Secukinumab not superior to placebo for moderate-to-severe palmoplantar pustular psoriasis
Treatment with 300-mg secukinumab confers benefits among patients with palmoplantar pustular psoriasis (PPP) in terms of Palmoplantar Psoriasis Area and Severity Index (PPPASI75) responses over 52 weeks and improved quality of life (QOL), results of the 2PRECISE study have shown.
2PRECISE was a phase IIIb multicentre, randomized, double-blind, placebo-controlled, parallel-group trial that compared treatment with 300-mg secukinumab (n=79), 150-mg secukinumab (n=80) and placebo (n=78) in patients with moderate-to-severe PPP over 52 weeks.
The primary endpoint was to demonstrate the superiority of secukinumab 300 mg and/or 150 mg to placebo in these patients at week 16, as measured by difference in the rate of achievement of a 75-percent improvement from baseline in PPPASI75.
Secukinumab did not show superiority to placebo. Only 26.6 percent of patients treated with 300-mg secukinumab achieved PPPASI75 compared with 14.1 percent of those who received placebo at week 16 (odds ratio, 2.62; 95 percent CI, 1.04–6.60; p=0.0411). At week 52, 41.8 percent of patients in the 300-mg secukinumab group achieved PPPASI75. [J Am Acad Dermatol 2019;80:1344-1352]
Responses of 0 or 1 in Dermatology Life Quality Index (DLQI) occurred more frequently among patients treated with 300-mg secukinumab vs placebo (13.0 percent vs 4.3 percent) at week 16. Of the patients in the 300-mg secukinumab group, 43.1 percent achieved a DLQI response of 0 or 1 at week 52. Furthermore, there were no unexpected adverse events reported.
“The primary endpoint of secukinumab superiority to placebo at week 16 in patients with PPP was not met in 2PRECISE,” researchers said. “However, the reduction of PPPASI by 75 percent in more than 41 percent of patients and the achievement of a DLQI of 0 or 1 in 43 percent of patients treated with secukinumab 300 mg over 52 weeks … represents potential benefit in a difficult-to-treat condition.”
Researchers also claimed that, so far, efficacy similar to that seen at 52 weeks had not been reported in this patient population for any other PPP treatment. [Int J Dermatol 2014;53:e464-e466; Cochrane Database Syst Rev 2006;CD001433]
The importance of long-term disease control is highlighted in published guidance on the treatment of PPP. For that reason, the efficacy of secukinumab after 52 weeks may represent a more meaningful timepoint, according to researchers. [Br J Dermatol 2011;164:942-946]
The small difference between secukinumab and placebo at week 16 might have resulted from variation in the natural course of PPP, which remains unclear, said researchers, adding that the week 52 response to 300-mg secukinumab is clinically relevant in this treatment-refractory condition.
A significant improvement in health-related QOL, especially in the context of the mean baseline DLQI of 16 to 17, supports the said finding. [J Invest Dermatol 2005;125:659-664]
This study was limited by its small sample size and characteristics of the PPP disease course, according to the researchers.
PPP is a chronic debilitating condition, but the need for long-term therapeutic options remains unmet.