The British journal of dermatology · 2026
Upadacitinib for Palmoplantar Pustulosis: An Open-label, Assessor-blinded Feasibility Study Using Historic Control Data (JAKPPPOT).
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Gleeson David, Chapman Sarah, Qin Neville, Gregory John, Mitchell-Gears Amelia, Pizzato Jade, Powell Kingsley, Sagoo Manpreet K, Ye Weiyu, Moorhead Lucy, Barker Jonathan, Galloway James, McAteer Helen, Woolf Richard, Pink Andrew E, Cro Suzie, Mahil Satveer, Smith Catherine
Аннотация
BACKGROUND: Palmoplantar pustulosis (PPP) is a rare, disabling inflammatory skin disease with substantial unmet need. Janus kinase inhibitors (JAKi) target inflammatory pathways implicated in PPP. High smoking prevalence and rare disease status mean that a randomised controlled trial (RCT) to evaluate the efficacy and safety of JAKi in PPP may be challenging.
OBJECTIVES: To determine the feasibility of a future RCT of JAKi therapy in PPP and generate an exploratory estimate of treatment effect.
METHODS: This open-label, assessor-blinded feasibility trial, conducted at a UK national specialist dermatology centre, enrolled adults (≥18 years) with moderate-to-severe PPP and treated them with upadacitinib 30 mg once daily for 8 weeks (15 mg for higher-risk individuals). Primary feasibility endpoints were recruitment (consent rate), adherence (≥80% of days covered), and acceptability ('completely acceptable'/'acceptable' on post-treatment 5-point Likert scale). Secondary outcomes included change from baseline in Palmoplantar Pustulosis-Psoriasis Area and Severity Index (PP-PASI) and safety. Study procedures were harmonised with a previous RCT in PPP, permitting comparison with historic placebo data. Analyses were descriptive with baseline-adjusted PP-PASI change estimated with a linear (Gaussian) mixed-effects model.
RESULTS: All prespecified feasibility criteria were met. Of 67 contacted individuals, 28 consented (41.8%), and 20 started treatment (71.4%; mean age 46.0 years; 85% female). Adherence ≥80% was achieved by 19/20 participants (95%), with a mean proportion of days covered of 95.7% (SD 9.7). 18/19 participants (94.7%) viewed treatment as acceptable. Mean PP-PASI decreased from 20.3 (SD 10.6) at baseline to 4.6 (SD 4.5) at week 8 with upadacitinib, versus 18.0 (SD 10.4) to 15.4 (SD 10.1) with historic placebo. Baseline-adjusted PP-PASI change at week 8 for upadacitinib relative to historic placebo was -12.3 (95% CI -15.8 to -8.9) in favour of upadacitinib. PP-PASI50 and PP-PASI75 responses with upadacitinib relative to historic placebo were 100% vs 16.1% and 65.0% vs 3.2%. The most common adverse events were headache, acne, and upper respiratory tract infections.
CONCLUSIONS: This study demonstrates that a definitive trial of JAK inhibition in PPP is feasible and identifies an encouraging exploratory efficacy signal. The findings support progression to a multicentre active-comparator randomised controlled trial.
OBJECTIVES: To determine the feasibility of a future RCT of JAKi therapy in PPP and generate an exploratory estimate of treatment effect.
METHODS: This open-label, assessor-blinded feasibility trial, conducted at a UK national specialist dermatology centre, enrolled adults (≥18 years) with moderate-to-severe PPP and treated them with upadacitinib 30 mg once daily for 8 weeks (15 mg for higher-risk individuals). Primary feasibility endpoints were recruitment (consent rate), adherence (≥80% of days covered), and acceptability ('completely acceptable'/'acceptable' on post-treatment 5-point Likert scale). Secondary outcomes included change from baseline in Palmoplantar Pustulosis-Psoriasis Area and Severity Index (PP-PASI) and safety. Study procedures were harmonised with a previous RCT in PPP, permitting comparison with historic placebo data. Analyses were descriptive with baseline-adjusted PP-PASI change estimated with a linear (Gaussian) mixed-effects model.
RESULTS: All prespecified feasibility criteria were met. Of 67 contacted individuals, 28 consented (41.8%), and 20 started treatment (71.4%; mean age 46.0 years; 85% female). Adherence ≥80% was achieved by 19/20 participants (95%), with a mean proportion of days covered of 95.7% (SD 9.7). 18/19 participants (94.7%) viewed treatment as acceptable. Mean PP-PASI decreased from 20.3 (SD 10.6) at baseline to 4.6 (SD 4.5) at week 8 with upadacitinib, versus 18.0 (SD 10.4) to 15.4 (SD 10.1) with historic placebo. Baseline-adjusted PP-PASI change at week 8 for upadacitinib relative to historic placebo was -12.3 (95% CI -15.8 to -8.9) in favour of upadacitinib. PP-PASI50 and PP-PASI75 responses with upadacitinib relative to historic placebo were 100% vs 16.1% and 65.0% vs 3.2%. The most common adverse events were headache, acne, and upper respiratory tract infections.
CONCLUSIONS: This study demonstrates that a definitive trial of JAK inhibition in PPP is feasible and identifies an encouraging exploratory efficacy signal. The findings support progression to a multicentre active-comparator randomised controlled trial.