TY - JOUR

T1 - Efficacy and safety of ustekinumab in patients with active psoriatic arthritis

T2 - 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial

AU - McInnes, Iain B.

AU - Kavanaugh, Arthur

AU - Gottlieb, Alice B.

AU - Puig, Lluís

AU - Rahman, Proton

AU - Ritchlin, Christopher

AU - Brodmerkel, Carrie

AU - Li, Shu

AU - Wang, Yuhua

AU - Mendelsohn, Alan M.

AU - Doyle, Mittie K.

AU - Aelion, Jacob

AU - Akovbyan, Gaspar

AU - Andersone, Daina

AU - Bakulev, Audrey

AU - Basijokiene, Vida

AU - Beaulieu, Andre

AU - Birbara, Charles

AU - Boh, Erin

AU - Bourcier, Marc

AU - Braun, Jurgen

AU - Brzezicki, Jan

AU - Buchanan, Russell

AU - Budd, John

AU - Bukauskiene, Loreta

AU - Burnette, Michael

AU - Crespillo, Juan Canete

AU - Carey, Wayne

AU - Chattapadhyay, Chandra

AU - Chudzik, Dariusz

AU - Cooper, Robert

AU - Drescher, Edit

AU - Dudek, Anna

AU - Dutz, Jan

AU - El-Kadi, Hisham

AU - Erlacher, Ludwig

AU - Fretzin, Scott A.

AU - Garcia Meijide, Juan A.

AU - George, Emmanuel

AU - Gilchrist, Nigel

AU - Gladstein, Geoffrey

AU - Gow, Peter

AU - Graninger, Winfried

AU - Griffin, Robert M.

AU - Guenther, Lyn

AU - Gulliver, Wayne

AU - Hall, Stephen

AU - Halter, Dale G.

AU - Hobbs, Kathryn

AU - Ilivanova, Elana

AU - Jarvinen, Pentti

AU - Jeka, Slawomir

AU - Jones, Peter

AU - Khraishi, Majed

AU - Kokhan, Muza

AU - Kovacs, Attila

AU - Kovacs, Laszlo

AU - Kubanov, Alexey

AU - Kunynetz, Rod

AU - Langley, Richard

AU - Lee, Susan

AU - Leonardi, Craig L.

AU - Lessard, Clode

AU - Lietuvininkiene, Virginija

AU - Lizzul, Paul

AU - Martin, Alan

AU - Maslyanskiy, Alexey

AU - Matheson, Robert T.

AU - Mikazane, Helene

AU - Murphy, Frederick T.

AU - Nash, Peter

AU - Nasonov, Eugeny

AU - Sarabia, Frederico Navarro

AU - Orlov-Morozov, Alexander

AU - Paimela, Leena

AU - Palmer, William

AU - Papp, Kim

AU - Pileckyte, Margarita

AU - Poor, Gyula

AU - Poulin, Yves

AU - Silva, Ruben Queiro

AU - Rapoport, Ronald

AU - Rebrov, Audrey

AU - Rell-Bakalarska, Maria

AU - Rich, Phoebe

AU - Rischmueller, Maureen

AU - Rojkovich, Bernadette

AU - Rosen, Cheryl

AU - Rosoph, Les

AU - Scheinecker, Clemens

AU - Schopf, Rudolph

AU - Sebastian, Michael

AU - Seigel, Stuart

AU - Shaikh, Saeed

AU - Sheeran, Tom

AU - Shergy, William J.

AU - Shirinsky, Valery

AU - Siegel, Evan L.

AU - Sofen, Howard

AU - Sterry, Wolfram

AU - Supronik, Jerzy

AU - Szabo, Zoltan

AU - Szanyo, Ferenc

AU - Tahir, Hasan

AU - Tan, Jerry

AU - Taylor, William

AU - Temnikov, Vadim

AU - Thaci, Diamant

AU - Toth, Darryl

AU - Újfalussy, Ilona

AU - Valleala, Heikki

AU - Vender, Ronald

AU - Wasel, Norman

AU - Willans, Martin

AU - Wollenhaupt, Jurgen

AU - Zamani, Omid

AU - Zanetakis, Ellen

AU - Zonova, Elena

AU - Zoschke, David

AU - Zubrzycka-Sienkiewicz, Anna

N1 - Funding Information: This study was funded by Janssen Research & Development. We thank Michelle Perate, a paid consultant for Janssen Services; Mary Whitman, an employee of Janssen Services, for writing and editorial support; and Lisa T Dooley, an employee of Janssen Research & Development, for statistical support.

PY - 2013

Y1 - 2013

N2 - Background Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. Methods In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). Findings Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). Interpretation Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. Funding Janssen Research & Development.

AB - Background Many patients with psoriasis develop psoriatic arthritis, a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures. The fully human monoclonal antibody ustekinumab is an efficacious treatment for moderate-to-severe plaque psoriasis. We did a randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis. Methods In this phase 3, multicentre, double-blind, placebo-controlled trial at 104 sites in Europe, North America, and Asia-Pacific, adults with active psoriatic arthritis (≥5 tender and ≥5 swollen joints, C-reactive protein ≥3·0 mg/L) were randomly assigned (1:1:1, by dynamic central randomisation based on an algorithm implemented by an interactive voice-web response system) to 45 mg ustekinumab, 90 mg ustekinumab, or placebo at week 0, week 4, and every 12 weeks thereafter. At week 16, patients with less than 5% improvement in both tender and swollen joint counts entered masked early-escape and were given 45 mg ustekinumab (if in the placebo group) or 90 mg ustekinumab (if in the 45 mg group). At week 24, all remaining patients in the placebo group received ustekinumab 45 mg, which they continued at week 28 and every 12 weeks thereafter. Our primary endpoint was 20% or greater improvement in American College of Rheumatology (ACR20) criteria at week 24. This trial is registered with ClinicalTrials.gov (NCT01009086) and EudraCT (2009-012264-14). Findings Between Nov 30, 2009, and March 30, 2011, 615 patients were randomly assigned-206 to placebo, 205 to 45 mg ustekinumab, and 204 to 90 mg ustekinumab. More ustekinumab-treated (87 of 205 [42·4%] in the 45 mg group and 101 of 204 [49·5%] in the 90 mg group) than placebo-treated (47 of 206 [22·8%]) patients achieved ACR20 at week 24 (p<0·0001 for both comparisons); responses were maintained at week 52. At week 16, proportions of patients with adverse events were similar in the ustekinumab and placebo groups (171 of 409 [41·8%] vs 86 of 205 [42·0%]). Interpretation Ustekinumab significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. Funding Janssen Research & Development.

UR - http://www.scopus.com/inward/record.url?scp=84883134297&partnerID=8YFLogxK

U2 - 10.1016/S0140-6736(13)60594-2

DO - 10.1016/S0140-6736(13)60594-2

M3 - Article

C2 - 23769296

AN - SCOPUS:84883134297

VL - 382

SP - 780

EP - 789

JO - The Lancet

JF - The Lancet

SN - 0140-6736

IS - 9894

ER -