Three Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis

Arthritis and Rheumatology - Tập 71 Số 2 - Trang 258-270 - 2019
Atul Deodhar1, Lianne S. Gensler2, Joachim Sieper3, Michael B. Clark4, César Calderón4, Yuhua Wang4, Yiying Zhou4, Jocelyn H. Leu4, Kim Campbell4, Kristen Sweet4, Diane D. Harrison4, Elizabeth C. Hsia5, Désirée van der Heijde6
1Oregon Health & Science University Portland
2University of California San Francisco
3Charite Universitatsmedizin Berlin, Berlin, Germany
4Janssen Research & Development, LLC Spring House Pennsylvania
5Hospital of the University of Pennsylvania, Philadelphia
6Leiden University Medical Center, Leiden, The Netherlands.

Tóm tắt

ObjectiveTo evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo‐controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti–tumor necrosis factor [anti‐TNF]–naive patients and patients with inadequate response or intolerance to anti‐TNF, respectively); study 3 patients had nonradiographic axial SpA.MethodsIn all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo‐treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3.ResultsFor study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies.ConclusionIn these 3 placebo‐controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.

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Tài liệu tham khảo

10.1136/ard.2008.101501

10.1016/S0140-6736(16)31591-4

10.1016/j.rdc.2012.08.010

10.1002/art.1780270401

10.1136/ard.2009.108233

Cosentyx (secukinumab)[package insert]. East Hanover (NJ): Novartis Pharmaceutical;2016. URL:https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/125504s001s002lbl.pdf.

10.1007/s11926-017-0633-0

10.1136/annrheumdis-2013-204248

10.1016/j.molimm.2013.07.013

10.1038/ng.2007.17

10.1002/art.24568

10.1002/art.23655

10.1016/j.molimm.2013.07.016

10.1016/S0140-6736(08)60725-4

10.1016/S0140-6736(08)60726-6

10.1056/NEJMoa1602773

10.1002/acr.22645

10.1136/annrheumdis-2013-204741

10.1016/S0140-6736(13)60594-2

10.1136/annrheumdis-2013-204655

10.1136/annrheumdis-2015-209068

10.1136/ard.2009.110767

Garrett S, 1994, A new approach to defining disease status in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index, J Rheumatol, 21, 2286

10.1002/1529-0131(200108)44:8<1876::AID-ART326>3.0.CO;2-F

10.1136/ard.2008.104018

10.1136/ard.2011.151563

Calin A, 1994, A new approach to defining functional ability in ankylosing spondylitis: the development of the Bath Ankylosing Spondylitis Functional Index, J Rheumatol, 21, 2281

10.1136/ard.2010.138594

10.1136/ard.2003.019968

10.1136/annrheumdis-2013-204231

10.1517/14712598.2015.1084284

10.3748/wjg.v21.i19.5823

10.1016/j.jaci.2017.07.004

10.1038/s41584-018-0006-8

10.1038/nrrheum.2017.56

10.1002/art.37937

10.1186/ar3370

10.1007/s10067-008-1011-0

Romero‐Sanchez C, 2011, Association between Th‐17 cytokine profile and clinical features in patients with spondyloarthritis, Clin Exp Rheumatol, 29, 828

10.1038/nm.2817

10.1016/S0140-6736(13)61134-4

10.1016/j.immuni.2015.09.003

10.1016/j.immuni.2015.08.019

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Arthritis and Rheumatology

Tập 71 Số 2

258-270

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