TOPLINE 

JAK inhibitor treatment using upadacitinib (Rinvoq) demonstrated feasibility in patients with palmoplantar pustulosis (PPP) and a signal that disease severity could be reduced vs placebo.

METHODOLOGY 

• The open-label JAKPPPOT study was a mixed-methods feasibility trial conducted at a specialist dermatology center in the UK to test whether JAK inhibition is possible in PPP.
• Sixty-seven adults (≥ 18 years of age) with moderate-to-severe PPP were invited to be treated with upadacitinib 30 mg once daily for 8 weeks. The dose was reduced to 15 mg if stipulated by the product’s prescribing information.  
• For comparison, the researchers used data from patients who had received placebo in the earlier APRICOT trial. JAKPPPOT followed the same procedures, visit schedule, and outcome measures as APRICOT so that the results from the two groups could be compared.
• Exploratory efficacy assessments included calculating the mean Palmoplantar Pustulosis Psoriasis Area and Severity Index (PP-PASI) score and mean change in PP-PASI scores at weeks 1, 4, 8, and 12.
• Feasibility criteria included achieving at least a 40% enrollment level, 80% or higher adherence to treatment, and at least 80% of patients finding JAK inhibitor treatment “acceptable.” 

TAKEAWAY 

• Most (60%) of the 20 participants who met the study’s inclusion criteria and gave their informed consent received the 30-mg once-daily dose of upadacitinib.
• The study population was 85% women, which was comparable to the historical placebo cohort. However, the study population in JAKPPPOT was younger than that in APRICOT (mean age, 46 vs 52 years, respectively), and baseline disease severity was worse (mean PP-PASI score, 20.3 vs 18.0).
• All prespecified feasibility criteria were met in 41.8% of participants enrolled in the study, 95% adhered to treatment, and 94.7% deemed the treatment to be acceptable.
• Mean PP-PASI scores decreased from 20.3 at baseline to 4.6 at week 8 with
• upadacitinib, vs 18.0 to 15.4 with the historic placebo. The baseline-adjusted PP-PASI change at week 8 for upadacitinib relative to historic placebo was -12.3 in favor of upadacitinib.
• Week 8 PP-PASI 50, PP-PASI 75, and Investigator Global Assessment responses were higher with upadacitinib than the historic placebo, at a respective 100% vs 16.1%, 65.0% vs 3.2%, and 45.0% vs 7.1%.
• Headache and acne were the most commonly reported adverse events, occurring in three patients each. Other side effects included upper respiratory infections, cold sore prodrome syndrome, dyslipidemia, and worsening of psoriatic arthritis symptoms after treatment was stopped (occurring in two patients each).

IN PRACTICE

“We really hope that we have been able to showcase an innovative trial design using historic controls, and one that is rarely used in dermatology,” reported David Gleeson, BM BCh, of St. John’s Institute of Dermatology, King’s College London, UK. “Alongside, we have detected a marked indication of potential clinical benefit, which will hopefully translate into real changes to your clinical practice in the future.” A definitive trial is now warranted and, “given the promising indication of effect size, we would argue that any future trial should consider being run with an active comparator arm rather than a placebo arm control.”

SOURCE 

The study was presented as an abstract at the European Academy of Dermatology and Venereology (EADV) 2026 Congress in Vienna, Austria, and has been accepted for publication in the British Journal of Dermatology. 

LIMITATIONS 

The study was not powered to show efficacy, and its short duration was not sufficient to determine the safety and tolerability of JAK inhibition in this patient population, among whom almost 80% are current or former smokers. 

DISCLOSURES 

The study was funded by the UK’s National Institute for Health and Care Research. Gleeson acknowledged educational support from Eli Lilly prior to the study’s initiation.