Upadacitinib showed a large early signal in palmoplantar pustulosis in a small open-label study

Design

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

Population

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

Primary outcome

Feasibility (recruitment, adherence, acceptability); PP-PASI change at week 8

Effect

PP-PASI 20.3 → 4.6; adjusted difference vs historic placebo −12.3 (−15.8 to −8.9); PP-PASI75 65% vs 3.2%

Palmoplantar pustulosis is disabling and responds poorly to most systemic treatments. This UK single-centre feasibility study treated 20 adults with moderate-to-severe disease with upadacitinib 30 mg daily (15 mg in higher-risk patients) for eight weeks, and compared them with placebo data from an earlier trial run to the same procedures.

The feasibility targets were met: 95% adherence and 94.7% acceptability. Mean PP-PASI fell from 20.3 to 4.6, against 18.0 to 15.4 in the historic placebo group — an adjusted difference of −12.3 (95% CI −15.8 to −8.9). All treated patients reached PP-PASI50 and 65% PP-PASI75, against 16.1% and 3.2% with historic placebo. Headache, acne and upper respiratory infections were the most common adverse events.

This is not yet evidence to prescribe. The design cannot exclude regression to the mean or a placebo response in an unblinded study. It justifies the randomised trial the authors are planning, and it tells clinicians which class to watch.

• Do not start a JAK inhibitor for palmoplantar pustulosis on this evidence outside a trial or specialist decision.
• Ask every patient with palmoplantar pustulosis about smoking; most smoke, and stopping helps.
• Screen for tuberculosis, hepatitis B and cardiovascular risk before any JAK inhibitor.
• Refer refractory palmoplantar pustulosis to a specialist centre rather than escalating empirically.

Why it matters

A disease with few effective treatments now has a plausible candidate worth a definitive trial.

Don't overread it

Twenty patients, no concurrent control and no blinding of treatment; the effect size is exploratory.

The statistics, in plain English

The comparison group is historic placebo data from a different trial, not patients randomised at the same time. Differences in who was recruited, and knowing you are on an active drug, can both inflate apparent benefit.

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