Fast track — ArticlesEfficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 2)
Introduction
Psoriasis is the most common immune-mediated skin disease,1, 2 with an estimated prevalence of 2–3%.3, 4 Interleukins 12 and 23 have been postulated to have a central role in psoriasis pathophysiology, and agents that block these cytokines have shown promise as therapeutic agents for the treatment of psoriasis and psoriatic arthritis.5, 6, 7, 8
Ustekinumab (CNTO 1275; Centocor Inc, Malvern, PA, USA) is a human monoclonal antibody that binds to the shared p40 subunit of interleukins 12 and 23, blocking signalling of their cognate receptors. Preclinical studies link the immune response generated by the p40 family of cytokines to psoriasis pathogenesis,9, 10 and in early clinical studies, high levels of clinical response have been seen in patients with psoriasis after treatment with ustekinumab.5, 11, 12 Although most patients achieve a clinically meaningful response,13 a subpopulation achieves only partial response. Whether residual skin disease in these partial responders is mediated by immune pathways distinct from those mediated by interleukins 12 and 23, or whether this subgroup simply requires greater exposure to ustekinumab, has not been determined.
To confirm clinical studies suggesting therapeutic potential for ustekinumab, the phase III PHOENIX 2 trial, along with PHOENIX 1,7 was designed to assess the efficacy and safety of ustekinumab in patients with moderate-to-severe psoriasis with up to 52 weeks of treatment. Additionally, PHOENIX 2 assessed whether dosing intensification would improve skin response rates in patients who partially responded to initial treatment.
Section snippets
Patients
This phase III, multicentre, double-blind, placebo-controlled trial was done at 70 sites in Europe and North America (Austria, Canada, France, Germany, Switzerland, UK, USA) between March, 2006, and September, 2007. Patients aged 18 years or older were eligible to participate if they had a diagnosis of plaque psoriasis for 6 months or longer, a baseline psoriasis area and severity index (PASI) score of 12 or higher, at least 10% body surface area involvement, and were candidates for
Results
Figure 2 shows the trial profile. Treatment groups were well balanced with regard to demographic and baseline characteristics (table 1). The mean duration of psoriasis was about 20 years, and the extent of body surface area involvement was about 25%. Most patients had used conventional systemic or biological agents to treat their psoriasis. 43 (3·5%) patients with latent tuberculosis received isoniazid during the study (table 1).
Significantly more patients in both ustekinumab groups achieved
Discussion
The results of this large phase III study, together with those of the PHOENIX 1 study,7 indicate that treatment with ustekinumab 45 mg or 90 mg results in rapid, significant improvements in patients with moderate-to-severe psoriasis. These data also lend support to the notion that interleukins 12 and 23 have a key role in the immunopathophysiology of psoriasis. Results were consistent in both trials—which together assessed almost 2000 patients—in terms of kinetics and magnitude of clinical
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