe Rich and Kenneth Gordon and James Campbell and Miroslava Kadurina and Maria Poznanska and Lidia Rajzer and Kamila Padlewska and {Gonzalez Soto}, {Remigio F} and Gonzalez, {Javier A} and Lajos Kemeny and Eva Remenyik and Zsuzsanna Karolyi and Noemi Bakos and Edina Nemes and Levente Kovago and Eniko Telegdy and Kristina Callis-Duffin and Alice Gottlieb and Jennifer Soung and April Armstrong and David Norris and Richard Thomas and Stewart Adams and Kim Papp and Richard Langley and Isabelle Delorme and Michael Robern and Youwen Zhou and Jerry Tan and Mani Raman and Shakti Sharma and Catherine Maari and Rolland Gyulai and Dalma Varszegi and Ivan Orojan and Dosa Piroska and Ildiko Vincze and Eva Melegh and Krylatskie Cholmy and Perlamutrov, {Yuriy N} and Krasnodarskiy Kray and Nikolay Murashkin and Alexey Sukharev and Anton Edin and Yana Smirnova and Kirill Rudinskiy and Georg Popp and Wolfgang Vanscheidt and Fachbereich Medizin and Johann Wolfgang and Roland Kaufmann and Diamant Thaci and Sandrine Benoit and Andrea Thron and Petra Kast and Klinische Studien and Martin Kaatz and Rudolf Schopf and Elisabeth Theis and Christine Paschen and Liebhild Stratmann and Andrea Graefe and Kristin Kreutzmann and Elizaveta Degtyareva and Konstantin Raznatovskiy and Olga Stetsiouk and Stanislav Givirovskiy and Petr Chizhov and Fernando Valenzuela and [Unknown] Fernandez and Pablo Gonzalez and Galimberti, {Ricardo Luis} and Magarinos, {Gabriel Alejandro}",

