Upadacitinib Feasible for Palmoplantar Pustulosis: David Gleeson, BM BCH, PhD

A single-center feasibility trial found that upadacitinib met all prespecified recruitment, adherence, and acceptability thresholds in patients with palmoplantar pustulosis (PPP), while also producing a markedly larger reduction in disease severity than a historic placebo comparator, according to David Gleeson, BM BCh, PhD, a dermatology registrar at St John's Institute of Dermatology and NIHR academic clinical fellow at King's College London. Gleeson discussed the late-breaking JAKPPPOT trial data, presented at the 2026 European Academy of Dermatology and Venereology (EADV) Congress held in Vienna, Austria, from September 30-October 3, in an interview with HCPLive.

PPP has no licensed therapies in the United Kingdom or Europe, and Gleeson said progress has been limited by the condition's rarity and its underlying biological complexity, which combines T-helper 17 activation seen in chronic plaque psoriasis with pathways more typical of eczema. Janus kinase (JAK) inhibitors, he said, are mechanistically attractive because they can suppress multiple inflammatory pathways simultaneously, but regulatory concerns about JAK-associated cardiovascular and malignancy risk made a feasibility trial necessary first, particularly given that most people with PPP currently or previously smoke.

Of 67 individuals approached, 28 (41.8%) consented and 20 (71.4%) started treatment with upadacitinib 30 mg once daily for 8 weeks (mean age 46.0 years; 85% female; 90% with a smoking history).¹ All 3 prespecified feasibility domains were met: adherence of at least 80% was achieved by 19 of 20 participants, and 18 of 19 rated the treatment acceptable or completely acceptable.¹ On efficacy, mean Palmoplantar Pustulosis Psoriasis Area and Severity Index (PP-PASI) fell from 20.3 to 4.6 at week 8 with upadacitinib, compared with 18.0 to 15.4 in a matched historic placebo cohort drawn from the APRICOT anakinra trial (baseline-adjusted difference, −12.3; 95% CI, −15.8 to −8.9), with PP-PASI75 achieved by 65.0% of upadacitinib-treated patients versus 3.2% with historic placebo.¹ ²

"There was an average of 77% reduction in disease severity in just 8 weeks of treatment, which is a bit of a… game changer in PPP," Gleeson said.

Gleeson noted that benefit did not persist once treatment stopped: after an 8-week treatment period, mean PP-PASI rose from 4.6 back to 12.2 by week 12, a 4-week washout later. He said this is consistent with JAK inhibitors acting quickly but clearing the system quickly as well, suggesting the drugs manage symptoms rather than altering the underlying disease process, and that interruptions in therapy, for illness or surgery, for example, would likely be followed by a return of symptoms. He also pointed to a screening finding relevant to future trial design: nearly 30% of potential participants approached were ineligible specifically due to cardiovascular or malignancy risk factors, underscoring both the need for individualized risk-benefit assessment across different JAK inhibitors and the recruitment challenges a larger trial would face.

Looking ahead, Gleeson said a definitive trial should be longer, larger, and ideally compare a JAK inhibitor against an active comparator, such as acitretin or a biologic like guselkumab, rather than placebo, both to generate richer comparative data and to reduce the burden on participants with a disease he described as highly debilitating.

Gleeson reported no relevant disclosures.

References

1. Gleeson D, Chapman S, Qin N, et al. JAKPPPOT: a feasibility trial assessing upadacitinib in palmoplantar pustulosis. Late-breaking abstract LB-155 presented at: European Academy of Dermatology and Venereology (EADV) Congress 2026; September 30-October 3, 2026; Vienna, Austria.

2. Cro S, Cornelius VR, Pink AE, et al; APRICOT Study Group. Anakinra for palmoplantar pustulosis: results from a randomized, double-blind, multicentre, two-staged, adaptive placebo-controlled trial (APRICOT). Br J Dermatol. 2022;186(2):245-256. doi:10.1111/bjd.20653