Efficacy and Safety of Tofacitinib in Palmoplantar Pustulosis: A Retrospective Study
DOI:
https://doi.org/10.2340/actadv.v105.44083Keywords:
Palmoplantar pustulosis, Janus kinase inhibitors, Retrospective study, Efficacy, Safety, Inflammatory markersAbstract
Palmoplantar pustulosis (PPP) remains a therapeutic challenge with limited options, and recurrence is a major issue for traditional systemic therapies and biologics. Data on long-term efficacy, safety, and relapse of Janus kinase inhibitors in PPP are limited. Drug efficacy, safety, and recurrence was retrospectively evaluated in 29 PPP patients treated with tofacitinib from January 2022 to June 2024. Disease severity and efficacy were assessed using the Palmoplantar Pustular Psoriasis Area and Severity Index (PPPASI) and Palmoplantar Pustular Psoriasis Physician’s Global Assessment (PPP PGA) at baseline, week 4, and week 12, with a minimum 6-month follow-up. PPP-related haematological inflammatory indicators, including plateletcrit (PCT), pan-immune-inflammation value (PIV), neutrophil/lymphocyte ratio (NLR), and monocyte/lymphocyte ratio (MLR), were also evaluated. By week 12, mean PPPASI score significantly decreased from 18.62 to 6.17 (p < 0.001), with 72.41% achieving PPPASI-50 and 62.1% achieving PPP PGA ≤ 1. Mild adverse events (gastric discomfort) occurred in 6.9% of patients. During a mean 12.2-month follow-up, 27.6% relapsed, while 34.5% maintained clearance without medication. Disease severity-related haematologic indicators, PCT, and PIV improved significantly. Tofacitinib demonstrates significant efficacy and a favourable safety profile in PPP, warranting consideration as a therapeutic option, though larger prospective studies are needed to confirm long-term outcomes.
Downloads
References
Misiak-Galazka M, Zozula J, Rudnicka L. Palmoplantar pustulosis: recent advances in etiopathogenesis and emerging treatments. Am J Clin Dermatol 2020; 21: 355–370. DOI: https://doi.org/10.1007/s40257-020-00503-5
Mrowietz U, van de Kerkhof PC. Management of palmoplantar pustulosis: do we need to change? Br J Dermatol 2011; 164: 942–946. DOI: https://doi.org/10.1111/j.1365-2133.2011.10233.x
Kubota K, Kamijima Y, Sato T, Ooba N, Koide D, Iizuka H, et al. Epidemiology of psoriasis and palmoplantar pustulosis: a nationwide study using the Japanese national claims database. BMJ Open 2015; 5: e006450. DOI: https://doi.org/10.1136/bmjopen-2014-006450
Michaëlsson G, Kristjánsson G, Pihl Lundin I, Hagforsen E. Palmoplantar pustulosis and gluten sensitivity: a study of serum antibodies against gliadin and tissue transglutaminase, the duodenal mucosa and effects of gluten-free diet. Br J Dermatol 2007; 156: 659–666. DOI: https://doi.org/10.1111/j.1365-2133.2006.07725.x
Akiyama T, Seishima M, Watanabe H, Nakatani A, Mori S, Kitajima Y. The relationships of onset and exacerbation of pustulosis palmaris et plantaris to smoking and focal infections. J Dermatol 1995; 22: 930–934. DOI: https://doi.org/10.1111/j.1346-8138.1995.tb03948.x
Yamamoto T. Triggering role of focal infection in the induction of extra-palmoplantar lesions and pustulotic arthro-osteitis associated with palmoplantar pustulosis. Adv Otorhinolaryngol 2011; 72: 89–92. DOI: https://doi.org/10.1159/000324620
Muro M, Kawakami H, Matsumoto Y, Abe N, Tsuboi R, Okubo Y. Topical combination therapy with vitamin D3 and corticosteroid ointment for palmoplantar pustulosis: a prospective, randomized, left-right comparison study. J Dermatolog Treat 2016; 27: 51–53. DOI: https://doi.org/10.3109/09546634.2015.1052036
Umezawa Y, Nakagawa H, Tamaki K. Phase III clinical study of maxacalcitol ointment in patients with palmoplantar pustulosis: a randomized, double-blind, placebo-controlled trial. J Dermatol 2016; 43: 288–293. DOI: https://doi.org/10.1111/1346-8138.13064
Engin B, Oguz O. Evaluation of time-dependent response to psoralen plus UVA (PUVA) treatment with topical 8-methoxypsoralen (8-MOP) gel in palmoplantar dermatoses. Int J Dermatol 2005; 44: 337–339. DOI: https://doi.org/10.1111/j.1365-4632.2004.02153.x
Su LN, Ren J, Cheng SM, Liu JL, Ding YF, Zhu NW. UVA1 vs. narrowband UVB phototherapy in the treatment of palmoplantar pustulosis: a pilot randomized controlled study. Lasers Med Sci 2017; 32: 1819–1823. DOI: https://doi.org/10.1007/s10103-017-2280-0
Sevrain M, Richard MA, Barnetche T, Rouzaud M, Villani AP, Paul C, et al. Treatment for palmoplantar pustular psoriasis: systematic literature review, evidence-based recommendations and expert opinion. J Eur Acad Dermatol Venereol 2014; 28: 13–16. DOI: https://doi.org/10.1111/jdv.12561
