Encouraging findings add support to a definitive randomized controlled trial of JAKi therapy in palmoplantar pustulosis, and provide an early indication of treatment effect.
Palmoplantar pustulosis (PPP) is a rare, chronic inflammatory skin disease characterized by painful pustules on the palms of the hands and soles of the feet. The condition can make everyday activities extremely difficult, yet treatment options remain limited with no therapies currently licensed in the UK or Europe.
At the EADV Congress 2026, new data exploring the potential of Janus kinase inhibitors (JAKi) for PPP were presented during the late-breaking session on Thursday, 1 October.
We spoke with study investigator Dr David Gleeson (Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, UK) about JAKPPPOT, a feasibility trial assessing whether a definitive randomized controlled trial of JAKi therapy in PPP could be conducted. The study also generated an exploratory estimate of treatment effect to inform future sample size calculations. We discussed its findings and what they could mean for future research into this class of medication for PPP.
What were the key aims of the JAKPPPOT trial?
PPP is a variant of psoriasis and an incredibly debilitating condition. Unfortunately, we currently have no really effective treatments, so many people living with PPP continue to suffer.
JAK inhibitors are a relatively new class of medication. We use them in other dermatological conditions, and they may also have potential in PPP. However, their risk profile needs careful consideration.
JAKi have been associated with potential risks of cardiovascular disease and malignancy. This is particularly relevant because roughly 80% of people with PPP have a history of smoking, so the risks linked to these drugs may overlap with those of the patient population.
We therefore wanted to run a feasibility trial before moving to a large, definitive RCT. We focused on three questions. Could we recruit enough patients? Would participants take the treatment as prescribed? And, fundamentally, would the treatment be acceptable to people living with PPP? Even if it might work, would patients consider the potential risks acceptable? We also looked at whether the drug showed evidence of efficacy and how large that effect might be.
How was the JAKPPPOT trial conducted?
JAKPPPOT used an innovative trial design called a historic placebo-matched control trial. To do this, we took placebo data from 31 patients with PPP who received placebo in a previous PPP trial and used that as a comparison population. We then carefully matched our trial protocol and all the processes to those of the previous trial so that we could use it as a mirror group.
What did JAKPPPOT suggest about the feasibility of an RCT of JAKi in PPP and beyond?
What was observed in terms of the safety of JAKi in PPP?
It is important to always think about safety whenever you are conducting a trial like this. Crucially, no new worrying safety signals were detected, which is really reassuring.
We had one patient stop the trial early because of weight gain, which is a recognized side effect of JAK inhibitors. One patient stopped early due to an eye problem, but this was thought to be related to a longstanding patient risk factor. Known side effects of JAK inhibitors were also noted but overall, the findings were very much in keeping with the expected safety profile and were quite reassuring.
What do these findings suggest about the potential of JAK inhibitors in PPP?
By presenting these findings, we hope to put a marker in the sand and raise awareness of the potential of JAKi for people living with PPP.
These results suggest that these drugs may target relevant disease pathways and warrant further investigation. However, a definitive trial is needed. Whether that is publicly funded, carried out in partnership with industry or led entirely by industry, we’d be happy to work with anyone interested in taking this forward.
Ultimately, it’s about keeping that momentum going and building the evidence needed to improve treatment options for patients.
More about JAKPPPOT
JAKPPPOT enrolled adults aged 18 years or older with dermatologist-confirmed moderate-to-severe PPP. Participants received the JAKi upadacitinib once daily for 8 weeks. The dose was 30 mg, or 15 mg for higher-risk individuals in line with Medicines and Healthcare products Regulatory Agency (MHRA) guidance.
The study assessed whether a larger, definitive trial would be feasible by examining recruitment, adherence and acceptability. Recruitment was measured as the proportion of eligible patients who consented to take part. Adherence assessed whether participants took treatment on at least 80% of days, while acceptability was rated by participants on a five-point scale, from “completely unacceptable” to “completely acceptable”.
Prespecified green, amber and red progression criteria guided decisions about a definitive trial. The thresholds supporting progression were at least 40% for recruitment, 80% for adherence and 80% for acceptability.
Secondary outcomes included disease severity, assessed using the Palmoplantar Pustulosis Area and Severity Index (PP-PASI) and the PPP Investigator Global Assessment (PPP-IGA). Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was also assessed.
Historical placebo data came from APRICOT, a closely matched UK multicentre randomised controlled trial (RCT) of anakinra, an interleukin-1 antagonist, in PPP.
Sources:
This information was presented at the EADV Congress 2026, Vienna, 30 September–3 October 2026. More information about the meeting is available here.
Related abstract: Gleeson D, Chapman S, Qin N, et al. JAKPPPOT: a feasibility trial assessing upadacitinib in palmoplantar pustulosis. Abstract no. 155. Presented at: EADV Congress 2026; 1 October 2026; Vienna, Austria.
Cite: JAKPPPOT investigates the feasibility of a definitive JAKi trial in PPP. touchDERMATOLOGY. 12 October, 2026.
Disclosure: No funding was received for the publication of this content. Thank you to Dr Gleeson for sharing his expert insights. Dr Gleeson discloses grant/research support from the National Institute for Health and Care Research (NIHR) and previous educational support from Eli Lilly.
Editor: Gina Furnival, Head of Content
touchDERMATOLOGY coverage of EADV 2026: This content has been developed independently by Touch Medical Media for touchDERMATOLOGY. touchDERMATOLOGY was an official media partner of the EADV Congress 2026. touchDERMATOLOGY is not affiliated with the EADV. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