year = "2015",

month = aug,

day = "8",

doi = "10.1016/S0140-6736(15)60125-8",

language = "English",

volume = "386",

pages = "541--551",

journal = "Lancet (London, England)",

issn = "1474-547X",

publisher = "Elsevier BV",

number = "9993",

}

Griffiths, CEM, Lebwohl, M, van de Kerkhof, P, Menter, A, Cameron, GS, Erickson, J, Zhang, L, Secrest, RJ, Ball, S, Braun, DK, Osuntokun, OO, Heffernan, MP, Nickoloff, BJ, Kerr, DJ, Birbara, C, Ko, WT, Koltun, WD, Dosik, JS, Lewis, D, Ehrlich, A, Strober, BE, George, RE, Gillum, P, Hamilton, TK, Hoekstra, JA, Abramovits, W, Lebwohl, MG, Lee, PC, Podda, M, Rieken, T, Grigat, C, Norgauer, J, Carus, CG, Wozel, G, Koerber, A, Rosenbach, T, Chodorowska, G, Maleszka, R, Kaszuba, A, Rudnicka, L, Szymanska, EB, Klujszo, E, Nowicki, R, Wasik, G, Thorla, IH, Moore, A, Grande, K, Sobell, JM, Lockshin, B, Humeniuk, JM, Rankin, BG, Delamo, JG, Pariser, DM, Leonardi, CL, Davis, SA, Ferris, LK, Rendon, MI, Weisman, JD, Fromowitz, JS, Jazayeri, SS, Nossa, R, Solovan, C, Mihalache, D, Tiplica, G-S, Zbranca-Toporas, A, Florea, I, Beti, H, Wainwright, N, Griffiths, C, McBride, S, Burden, D, Foerster, J, Butt, A, Messenger, A, Lim, A, Su, J, Hall, S, Cooper, A, Parish, LC, Carrasco, DA, McCune, MA, Werschler, WP, Belasco, KT, Marcadis, A, Gardner, TL, Guenthner, ST, Nelson, CG, Barankin, B, Albrecht, L, Gooderham, M, Poulin, Y, Rosoph, L, Gauthier, JS, Vender, R, Wasel, N, Sidhu, S, Rubel, D, Foley, P, Spelman, L, Bodokh, I, Duval-Modeste, A-B, Guillet, G, Paul, C, Lacour, J-P, Aubin, F, Chaby, G, Grob, J-J, Van de Kerkhof, P, Ziekenhuis, A, de Kort, W, Van Doorn, MB, Riedl, E, Strohal, R, Schmuth, M, Salmhofer, W, Lasko, B, Toma, A, Woolner, D, Barber, K, Guenther, L, Lynde, C, Hanna, S, Gupta, A, Kunynetz, R, Hoffmann, M, Werfel, T, Reich, K, Brau, B, Ghoreschi, K, Moessn, R, Arenberger, P, Vasku, V, Machovcova, A, Ferrandiz, C, Bran Eduardo, L, Puig Sanz, L, Herrera Ceballos, E, Lopez Estebaranz, J, Belinchon Romero, I, Pujol, R, Vanaclocha Sebastian, F, Carretero Hernandez, G, Ferrandiz Pulido, L, Blauvelt, A, Bukhalo, M, Stoll, D, Crowley, J, Helfrich, Y, Miller, S, Rafal, E, Solomon, J, Schleicher, S, Schlessinger, J, Sofen, H, Draelos, ZD, Woodson, J, Stoessel, J, Konig, H, Bruning, H, Piechatzek, R, Lohrbacher-Kozak, I, Contzen, C, Khariouzov, A, Heymer, P, Kreutzmann, K, Ockenfels, H-M, Wildfeuer, T, Virchow, R, Reinhold, U, Kurzen, H, Termeer, C, Rothhaar, A, Radny, P, Coggi, J, Lenz, J, Kuettel, K, Galal, S, Tschen, E, Gilboa, R, Fretzin, S, Fleischer, A, Forsha, D, Knoepp, T, Nahm, W, Mehlis, S, Menter, M, Yamauchi, P, Savin, R, Gellrich, S, Kardorff, B, Rütter, A, Ludolph-Hauser, D, Sebastian, M, Tsianakas, A, Wolf, D, Ludwig-Peitsch, W, Philipp, S, Augustin, M, Yankova, R, Kazandjieva, J, Tsingov, I, Vlaeva, T, Sadick, N, Fowler, J, Truett, A, Wu, J, Bernhardt, M, Lee, M, Bagel, J, Behringer, F, Kircik, L, Alonso-Llamazares, J, Hole, S, Rich, P, Gordon, K, Campbell, J, Kadurina, M, Poznanska, M, Rajzer, L, Padlewska, K, Gonzalez Soto, RF, Gonzalez, JA, Kemeny, L, Remenyik, E, Karolyi, Z, Bakos, N, Nemes, E, Kovago, L, Telegdy, E, Callis-Duffin, K, Gottlieb, A, Soung, J, Armstrong, A, Norris, D, Thomas, R, Adams, S, Papp, K, Langley, R, Delorme, I, Robern, M, Zhou, Y, Tan, J, Raman, M, Sharma, S, Maari, C, Gyulai, R, Varszegi, D, Orojan, I, Piroska, D, Vincze, I, Melegh, E, Cholmy, K, Perlamutrov, YN, Kray, K, Murashkin, N, Sukharev, A, Edin, A, Smirnova, Y, Rudinskiy, K, Popp, G, Vanscheidt, W, Medizin, F, Wolfgang, J, Kaufmann, R, Thaci, D, Benoit, S, Thron, A, Kast, P, Studien, K, Kaatz, M, Schopf, R, Theis, E, Paschen, C, Stratmann, L, Graefe, A, Kreutzmann, K, Degtyareva, E, Raznatovskiy, K, Stetsiouk, O, Givirovskiy, S, Chizhov, P, Valenzuela, F, Fernandez, U, Gonzalez, P, Galimberti, RL & Magarinos, GA 2015, 'Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.', Lancet (London, England), vol. 386, no. 9993, pp. 541-551. https://doi.org/10.1016/S0140-6736(15)60125-8

TY - JOUR

T1 - Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.

