In a phase III trial, a new treatment for moderate to severe plaque psoriasis has been proven safe and effective. Additionally, there is almost a linear relationship between drug dose and response, which suggests that patients can be accurately dosed in order to achieve a clinical response while minimizing side effects. These results were published on April 18, 2008 in The Lancet.
The most effective treatment for psoriasis presently is the calcineurin inhibitor ciclosporin. However, use of this drug has a toxic effect on the kidneys, which restricts its long-term use. Newer treatments, such as infliximab, are safe and effective for plaque psoriasis treatment, but their high costs, inconvenient administration methods, and general lack of safety and effectiveness data restrict their widespread use.
This new treatment, ISA247, is a new type of calcineurin inhibitor intended to treat autoimmune diseases such as psoriasis, uveitis, and organ transplant rejection. To investigate this new treatment, Dr Kim Papp, Probity Medical Reseach, Waterloo, Ontario, Canada, conducted a placebo-controlled randomized trial on 451 patients aged 18-65 years with plaque psoriasis involving at least 10% of body surface area.
The patients were divided into four groups, each of which receieved treatment orally twice daily at dermatology clinics. The groups were dosed the following amounts of ISA247: the first, with 107 patients, received 0.2 mg/kg body weight; the second, with 113 patients, receieved 0.3 mg/kg body weight; the third, with 116 patients, receieved 0.4 mg/kg body weight; the fourth, with 115 patients, received a placebo. Patients were followed up for a total of 24 weeks.
Effectiveness of treatment was measured by whether a 75% reduction in psoriasis area and severity index score (PASI 75) at week 12. It was found that when the ISA247 dose was higher, it performed better. That is, in the 0.4 mg/kg group, 47% of patients achieved PASI75, in the 0.3 mg/kg group it was 25%, in the 0.2 mg/kg group it was 16%, and in the placebo 4%.
The authors conclude with positive comments about the potential of this new drug. “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.”
Dr Luigi Naldi, of the Unit of Dermatology and GISED Study Centre, Ospedali Riuniti di Bergamo, Italy, contributed a comment in which he notes the future implications of these results on psoriasis research. “New therapeutic options for the treatment of psoriasis create an increasing need for long-term observational studies and comparative trials in real life situations.”
Efficacy of ISA247 in plaque psoriasis: a randomised, multicentre, double-blind, placebo-controlled phase III study
K Papp, R Bissonnette, L Rosoph, N Wasel, C W Lynde, G Searles, N H Shear, R B Huizinga, W P Maksymowych
Lancet 2008; 371: 1337-42
Written by Anna Sophia McKenney