Two studies in this week's edition of The Lancet have shown the efficacy of ustekinumab for treating moderate-to-severe psoriasis, and that dosing every 12 weeks maintains efficacy in most patients. Psoriasis is the most common immune-mediated skin disease in adults, with an estimated prevalence of 2-3%. Interleukins* 12 and 23 are believed to have a central role in psoriasis physiology, and agents that block these interleukins have shown promise as drugs for treating psoriasis; however, currently available therapeutic options have left a substantial unmet need for treatments that are convenient, effective, and well tolerated, especially for long term treatment.
The PHOENIX studies have been carried out by two teams of investigators to determine the efficacy of ustekinumab, a drug which binds to interleukins 12 and 23 and prevents their interaction with their specific receptors on the surface of cells. Dr Kenneth Gordon, Northwestern University, Feinburg School of Medicine and Evanston Northwestern Healthcare, Evanston, IL, USA and colleagues did the PHOENIX I trial. In this study, 766 patients with moderate-to-severe psoriasis were randomly assigned to received ustekinumab 45mg (255 patients) or 90mg (256) at weeks 0 and 4 and then every 12 weeks; or placebo (255) at weeks 0 and 4, with subsequent crossover to ustekinumab at week 12. Patients who were initially randomised to receive ustekinumab who achieved long-term response (at least 75% improvement in psoriasis areas and severity index [PASI 75] at weeks 28 and 40) were re-randomised at week 40 to maintenance ustekinumab or withdrawal from treatment until loss of response. The primary endpoint of the trials was proportion of patients achieving PASI 75 at week 12.
The researchers found that 171 (67%) of patients receiving ustekinumab 45mg, 170 (66%) receiving ustekinumab 90mg, and eight (3.1%) receiving placebo achieved PASI 75 at week 12. At week 40, long-term response had been achieved by 150 patients in the 45mg group, and 172 in the 90mg group. Following this, 162 patients were randomly assigned to maintenance ustekinumab and 160 to withdrawal. PASI 75 response was better maintained to at least 1 year in the those given maintenance treatment. Rates of adverse events were similar between ustekinumab and placebo groups.
The authors conclude: "Our results suggest that ustekinumab could be an important therapeutic agent for treating patients with psoriasis¡.The high level of efficacy was generally maintained with dosing every 12 weeks, a schedule that could offer a novel level of convenience for patients and physicians."
The PHOENIX 2 study was done by Dr Kim Papp, Probity Medical Research Inc, Waterloo, ON, Canada, and colleagues. In this trial, 1230 patients with moderate-to-severe psoriasis (defined by a psoriasis area and severity index [PASI] score ¡Ý12, and at least 10% total body surface area involvement) were randomly assigned to receive ustekinumab 45mg (409 patients) or 90mg (411) at weeks 0 and 4, then every 12 weeks, or placebo (410). Partial responders (ie, patients achieving ¡Ý50% but <75% improvement from baseline in PASI) were re-randomised at week 28 to continue dosing every 12 weeks or escalate to dosing every eight weeks. Again the primary endpoint was the proportion of patients achieving at least 75% improvement in PASI 75 at week 12.
The researchers found that 273 (67%) of patients receiving ustekinumab 45mg, 311 (76%) receiving ustekinumab 90mg, and 15 (4%) of patients receiving placebo achieved PASI 75 at week 12. The proportion of partial responders at week 28 who received ustekinumab 90mg every 8 weeks and achieved PASI 75 (69%) was more than double the proportion who continued on the same dose every 12 weeks (33%). There was no such response change in partial responders given ustekinumab 45mg every eight weeks. Again adverse events were similar between ustekinumab and placebo groups.
The authors conclude: "Although treatment with ustekinumab every 12 weeks is effective for most patients with moderate-to-severe psoriasis, intensification of dosing to once every eight weeks with ustekinumab 90mg might be necessary to elicit a full response in patients who only partially respond to the initial regimen."
In an accompanying Comment, Dr Brenda Bartlett and Professor Stephen Tyring, University of Texas Health Science Center, Houston, TX, USA, say: "Not only does ustekinumab compare favourably to the best available therapies for psoriasis, the maintenance of response between injections every three months also provides a more convenient regimen than those currently available."
Notes to editors: *Interleukins: Proteins produced by the immune system that mediate inflammatory reactions in diseases like psoriasis.
For Dr Kenneth Gordon, Evanston Northwestern Healthcare, Evanston, IL, USA, please contact Rikki Ragland, T) +1 847.570.3144 E) KGordon@enh.org / RRagland@enh.org
Dr Kim Papp, Probity Medical Reseach, Waterloo, Ontario, Canada T) +1 519 579 9535 E) kapapp@probitymedical.com
Professor Stephen Tyring, University of Texas Health Science Center, Houston, TX, USA T) +1 281-773-9317 E) styring@ccstexas.com
http://multimedia.thelancet.com/pdf/press/phoenix.pdf
Journal
The Lancet