AU - Griffiths, CEM

AU - Lebwohl, Mark

AU - van de Kerkhof, Peter

AU - Menter, Alan

AU - Cameron, Gregory S

AU - Erickson, Janelle

AU - Zhang, Lu

AU - Secrest, Roberta J

AU - Ball, Susan

AU - Braun, Daniel K

AU - Osuntokun, Olawale O

AU - Heffernan, Michael P

AU - Nickoloff, Brian J

A2 - Kerr, David J

A2 - Birbara, Charles

A2 - Ko, William T

A2 - Koltun, William D

A2 - Dosik, Jonathan S

A2 - Lewis, Derek

A2 - Ehrlich, Alison

A2 - Strober, Bruce E

A2 - George, Rosalyn E

A2 - Gillum, Paul

A2 - Hamilton, Tiffani K

A2 - Hoekstra, John A

A2 - Abramovits, William

A2 - Lebwohl, Mark G

A2 - Lee, Patricia C

A2 - Podda, Maurizio

A2 - Rieken, Tilmann

A2 - Grigat, Christine

A2 - Norgauer, Johannes

A2 - Carus, Carl Gustav

A2 - Wozel, Gottfried

A2 - Koerber, Andreas

A2 - Rosenbach, Thomas

A2 - Chodorowska, Grazyna

A2 - Maleszka, Romuald

A2 - Kaszuba, Andrzej

A2 - Rudnicka, Lidia

A2 - Szymanska, Elzbieta B

A2 - Klujszo, Elzbieta

A2 - Nowicki, Roman

A2 - Wasik, Grazyna

A2 - Thorla, Ira H

A2 - Moore, Angela

A2 - Grande, Kimberly

A2 - Sobell, Jeffrey M

A2 - Lockshin, Benjamin

A2 - Humeniuk, John M

A2 - Rankin, Bruce G

A2 - Delamo, Joseph G

A2 - Pariser, David M

A2 - Leonardi, Craig L

A2 - Davis, Steven A

A2 - Ferris, Laura K

A2 - Rendon, Marta I

A2 - Weisman, Jamie D

A2 - Fromowitz, Jeffrey S

A2 - Jazayeri, S Sasha

A2 - Nossa, Robert

A2 - Solovan, Caius

A2 - Mihalache, Dorin

A2 - Tiplica, George-Sorin

A2 - Zbranca-Toporas, Anca

A2 - Florea, Ion

A2 - Beti, Horia

A2 - Wainwright, Nicholas

A2 - Griffiths, Christopher

A2 - McBride, Sandy

A2 - Burden, David

A2 - Foerster, John

A2 - Butt, Aamir

A2 - Messenger, Andrew

A2 - Lim, Adrian

A2 - Su, John

A2 - Hall, Stephen

A2 - Cooper, Alan

A2 - Parish, Lawrence C

A2 - Carrasco, Daniel A

A2 - McCune, Mark A

A2 - Werschler, William P

A2 - Belasco, Kevin T

A2 - Marcadis, Abe

A2 - Gardner, Timothy L

A2 - Guenthner, Scott T

A2 - Nelson, Christopher G

A2 - Barankin, Ben

A2 - Albrecht, Lorne

A2 - Gooderham, Melinda

A2 - Poulin, Yves

A2 - Rosoph, Leslie

A2 - Gauthier, Jean Sebastien

A2 - Vender, Ronald

A2 - Wasel, Norman

A2 - Sidhu, Shireen

A2 - Rubel, Diana

A2 - Foley, Peter

A2 - Spelman, Lynda

A2 - Bodokh, Isaac

A2 - Duval-Modeste, Anne-Benedicte

A2 - Guillet, Gerard

A2 - Paul, Carle

A2 - Lacour, Jean-Philippe

A2 - Aubin, Francois

A2 - Chaby, Guillaume

A2 - Grob, Jean-Jacques

A2 - Van de Kerkhof, Peter

A2 - Ziekenhuis, Amphia

A2 - de Kort, Wim

A2 - Van Doorn, Martiin Bastiaan

A2 - Riedl, Elisabeth

A2 - Strohal, Robert

A2 - Schmuth, Matthias

A2 - Salmhofer, Wolfgang

A2 - Lasko, Benjamin

A2 - Toma, Azhar

A2 - Woolner, Derek

A2 - Barber, Kirk

A2 - Guenther, Lyn

A2 - Lynde, Charles

A2 - Hanna, Sam

A2 - Gupta, Aditya

A2 - Kunynetz, Rodion

A2 - Hoffmann, Matthias

A2 - Werfel, Thomas

A2 - Reich, Kristian

A2 - Brau, Beate

A2 - Ghoreschi, Kamran

A2 - Moessn, Rotraut

A2 - Arenberger, Petr

A2 - Vasku, Vladimir

A2 - Machovcova, Alena

A2 - Ferrandiz, Carlos

A2 - Bran Eduardo, Lopez

A2 - Puig Sanz, Lluis

A2 - Herrera Ceballos, Enrique

A2 - Lopez Estebaranz, Jose

A2 - Belinchon Romero, Isabel

A2 - Pujol, Ramon

A2 - Vanaclocha Sebastian, Francisco

