ArticlesEfficacy 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
Introduction
Psoriatic arthritis is a chronic inflammatory disease that afflicts peripheral synovial, axial, and entheseal structures and is associated with skin psoriasis and nail involvement.1 Substantial proportions of patients with psoriasis develop psoriatic arthritis,2, 3 which is associated with reduced quality of life, several comorbidities, and increased mortality.4, 5, 6, 7, 8, 9
Conventional treatment for psoriatic arthritis usually begins with disease-modifying antirheumatic drugs and non-steroidal anti-inflammatory drugs, followed by tumour necrosis factor α (TNFα) inhibitors when necessary. T-helper-17 (Th17) cells are postulated to have a major role in psoriatic inflammation, and thus various biological drugs directed against interleukins 17 and 23 are being investigated.10, 11, 12, 13, 14, 15
Ustekinumab is a fully human IgG 1κ monoclonal antibody that binds to the common p40 subunit shared by interleukins 12 and 23. Efficacy against plaque psoriasis and an acceptable safety profile have been shown in large phase 3 trials,12, 13, 14 and the drug is approved for use in the treatment of moderate-to-severe psoriasis. In a phase 2 trial15 of patients with active psoriatic arthritis, ustekinumab significantly improved signs and symptoms of psoriatic arthritis and improved quality of life compared with placebo. Thus, we did the phase 3, placebo-controlled PSUMMIT 1 trial to further assess the safety and efficacy of ustekinumab in patients with active psoriatic arthritis.
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Study design and participants
PSUMMIT 1 was a phase 3, randomised, placebo-controlled trial at 104 sites in 14 countries—specifically, Australia, Austria, Canada, Finland, Germany, Hungary, Latvia, Lithuania, New Zealand, Poland, Russia, Spain, the UK, and the USA. Patients were recruited by individual study sites via clinics, outside referrals, and advertisements. Patients were screened and randomly assigned between Nov 30, 2009, and March 30, 2011. The week 52 database was locked on July 12, 2012. The trial continues, and
Results
1174 patients were screened, 615 of whom were randomly assigned (figure 1). Most of the patients who were not randomly assigned did not meet the inclusion criteria of five or more swollen and tender joints at screening and baseline and CRP concentrations of 3·0 mg/L or more at screening. 397 patients were randomly assigned at European sites, 175 at North American sites, and 43 at Asia-Pacific sites. 78 (12·7%) patients discontinued study agent by week 52 (figure 1).
The study population
Discussion
In this multicentre, phase 3, double-blind, placebo-controlled trial, subcutaneous ustekinumab was effective and well tolerated in patients with active psoriatic arthritis at week 52 (panel). ACR20 responses were significantly higher in ustekinumab-treated than in placebo-treated patients at week 24, and thus we met our primary study endpoint. We noted differences in efficacy by weeks 4–8. Data about the effects of ustekinumab on radiographic progression are forthcoming.
The highest ACR20
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These authors contributed equally