Guselkumab, an anti-interleukin 23 monoclonal antibody, may hold benefits for patients with moderate to severe palmoplantar pustulosis (PPP), according to the results of phase 2, double-blind, randomized, placebo-controlled, 24-week trial (ClinicalTrials.gov identifier: NCT01845987) conducted at 11 centers in Japan and published in JAMA Dermatology.
The aim of the current study, which was conducted between May 14, 2013, and September 27, 2014, was to evaluate the efficacy and safety of guselkumab in patients with moderate to severe PPP that did not respond adequately to conventional therapies.
This parallel-group study included a screening period (6 weeks) and a double-blind period (24 weeks). A total of 49 patients were randomly assigned in a 1:1 ratio to receive guselkumab 200 mg (n=25) administered by subcutaneous injection or matching placebo (n=24) at weeks 0 and 4.
The primary efficacy endpoint was change from baseline in the palmoplantar pustulosis severity index score at week 16. The palmoplantar pustulosis severity index score measures the severity of PPP lesions on patients’ palms and soles, with their response to therapy rated on a scale of 0 to 12. During screening, the most severely affected areas on the palms and soles were identified and were evaluated for erythema, pustules or vesicles, and desquamation or scale at each visit.
Overall, 71% of the participants were women, and the median patient age was 52 years (range, 28-77 years). Of the 49 randomized patients, 41 completed the study at week 24.
At week 16, mean palmoplantar pustulosis severity index total scores improved significantly from baseline in the guselkumab group (−3.3 [standard deviation, 2.43]) vs the placebo group (−1.8 [standard deviation, 2.09]; least squares mean difference, −1.5; 95% CI, −2.9 to −0.2; P =.03.) Also at week 16, PPP area and severity index scores (least squares mean difference, −5.65; 95% CI, −9.80 to −1.50; P =.009) and proportion of participants attaining 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P =.009) improved significantly.
A higher proportion of patients in the guselkumab group vs the placebo group had a physician’s global assessment score of ≤1. Among guselkumab-treated patients, improvement in efficacy scores was maintained through week 24. Moreover, significant reductions from baseline in serum interleukin 17A and interleukin 17F cytokine levels were observed at weeks 4 and 16 in the guselkumab group.
The frequency of adverse events was comparable between the 2 groups. The most common adverse events included nasopharyngitis, headache, contact dermatitis, and injection-site erythema.
The investigators concluded that longer-term phase 3 studies with a placebo crossover design and continued maintenance dosing in larger patient populations are warranted to further characterize the therapeutic benefits of guselkumab for the treatment of PPP.
Terui T, Kobayashi S, Okubo Y, Murakami M, Hirose K, Kubo H. Efficacy and safety of guselkumab, an anti-interleukin 23 monoclonal antibody, for palmoplantar pustulosis: a randomized clinical trial [published online February 7, 2018]. JAMA Dermatol. doi: 10.1001/jamadermatol.2017.5937