A2 - Carretero Hernandez, Gregorio

A2 - Ferrandiz Pulido, Lara

A2 - Blauvelt, Andrew

A2 - Bukhalo, Michael

A2 - Stoll, David

A2 - Crowley, Jeffrey

A2 - Helfrich, Yolanda

A2 - Miller, Stephen

A2 - Rafal, Elyse

A2 - Solomon, James

A2 - Schleicher, Stephen

A2 - Schlessinger, Joel

A2 - Sofen, Howard

A2 - Draelos, Zoe Diana

A2 - Woodson, Johnnie

A2 - Stoessel, Janna

A2 - Konig, Hans

A2 - Bruning, Harald

A2 - Piechatzek, Richard

A2 - Lohrbacher-Kozak, Irina

A2 - Contzen, Christel

A2 - Khariouzov, Andrei

A2 - Heymer, Peter

A2 - Kreutzmann, Kristen

A2 - Ockenfels, Hans-Michael

A2 - Wildfeuer, Thomas

A2 - Virchow, Rudolf

A2 - Reinhold, Uwe

A2 - Kurzen, Hjalmar

A2 - Termeer, Christian

A2 - Rothhaar, Alex

A2 - Radny, Peter

A2 - Coggi, James

A2 - Lenz, Jeffrey

A2 - Kuettel, Kevin

A2 - Galal, Salem

A2 - Tschen, Eduardo

A2 - Gilboa, Ruth

A2 - Fretzin, Scott

A2 - Fleischer, Alan

A2 - Forsha, Douglass

A2 - Knoepp, Theresa

A2 - Nahm, Walter

A2 - Mehlis, Stephanie

A2 - Menter, Martin

A2 - Yamauchi, Paul

A2 - Savin, Ronald

A2 - Gellrich, Sylke

A2 - Kardorff, Bernd

A2 - Rütter, Anita

A2 - Ludolph-Hauser, Dagmar

A2 - Sebastian, Michael

A2 - Tsianakas, Athanasios

A2 - Wolf, Doerte

A2 - Ludwig-Peitsch, Wiebke

A2 - Philipp, Sandra

A2 - Augustin, Mathias

A2 - Yankova, Rumyana

A2 - Kazandjieva, Jana

A2 - Tsingov, Iliya

A2 - Vlaeva, Tzetza

A2 - Sadick, Neil

A2 - Fowler, Joseph

A2 - Truett, Artis

A2 - Wu, Jashin

A2 - Bernhardt, Michael

A2 - Lee, Mark

A2 - Bagel, Jerry

A2 - Behringer, Frederick

A2 - Kircik, Leon

A2 - Alonso-Llamazares, Javier

A2 - Hole, Susan

A2 - Rich, Phoebe

A2 - Gordon, Kenneth

A2 - Campbell, James

A2 - Kadurina, Miroslava

A2 - Poznanska, Maria

A2 - Rajzer, Lidia

A2 - Padlewska, Kamila

A2 - Gonzalez Soto, Remigio F

A2 - Gonzalez, Javier A

A2 - Kemeny, Lajos

A2 - Remenyik, Eva

A2 - Karolyi, Zsuzsanna

A2 - Bakos, Noemi

A2 - Nemes, Edina

A2 - Kovago, Levente

A2 - Telegdy, Eniko

A2 - Callis-Duffin, Kristina

A2 - Gottlieb, Alice

A2 - Soung, Jennifer

A2 - Armstrong, April

A2 - Norris, David

A2 - Thomas, Richard

A2 - Adams, Stewart

A2 - Papp, Kim

A2 - Langley, Richard

A2 - Delorme, Isabelle

A2 - Robern, Michael

A2 - Zhou, Youwen

A2 - Tan, Jerry

A2 - Raman, Mani

A2 - Sharma, Shakti

A2 - Maari, Catherine

A2 - Gyulai, Rolland

A2 - Varszegi, Dalma

A2 - Orojan, Ivan

A2 - Piroska, Dosa

A2 - Vincze, Ildiko

A2 - Melegh, Eva

A2 - Cholmy, Krylatskie

A2 - Perlamutrov, Yuriy N

A2 - Kray, Krasnodarskiy

A2 - Murashkin, Nikolay

A2 - Sukharev, Alexey

A2 - Edin, Anton

A2 - Smirnova, Yana

A2 - Rudinskiy, Kirill

A2 - Popp, Georg

A2 - Vanscheidt, Wolfgang

A2 - Medizin, Fachbereich

A2 - Wolfgang, Johann

A2 - Kaufmann, Roland

A2 - Thaci, Diamant

A2 - Benoit, Sandrine

A2 - Thron, Andrea

A2 - Kast, Petra

A2 - Studien, Klinische

A2 - Kaatz, Martin

A2 - Schopf, Rudolf

A2 - Theis, Elisabeth

A2 - Paschen, Christine

A2 - Stratmann, Liebhild

A2 - Graefe, Andrea

A2 - Kreutzmann, Kristin

A2 - Degtyareva, Elizaveta

A2 - Raznatovskiy, Konstantin

A2 - Stetsiouk, Olga

A2 - Givirovskiy, Stanislav

A2 - Chizhov, Petr

A2 - Valenzuela, Fernando

A2 - Fernandez, [Unknown]

A2 - Gonzalez, Pablo

A2 - Galimberti, Ricardo Luis

