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 ( Stelara ) is an efficacious treatment for moderate-to-severe plaque psoriasis.
A randomised, placebo-controlled, phase 3 trial to assess the safety and efficacy of Ustekinumab in patients with active psoriatic arthritis was conducted.
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 ( greater than or equal to 5 tender and greater than or equal to 5 swollen joints, C-reactive protein greater than or equal to 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.
The primary endpoint was 20% or greater improvement in American College of Rheumatology ( ACR20 ) criteria at week 24.
During the period 2009-2011, 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 less than 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% ] ).
In conclusion, Ustekinumab has significantly improved active psoriatic arthritis compared with placebo, and might offer an alternative therapeutic mechanism of action to approved biological treatments. ( Xagena )
McInnes IB et al, The Lancet 2013; 382: 780-789