- Design
- Open-label, assessor-blinded single-arm feasibility study with historic placebo comparison
- Population
- 20 adults with moderate to severe palmoplantar pustulosis at a UK specialist centre
- Primary outcome
- Feasibility: recruitment, adherence, acceptability; PP-PASI change secondary
- Effect
- PP-PASI 20.3 to 4.6 at 8 weeks; adjusted difference vs historic placebo −12.3 (95% CI −15.8 to −8.9)
Palmoplantar pustulosis is disabling, often resistant to treatment, and hard to trial. This UK open-label study at a national centre gave 20 adults with moderate to severe disease upadacitinib 30 mg daily for eight weeks (15 mg for higher-risk patients), with blinded assessment.
Mean PP-PASI fell from 20.3 to 4.6. Against historic placebo data from an earlier trial with matched procedures, the adjusted difference was 12.3 points in favour of upadacitinib (95% CI 8.9 to 15.8). All participants reached PP-PASI50 and 65% reached PP-PASI75. Headache, acne and upper respiratory infection were the commonest adverse events.
The main aim was feasibility, which was met. The efficacy figures come from 20 open-label patients compared with another trial's placebo group, which can flatter a drug.
This supports a proper randomised trial. JAK inhibitors carry boxed warnings on cardiovascular events, thrombosis and malignancy, particularly in older smokers, which is relevant because most people with this condition smoke.
- Upadacitinib is not licensed for palmoplantar pustulosis; this is exploratory evidence
- Ask about and support smoking cessation in every patient with palmoplantar pustulosis
- Weigh JAK inhibitor warnings on thrombosis, cardiovascular events and cancer, especially in smokers over 50
- Monitor for acne and infections if a JAK inhibitor is used off-label
Why it matters
It is one of few signals of a strong response in a condition with little that works.
Don't overread it
Twenty open-label patients against historic placebo cannot establish efficacy.
The statistics, in plain English
The 12.3-point difference compares this group with a placebo group from a different trial. That historic comparison is weaker than randomisation, because the two groups may differ in ways that were not measured.
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