Efficacy and Safety of Guselkumab, an Anti–interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis

Abstract

IMPORTANCE Palmoplantar pustulosis (PPP) is a recalcitrant skin disease with no biologics currently approved for treatment. The involvement of interleukin 23 (IL-23) and cytokines of the type 17 helper T cell lineage in the pathogenesis of PPP has been recently postulated. OBJECTIVE To evaluate the efficacy and safety of guselkumab, an anti-IL-23 monoclonal antibody, in Japanese patients with PPP. DESIGN, SETTING, AND PARTICIPANTS This double-blind, randomized, placebo-controlled, parallel-group, 24-week trial was conducted between May 14, 2013, and September 27, 2014, at 11 centers in Japan. Participants were patients with moderate to severe PPP that did not respond adequately to conventional treatments. INTERVENTIONS Patients were randomized 1:1 to receive guselkumab, 200 mg, by subcutaneous injection or matching placebo at weeks 0 and 4. MAIN OUTCOMES AND MEASURES Changes in total scores of skin-related outcomes from baseline at the end of week 16 (primary clinical cutoff) and through week 24 were measured. Serum biomarker analyses were performed at baseline, week 4, and week 16, and safety was monitored through week 24. RESULTS Of 49 randomized patients (35 [71%] women; median [range] age, 52 [28-77] years), 41 completed the study at week 24. Mean (SD) PPP severity index total scores (primary end point) improved significantly from baseline in guselkumab-treated patients (−3.3 [2.43]) vs placebo (−1.8 [2.09]) (least squares mean difference, −1.5; 95% CI,-2.9 to-0.2; P = .03). 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 patients achieving 50% reduction in these scores (difference in proportion, 39.2; 95% CI, 14.0-64.3; P = .009) improved significantly. A numerically higher proportion of patients had a physician's global assessment score of 1 or less in the guselkumab group vs placebo. Improvement in efficacy scores was maintained through week 24 in the guselkumab group. Significant reductions from baseline in serum IL-17A and IL-17F cytokine levels were observed at weeks 4 and 16. Frequency of treatment-emergent adverse events was comparable between the guselkumab group (19 of 25 patients [76%]) and the placebo group (18 of 24 patients [75%]). Frequent adverse effects included nasopharyngitis (14 patients [29%]), headache (3 patients [6%]), contact dermatitis (3 patients [6%]), and injection site erythema (3 patients [6%]). No major safety concerns emerged during the study. CONCLUSIONS AND RELEVANCE Targeting IL-23 and its associated immune cascade with guselkumab may be a safe and useful therapeutic option for treatment of PPP.

Guselkumab, a human interleukin‐23 monoclonal antibody in Japanese patients with generalized pustular psoriasis and erythrodermic psoriasis: Efficacy and safety analyses of a 52‐week, phase 3, multicenter, open‐label study

“…There were no deaths, injection‐site reactions, anti‐guselkumab antibodies or serious infections reported in the study. The overall safety results of this study in Japanese patients treated with guselkumab were consistent with the previous studies conducted in a global population with moderate to severe plaque psoriasis and in Japanese patients with moderate to severe psoriasis and palmoplantar pustulosis …”

Nummular dermatitis on guselkumab for palmoplantar psoriasis

“…In a recent study of 49 patients conducted by Terui et al in 2018, guselkumab was used to treat palmoplantar pustulosis. Onset of clinical response within 2 weeks of therapy with a trend toward improvement until week 24 (Terui et al, ).…”

“…By antagonizing IL-23p19, this inflammatory pathway is disrupted and therefore is a viable biological therapy for these immune-mediated skin conditions. In a recent study of 49 patients conducted by Terui et al in 2018, guselkumab was used to treat palmoplantar pustulosis. Onset of clinical response within 2 weeks of therapy with a trend toward improvement until week 24 (Terui et al, 2018).…”

Pathogenic role of palatine tonsils in palmoplantar pustulosis: A review

“…In PPP skin lesions, the CCL20–CCR6 axis may contribute to a positive feedback loop involving the recruitment and migration of effector Th17 cells, as well as the amplification of inflammation and tissue destruction. This speculation was supported by the favorable outcome in a clinical trial using secukinumab (anti‐IL‐17A antibody) or guselkumab (anti‐IL‐23 antibody) for PPP patients; however, the limited efficacy showed that other factors were also involved in PPP pathogenesis …”