A2 - Magarinos, Gabriel Alejandro

PY - 2015/8/8

Y1 - 2015/8/8

N2 - BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9-91·8) vs placebo; 48·1% (41·2-55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4-85·7) vs placebo; 33·9% (27·0-40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5-80·8) vs placebo; 35·9% (28·2-43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0-82·8) vs placebo; 30·8% (23·7-37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p

AB - BACKGROUND: Ixekizumab is a humanised monoclonal antibody against the proinflammatory cytokine interleukin 17A. We report two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis. METHODS: In two prospective, double-blind, multicentre, phase 3 studies (UNCOVER-2 and UNCOVER-3), eligible patients were aged 18 years or older, had a confirmed diagnosis of chronic plaque psoriasis at least 6 months before baseline (randomisation), 10% or greater body-surface area involvement at both screening and baseline visits, at least a moderate clinical severity as measured by a static physician global assessment (sPGA) score of 3 or more, and a psoriasis area and severity index (PASI) score of 12. Participants were randomly assigned (1:2:2:2) by computer-generated random sequence with an interactive voice response system to receive subcutaneous placebo, etanercept (50 mg twice weekly), or one injection of 80 mg ixekizumab every 2 weeks, or every 4 weeks after a 160 mg starting dose. Blinding was maintained with a double-dummy design. Coprimary efficacy endpoints were proportions of patients achieving sPGA score 0 or 1 and 75% or greater improvement in PASI at week 12. Analysis was by intention to treat. These trials are registered with ClinicalTrials.gov, numbers NCT01597245 and NCT01646177. FINDINGS: Between May 30, 2012, and Dec 30, 2013, 1224 patients in UNCOVER-2 were randomly assigned to receive subcutaneous placebo (n=168), etanercept (n=358), or ixekizumab every 2 weeks (n=351) or every 4 weeks (n=347); between Aug 11, 2012, and Feb 27, 2014, 1346 patients in UNCOVER-3 were randomly assigned to receive placebo (n=193), etanercept (n=382), ixekizumab every 2 weeks (n=385), or ixekizumab every 4 weeks (n=386). At week 12, both primary endpoints were met in both studies. For UNCOVER-2 and UNCOVER-3 respectively, in the ixekizumab every 2 weeks group, PASI 75 was achieved by 315 (response rate 89·7%; [effect size 87·4% (97·5% CI 82·9-91·8) vs placebo; 48·1% (41·2-55·0) vs etanercept]) and 336 (87·3%; [80·0% (74·4-85·7) vs placebo; 33·9% (27·0-40·7) vs etanercept]) patients; in the ixekizumab every 4 weeks group, by 269 (77·5%; [75·1% (69·5-80·8) vs placebo; 35·9% (28·2-43·6) vs etanercept]) and 325 (84·2%; [76·9% (71·0-82·8) vs placebo; 30·8% (23·7-37·9) vs etanercept]) patients; in the placebo group, by four (2·4%) and 14 (7·3%) patients; and in the etanercept group by 149 (41·6%) and 204 (53·4%) patients (all p

U2 - 10.1016/S0140-6736(15)60125-8

DO - 10.1016/S0140-6736(15)60125-8

M3 - Article

C2 - 26072109

SN - 1474-547X

VL - 386

SP - 541

EP - 551

JO - Lancet (London, England)

JF - Lancet (London, England)

IS - 9993

ER -

Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials.

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