Efficacy and Safety of Guselkumab, an Anti-interleukin 23 Monoclonal Antibody, for Palmoplantar Pustulosis: A Randomized Clinical Trial

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.

Trial registration: clinicaltrials.gov Identifier: NCT01845987.

Conflict of interest statement

Conflict of Interest Disclosures: Drs Kubo and Hirose are employees of Janssen Pharmaceutical K.K., Tokyo, Japan. Drs Terui, Murakami, Okubo, and Kobayashi have received research support and performed consulting work for Janssen Pharmaceutical K.K. No other disclosures were reported.

Figures

Figure 1.. Study Design Flow Diagram

A total of 49 patients were randomly assigned (1:1) to receive 200 mg of guselkumab (two 1-mL subcutaneous injections) or placebo at week 0 and week 4. After randomization (week 0), patients returned to the study site for 9 evaluation visits during the 24-week double-blind period. aNone had a disease flare on drug withdrawal. bReceived guselkumab or placebo only at week 0 and discontinued.

Figure 2.. Efficacy Outcomes Through Week 24 (Full Analysis Set)

A, Mean change from baseline in palmoplantar pustulosis severity index (PPSI) total score through week 24 (last observation carried forward, full analysis set); guselkumab, n = 25; placebo, n = 24. B, Mean change from baseline in palmoplantar pustulosis area and severity index (PPPASI) total score through week 24 (last observation carried forward, full analysis set). Error bars indicate standard deviation. A and B, P values shown are for the least squares mean difference (guselkumab vs placebo) at week 16. C, Percentage of patients achieving proportion of patients with 50% or greater improvement from baseline of PPPASI total score (PPPASI-50) response through week 24 (nonresponder imputation, full analysis set). D, Percentage of patients with physician’s global assessment scores of 1 or less through week 24 (nonresponder imputation, full analysis set).