Upadacitinib in palmoplantar pustulosis: a strong early signal from 20 patients

Design

Open-label, assessor-blinded feasibility study with historic placebo comparison

Population

20 adults with moderate-to-severe palmoplantar pustulosis, one UK centre

Primary outcome

Feasibility (recruitment, adherence, acceptability); PP-PASI change secondary

Effect

PP-PASI 20.3 → 4.6 at 8 weeks; adjusted difference vs historic placebo −12.3 (−15.8 to −8.9)

Palmoplantar pustulosis is hard to treat and biologics that work in plaque psoriasis have often disappointed. A UK specialist centre ran an open-label feasibility study of upadacitinib, a JAK inhibitor, at 30 mg daily for eight weeks (15 mg for higher-risk patients) in 20 adults with moderate-to-severe disease. Assessors were blinded, and the results were set against placebo data from an earlier trial run with matching methods.

Recruitment, adherence and acceptability targets were all met. The palmoplantar severity score fell from about 20 to under 5. Every patient achieved at least a 50% improvement, and 65% achieved 75%, against 16% and 3% in the historic placebo group. Headache, acne and upper respiratory infection were the commonest side effects.

This is a feasibility study with a historical comparison, not a randomised trial, and eight weeks says nothing about durability or long-term safety. JAK inhibitors carry boxed warnings on cardiovascular events, malignancy, thrombosis and serious infection, which matter in a population with high smoking rates. The authors are planning a multicentre trial against an active comparator.

• Recognise that JAK inhibition is a promising but unproven option for palmoplantar pustulosis; randomised data are still awaited.
• Ask about and support smoking cessation in every patient with palmoplantar pustulosis — smoking is strongly linked to the disease.
• Screen for cardiovascular risk, thrombosis history, infection and malignancy before any JAK inhibitor use.
• Consider referral to a specialist centre or trial for patients who have failed conventional treatment.

Why it matters

A disease with few effective options now has a candidate drug with a large enough signal to justify a definitive trial.

Don't overread it

Open-label treatment compared with historic placebo data can exaggerate benefit; this is not evidence of efficacy on its own.

The statistics, in plain English

The adjusted difference of −12.3 points against historic placebo (95% CI −15.8 to −8.9) is large, but historic controls were treated at a different time and may differ in ways the adjustment cannot capture.

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