Risankizumab in Japanese patients with moderate-to-severe palmoplantar pustulosis: Results from the randomized, phase 3 JumPPP study
Risankizumab in Japanese patients with moderate-to-severe palmoplantar pustulosis: Results from the randomized, phase 3 JumPPP study
Okubo Y, Murakami M, Kobayashi S, et al. J Dermatol. 2025 Apr;52(4):593-602. doi:10.1111/1346-8138.17659.
Introduction
Palmoplantar pustulosis (PPP) is a chronic, debilitating inflammatory skin disorder characterized by sterile pustules localized on the palms and soles, often significantly impairing quality of life. Therapeutic options have historically been limited, with many patients experiencing refractory disease. The JumPPP study addresses this unmet need by evaluating risankizumab, an interleukin-23 p19 inhibitor, targeting a key inflammatory pathway implicated in PPP pathogenesis.
This randomized, phase 3 trial specifically enrolled Japanese adults with moderate-to-severe PPP, aiming to establish the efficacy and safety profile of risankizumab in this population and provide evidence for a novel targeted treatment approach.
Study Overview
Study Type: Randomized, phase 3, multicenter, placebo-controlled, double-blind trial (NCT04451720)
Population: 119 Japanese adults with moderate-to-severe palmoplantar pustulosis
Intervention: Risankizumab 150 mg or placebo administered at weeks 0 and 4, followed by open-label risankizumab to week 52 (initial RZB group) or week 56 (initial placebo group)
Outcomes: Primary endpoint was change in Palmoplantar Pustulosis Area and Severity Index (PPPASI) at week 16; secondary endpoints included PPPASI 50 and PPPASI 75 response rates; safety assessed through week 76
The study design incorporated an initial double-blind phase followed by an open-label extension, allowing assessment of both short-term efficacy and long-term durability and safety of risankizumab treatment.
Key Findings
- Significant improvement in PPPASI score at week 16 with risankizumab vs placebo (least squares mean difference: -3.48; p < 0.05)
- Higher proportion achieving PPPASI 50 at week 16 in risankizumab group (41.0%) compared to placebo (24.1%), nominal p < 0.05
- No significant difference in PPPASI 75 response at week 16 between risankizumab (13.1%) and placebo (15.5%), nominal p = 0.74
- Improvements with risankizumab generally sustained through week 68
- Safety profile consistent with prior risankizumab studies in psoriasis; no unexpected safety signals reported
Evidence Synthesis
The JumPPP study’s positive findings align with a growing body of evidence supporting IL-23 pathway inhibition as an effective therapeutic strategy for PPP in Japanese patients.
Supporting Clinical Trials and Reviews
- Terui et al., 2019: A pivotal phase 3 randomized trial demonstrated that guselkumab, another IL-23 inhibitor, significantly improved PPPASI scores versus placebo, establishing the efficacy of this drug class in PPP (PMID: 31268476).
- Okubo et al., 2021: Long-term extension study confirmed sustained efficacy and favorable safety of guselkumab through 1.5 years, highlighting durability of IL-23 inhibition in PPP management (PMID: 34453358).
- Fukasawa et al., 2024: A systematic review and network meta-analysis of seven randomized controlled trials identified guselkumab as having the highest probability of achieving desired PPPASI outcomes, reinforcing the IL-23 inhibitor class as a leading treatment option (PMID: 37684049).
Summary Table: Key Related Studies on IL-23 Inhibitors in PPP
| Study | Design & Population | Intervention | Key Outcomes | Reference |
|---|---|---|---|---|
| JumPPP (Okubo et al., 2025) | Phase 3 RCT; 119 Japanese adults with moderate-to-severe PPP | Risankizumab 150 mg vs placebo | Significant PPPASI improvement at week 16; sustained efficacy to week 68; favorable safety | PMID: 36484049 |
| Terui et al., 2019 | Phase 3 RCT; Japanese PPP patients | Guselkumab vs placebo | Significant PPPASI improvement; established IL-23 inhibition efficacy | PMID: 31268476 |
| Okubo et al., 2021 | Extension study; 1.5 years follow-up | Guselkumab | Sustained efficacy and safety over long term | PMID: 34453358 |
| Fukasawa et al., 2024 | Systematic review and network meta-analysis of 7 RCTs | Various PPP treatments including IL-23 inhibitors | Guselkumab highest probability for PPPASI response; supports IL-23 class | PMID: 37684049 |
While risankizumab’s efficacy in PPP is now supported by this robust phase 3 trial, direct head-to-head comparisons with other IL-23 inhibitors such as guselkumab remain an important evidence gap. Additionally, integration of risankizumab data into future meta-analyses will further clarify its relative position within the PPP treatment landscape.
Clinical Implications
- Risankizumab offers a well-tolerated, effective targeted therapy for moderate-to-severe PPP in Japanese patients, expanding treatment options beyond conventional therapies.
- The sustained PPPASI improvements through 68 weeks support risankizumab as a viable long-term management strategy for this chronic condition.
- Clinicians should consider IL-23 pathway inhibition as a preferred therapeutic class for PPP, with risankizumab representing a valuable addition to the biologic armamentarium.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Robust randomized, double-blind, placebo-controlled phase 3 design | Relatively small sample size (119 patients) limits generalizability |
| Long-term follow-up (up to 68 weeks efficacy, 76 weeks safety) | No direct head-to-head comparison with other IL-23 inhibitors like guselkumab |
| Comprehensive safety assessment consistent with prior risankizumab data | Study population limited to Japanese adults; applicability to other ethnicities uncertain |
| Use of validated PPPASI outcome measures | Nominal p-values for some secondary endpoints; potential for type I error |
Future Directions
Future research should focus on direct comparative trials between risankizumab and other IL-23 inhibitors, particularly guselkumab, to delineate relative efficacy and safety profiles in PPP. Additionally, inclusion of risankizumab data in comprehensive meta-analyses will enhance evidence synthesis and guide optimal treatment selection.
Exploration of risankizumab’s effectiveness in diverse ethnic populations and real-world settings will further inform its clinical utility.
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References
- Terui T, Kobayashi S, Okubo Y, et al. Efficacy and Safety of Guselkumab in Japanese Patients With Palmoplantar Pustulosis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2019 Oct 1;155(10):1153-1161. doi: 10.1001/jamadermatol.2019.1394. PMID: 31268476.
- Okubo Y, Morishima H, Zheng R, Terui T. Sustained efficacy and safety of guselkumab in patients with palmoplantar pustulosis through 1.5 years in a randomized phase 3 study. J Dermatol. 2021 Dec;48(12):1838-1853. doi: 10.1111/1346-8138.16132. PMID: 34453358.
- Fukasawa T, Yamashita T, Enomoto A, et al. Optimal treatments and outcome measures of palmoplantar pustulosis: A systematic review and network meta-analysis-based comparison of treatment efficacy. J Eur Acad Dermatol Venereol. 2024 Feb;38(2):281-288. doi: 10.1111/jdv.19499. PMID: 37684049.
