Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial

Iain B. McInnes, Arthur Kavanaugh, Alice B. Gottlieb, Lluís Puig, Proton Rahman, Christopher Ritchlin, Carrie Brodmerkel, Shu Li, Yuhua Wang, Alan M. Mendelsohn, Mittie K. Doyle, Jacob Aelion, Gaspar Akovbyan, Daina Andersone, Audrey Bakulev, Vida Basijokiene, Andre Beaulieu, Charles Birbara, Erin Boh, Marc BourcierJurgen Braun, Jan Brzezicki, Russell Buchanan, John Budd, Loreta Bukauskiene, Michael Burnette, Juan Canete Crespillo, Wayne Carey, Chandra Chattapadhyay, Dariusz Chudzik, Robert Cooper, Edit Drescher, Anna Dudek, Jan Dutz, Hisham El-Kadi, Ludwig Erlacher, Scott A. Fretzin, Juan A. Garcia Meijide, Emmanuel George, Nigel Gilchrist, Geoffrey Gladstein, Peter Gow, Winfried Graninger, Robert M. Griffin, Lyn Guenther, Wayne Gulliver, Stephen Hall, Dale G. Halter, Kathryn Hobbs, Elana Ilivanova, Pentti Jarvinen, Slawomir Jeka, Peter Jones, Majed Khraishi, Muza Kokhan, Attila Kovacs, Laszlo Kovacs, Alexey Kubanov, Rod Kunynetz, Richard Langley, Susan Lee, Craig L. Leonardi, Clode Lessard, Virginija Lietuvininkiene, Paul Lizzul, Alan Martin, Alexey Maslyanskiy, Robert T. Matheson, Helene Mikazane, Frederick T. Murphy, Peter Nash, Eugeny Nasonov, Frederico Navarro Sarabia, Alexander Orlov-Morozov, Leena Paimela, William Palmer, Kim Papp, Margarita Pileckyte, Gyula Poor, Yves Poulin, Ruben Queiro Silva, Ronald Rapoport, Audrey Rebrov, Maria Rell-Bakalarska, Phoebe Rich, Maureen Rischmueller, Bernadette Rojkovich, Cheryl Rosen, Les Rosoph, Clemens Scheinecker, Rudolph Schopf, Michael Sebastian, Stuart Seigel, Saeed Shaikh, Tom Sheeran, William J. Shergy, Valery Shirinsky, Evan L. Siegel, Howard Sofen, Wolfram Sterry, Jerzy Supronik, Zoltan Szabo, Ferenc Szanyo, Hasan Tahir, Jerry Tan, William Taylor, Vadim Temnikov, Diamant Thaci, Darryl Toth, Ilona Újfalussy, Heikki Valleala, Ronald Vender, Norman Wasel, Martin Willans, Jurgen Wollenhaupt, Omid Zamani, Ellen Zanetakis, Elena Zonova, David Zoschke, Anna Zubrzycka-Sienkiewicz

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)780-789
Number of pages10
JournalThe Lancet
Volume382
Issue number9894
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Medicine(all)

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    McInnes, I. B., Kavanaugh, A., Gottlieb, A. B., Puig, L., Rahman, P., Ritchlin, C., Brodmerkel, C., Li, S., Wang, Y., Mendelsohn, A. M., Doyle, M. K., Aelion, J., Akovbyan, G., Andersone, D., Bakulev, A., Basijokiene, V., Beaulieu, A., Birbara, C., Boh, E., ... Zubrzycka-Sienkiewicz, A. (2013). Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. The Lancet, 382(9894), 780-789. https://doi.org/10.1016/S0140-6736(13)60594-2