A new treatment for moderate to severe plaque psoriasis has proven safe and effective in a phase III trial. There is also an almost linear relationship between drug dose and response, suggesting that patients can be more accurately dosed to achieve a clinical response while minimizing the risk of side-effects. These are the conclusions of authors of an Article in this week's edition of The Lancet.
Currently, one of the most effective treatments for psoriasis is the calcineurin inhibitor* ciclosporin. However, the toxic effects of this drug on the kidneys restrict its long-term use. Other, newer treatments, such as infliximab, are safe and effective for the treatment of plaque psoriasis. However, with their high cost, inconvenience of administration, and few data on long-term safety and effectiveness, their widespread use might not be possible.
Dr Kim Papp, Probity Medical Reseach, Waterloo, Ontario, Canada, and colleagues assessed the clinical effectiveness of ISA247**, a new type of calcineurin inhibitor intended for the treatment of autoimmune diseases such as psoriasis and uveitis, and prevention of organ transplant rejection. They did a placebo-controlled randomised trial of 451 patients aged 18-65 years with plaque psoriasis involving at least 10% of the body surface area. The patients were divided into four groups, all of whom received their treatment orally twice daily in dermatology clinics. The first (107 patients) received ISA247 at 0.2mg/kg body weight; the second (113) received ISA247 at 0.3mg/kg body weight; the third (116) received ISA247 at 0.4mg/kg, and the fourth group (115) received placebo. Treatment effectiveness was measured by whether it caused a 75% reduction in a measure called the psoriasis area and severity index score (PASI 75) at week 12. Patients were followed up for a total of 24 weeks.
The researchers found that, the higher the dose of ISA247, the better it performed. In the 0.4mg/kg group, 47% of patients achieved PASI 75; in the 0.3mg/kg group, this proportion was 25%; and in the 0.2mg/kg group, 16%. In the placebo group, only 4 of 115 patients (4%) achieved PASI 75.
The authors conclude: "ISA247 was safe and effective in the treatment of patients with moderate to severe psoriasis during 24 weeks, with the highest dose providing the best efficacy. The strong correlation between ISA247 concentrations and efficacy might allow for accurate dosing of patients compared with existing calcineurin inhibitors."
In an accompanying Comment, Dr Luigi Naldi, Unit of Dermatology and GISED Study Centre, Ospedali Riuniti di Bergamo, Italy, says: "New therapeutic options for the treatment of psoriasis create an increasing need for long-term observational studies and comparative trials in real life situations."
Notes to editors: *Calcineurin inhibitor: Calcineurin is involved in the production of a molecule called interleukin-2, which allows the activation and re-activation of T-cells involved in the molecular pathways that lead to psoriasis. Thus inhibiting calcineurin effectively "turns off" this signal which causes psoriasis.
**ISA247 was developed by Isotechnika, a biotech company in Edmonton, Alberta, Canada
Dr Kim Papp, Probity Medical Reseach, Waterloo, Ontario, Canada T) +1 519 579 9535 E) kapapp@probitymedical.com
Dr Luigi Naldi, Unit of Dermatology and GISED Study Centre, Ospedali Riuniti di Bergamo, Italy T) +39 035266458 / +39 3483363505 E) luigi.naldi@gised.it
PDF OF ARTICLE: http://multimedia.thelancet.com/pdf/press/psoriasis.pdf
Journal
The Lancet