Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 21;15(8):e106361.
doi: 10.1136/bmjopen-2025-106361.

Janus kinase inhibitors in palmoplantar pustulosis: a mixed-methods feasibility (JAKPPPOT) trial protocol

David Gleeson  1 , Sarah Chapman  2 , Helen McAteer  3 , April Qin  1 , John Gregory  1 , Jade Pizzato  1 , Kingsley Powell  1 , Manpreet K Sagoo  1 , Weiyu Ye  1 , Ann Naylor  4 , Lucy Moorhead  1 , Andrew E Pink  1 , Richard Woolf  1 , Jonathan Barker  1 , James B Galloway  5 , Suzie Cro  6 , Satveer K Mahil  1 , C H Smith  7
Affiliations

Janus kinase inhibitors in palmoplantar pustulosis: a mixed-methods feasibility (JAKPPPOT) trial protocol

David Gleeson et al. BMJ Open. .

Abstract

Background: Palmoplantar pustulosis (PPP) is a rare, debilitating inflammatory skin disease involving painful pustules on the palms and soles. Janus kinase (JAK) inhibitors target pathways relevant to PPP disease biology but also confer a risk of major adverse cardiovascular events and malignancy in certain 'at risk' individuals; this includes those with PPP given prevalent smoking and cardiovascular risk factors in the PPP population. The feasibility of JAK inhibitor therapy for PPP requires assessment prior to a randomised controlled trial evaluation of drug efficacy and safety for this indication.

Methods and analysis: The 'Janus kinase inhibitors in palmoplantar pustulosis: a mixed-methods feasibility' trial is an open-label, single-centre, single-arm, mixed-methods feasibility trial of JAK inhibition in PPP (REC reference: 24/NE/0147; ISRCTN61751241). Participants (n=20) will receive 8 weeks of treatment with the JAK inhibitor upadacitinib ('Rinvoq', 30 mg, once daily). Qualitative semistructured interviews (up to n=40) will be undertaken with trial participants, trial decliners and healthcare professionals. The primary outcome will be a composite assessment of feasibility across three domains: recruitment, adherence and acceptability, using a mixed-methods analysis approach. Secondary objectives include the identification of trial recruitment optimisation strategies, using the 'Quintet Recruitment Intervention', and the generation of an indication of effect size on disease severity (measured using the Palmoplantar Pustulosis Psoriasis Area and Severity Index) to inform future sample size calculations. Historic placebo control data from the Anakinra for Pustular Psoriasis: Response in a Controlled Trial (National Institute of Health and Social Care reference: 13/50/17; Research Ethics Commitee reference: 16/LO/0436) will be used as the effect size comparator. Study recruitment will be undertaken over a 24-month period, commencing in November 2024.

Ethics and dissemination: This study has been approved by the Newcastle North Tyneside 2 Research Ethics Committee, 24/NE/0132. Our findings will inform the feasibility of a future adequately powered RCT evaluating the efficacy of JAK inhibitor therapy in PPP.

Trial registration number: ISRCTN61751241.

Keywords: Adult dermatology; Clinical trials; Feasibility Studies; Psoriasis.

PubMed Disclaimer

Conflict of interest statement

Competing interests: DG has received educational support from Lilly. HM works for the Psoriasis Association, a charity, and has received funding and/or speaker honoraria from Almirall, Abbvie, Dermal Laboratories, UCB, Janssen, Novartis, BMS, Boehringer Ingelheim and Medac Pharma. JBG has received speaker or advisory work fees from AbbVie, Alfasigma, Galapagos, Lilly, Pfizer and UCB and grant funding from AbbVie, Galapagos, Gilead, Glaxo-Smith Klein, Janssen-Cilag, Novartis, Pfizer, Sanofi, Takeda and UCB. LM has attended conferences, spoken at meetings and attended advisory boards for the following companies: Abbvie, Almirall, BMS, Galderma, Janssen Cilag, Leo, Lilly, Novartis, Sanofi, Pfizer and UCB. AEP has acted as investigator, advisor, speaker and/or received research or educational funding from Abbvie, Pfizer, Lilly, Amgen, Sanofi, Leo, Galderma, Janssen, Almirall, Novartis, BMS, UCB and BI. RW has been a consultant, advisory board member, investigator and/or speaker and received travel support for participation in congresses and/or (speaker) honoraria and/or research grants from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Galderma, Incyte, Janssen-Cilag, LEO Pharma A/S, Novartis, Pfizer, Sanofi and UCB. JB has attended advisory boards and/or received consultancy fees and/or spoken at sponsored symposia, and/or received grant funding from AbbVie, Amgen, Boehringer Ingelheim, Bristol-Meyers-Squibb, Johnson and Johnson, Lilly, Novartis and UCB. SKM reports departmental income from AbbVie, Almirall, Eli Lilly, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, Sanofi and UCB, outside the submitted work. CHS reports grants from a Medical Research Council-funded stratified medicine consortium with multiple industry partners (PSORT.org), grants from IMI (Horizon 2020)-funded European consortium with multiple industry partners (BIOMAP-IMI.eu, HIPPOCRATES-IMI.eu, grants from Open Targets (Wellcome Sanger Institute), and others from AbbVie, Novartis, Pfizer, Sanofi, Boehringer Ingelheim and Swedish Orphan Biovitrum, outside the submitted work and is Chair of UK guidelines on biologic therapy in psoriasis. The other authors reported no relevant disclosures.

Figures

Figure 1
Figure 1. Overview of the JAKPPPOT study design. JAKi, Janus kinase inhibitor; JAKPPPOT, Janus kinase inhibitors in palmoplantar pustulosiAnus Kinase inhibitors in PalmoPlantar PustulOsis: a mixed-methods feasibility; PPP, palmoplantar pustulosis; QRI, Quintet Recruitment Intervention.
Figure 2
Figure 2. An outline of the JAKPPPOT Quintet Recruitment Intervention phases. CI, chief investigator; JAKPPPOT, Janus kinase inhibitors in palmoplantar pustulosiAnus Kinase inhibitors in PalmoPlantar PustulOsis: a mixed-methods feasibility; TMG, trial management group.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Ramcharran D, Strober B, Gordon K, et al. The Epidemiology of Palmoplantar Pustulosis: An Analysis of Multiple Health Insurance Claims and Electronic Health Records Databases. Adv Ther. 2023;40:5090–101. doi: 10.1007/s12325-023-02669-w. - DOI - PMC - PubMed
    1. Benzian-Olsson N, Dand N, Chaloner C, et al. Association of Clinical and Demographic Factors With the Severity of Palmoplantar Pustulosis. JAMA Dermatol. 2020;156:1216–22. doi: 10.1001/jamadermatol.2020.3275. - DOI - PMC - PubMed
    1. Obeid G, Do G, Kirby L, et al. Interventions for chronic palmoplantar pustulosis: abridged Cochrane systematic review and GRADE assessments. Br J Dermatol. 2021;184:1023–32. doi: 10.1111/bjd.19560. - DOI - PubMed
    1. McCluskey D, Benzian-Olsson N, Mahil SK, et al. Single-cell analysis implicates TH17-to-TH2 cell plasticity in the pathogenesis of palmoplantar pustulosis. Journal of Allergy and Clinical Immunology. 2022;150:882–93. doi: 10.1016/j.jaci.2022.04.027. - DOI - PubMed
    1. Virtanen A, Spinelli FR, Telliez JB, et al. JAK inhibitor selectivity: new opportunities, better drugs? Nat Rev Rheumatol. 2024;20:649–65. doi: 10.1038/s41584-024-01153-1. - DOI - PubMed

Publication types

LinkOut - more resources