Skov L, Beurskens FJ, Zachariae CO, Reitamo S, Teeling J, Satijn D, et al. IL-8 as antibody therapeutic target in inflammatory diseases: reduction of clinical activity in palmoplantar pustulosis. J Immunol 2008; 181: 669–679. DOI: https://doi.org/10.4049/jimmunol.181.1.669
Tauber M, Viguier M, Alimova E, Petit A, Lioté F, Smahi A, et al. Partial clinical response to anakinra in severe palmoplantar pustular psoriasis. Br J Dermatol 2014; 171: 646–649. DOI: https://doi.org/10.1111/bjd.13012
Cornelius V, Wilson R, Cro S, Barker J, Burden D, Griffiths CEM, et al. A small population, randomised, placebo-controlled trial to determine the efficacy of anakinra in the treatment of pustular psoriasis: study protocol for the APRICOT trial. Trials 2018; 19: 465. DOI: https://doi.org/10.1186/s13063-018-2841-y
Mrowietz U, Bachelez H, Burden AD, Rissler M, Sieder C, Orsenigo R, et al. Secukinumab for moderate-to-severe palmoplantar pustular psoriasis: results of the 2PRECISE study. J Am Acad Dermatol 2019; 80: 1344–1352. DOI: https://doi.org/10.1016/j.jaad.2019.01.066
Pinter A, Wilsmann-Theis D, Peitsch WK, Mössner R. Interleukin-17 receptor A blockade with brodalumab in palmoplantar pustular psoriasis: report on four cases. J Dermatol 2019; 46: 426–430. DOI: https://doi.org/10.1111/1346-8138.14815
Bissonnette R, Maari C, Tsianakas A, Reid D, McCutchan S, Baumgartner S, et al. A randomized, double-blind, placebo-controlled, phase 2a study to evaluate the efficacy and safety of RIST4721 in subjects with palmoplantar pustulosis. Dermatol Ther (Heidelb) 2021; 11: 2179–2193. DOI: https://doi.org/10.1007/s13555-021-00632-7
Okubo Y, Kobayashi S, Murakami M, Sano S, Kikuta N, Ouchi Y, et al. Efficacy and safety of brodalumab, an anti-interleukin-17 receptor A monoclonal antibody, for palmoplantar pustulosis: 16-week results of a randomized clinical trial. Am J Clin Dermatol 2024; 25: 837–847. DOI: https://doi.org/10.1007/s40257-024-00876-x
Terui T, Kobayashi S, Okubo Y, Murakami M, Hirose K, Kubo H. Efficacy and safety of guselkumab, an anti-interleukin 23 monoclonal antibody, for palmoplantar pustulosis: a randomized clinical trial. JAMA Dermatol 2018; 154: 309–316. DOI: https://doi.org/10.1001/jamadermatol.2017.5937
Bissonnette R, Poulin Y, Bolduc C, Maari C, Provost N, Syrotuik J, et al. Etanercept in the treatment of palmoplantar pustulosis. J Drugs Dermatol 2008; 7: 940–946.
Chapman S, Kwa M, Gold LS, Lim HW. Janus kinase inhibitors in dermatology: Part I. A comprehensive review. J Am Acad Dermatol 2022; 86: 406–413. DOI: https://doi.org/10.1016/j.jaad.2021.07.002
Xu Q, Wang X, Yang A, Wei G. Refractory palmoplantar pustulosis successfully treated with JAK inhibitor tofacitinib: a case series. Infect Drug Resist 2023; 16: 5165–5172. DOI: https://doi.org/10.2147/IDR.S421299
Li C, Li Z, Cao Y, Li L, Li F, Li Y, et al. Tofacitinib for the treatment of nail lesions and palmoplantar pustulosis in synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome. JAMA Dermatol 2021; 157: 74–78. DOI: https://doi.org/10.1001/jamadermatol.2020.3095
Koga T, Sato T, Umeda M, Fukui S, Horai Y, Kawashiri SY, et al. Successful treatment of palmoplantar pustulosis with rheumatoid arthritis, with tofacitinib: impact of this JAK inhibitor on T-cell differentiation. Clin Immunol 2016; 173: 147–148. DOI: https://doi.org/10.1016/j.clim.2016.10.003
Fan Y, Yin R. Janus kinase inhibitor tofacitinib successfully treated palmoplantar pustulosis after switching from secukinumab: a case report and review of the literature. Int Immunopharmacol 2024; 139: 112762. DOI: https://doi.org/10.1016/j.intimp.2024.112762
Haynes D, Topham C, Hagstrom E, Greiling T. Tofacitinib for the treatment of recalcitrant palmoplantar pustulosis: a case report. Australas J Dermatol 2020; 61: e108–e110. DOI: https://doi.org/10.1111/ajd.13117
Du N, Yang J, Zhang Y, Lv X, Cao L, Min W. Successful treatment of refractory palmoplantar pustulosis by upadacitinib: report of 28 patients. Front Med (Lausanne) 2024; 11: 1476793. DOI: https://doi.org/10.3389/fmed.2024.1476793
Wang YA, Rosenbach M. Successful treatment of refractory tumor necrosis factor inhibitor-induced palmoplantar pustulosis with tofacitinib: report of case. JAAD Case Rep 2020; 6: 115–118. DOI: https://doi.org/10.1016/j.jdcr.2019.12.006
Ning X, Wu C, Song B, Wang HM, Jin HZ. Evaluation of hematological inflammatory parameters in patients with palmoplantar pustulosis. Int J Dermatol 2024; 10.1111/ijd.17230. DOI: https://doi.org/10.1111/ijd.17230
Watanabe T, Yamaguchi Y. Author reply to “regarding “retrospective study of the clinical significance of the neutrophil-to-lymphocyte ratio in 79 patients with palmoplantar pustulosis””. J Dermatol 2025; 52: e187–e188. DOI: https://doi.org/10.1111/1346-8138.17440
Terui T, Okubo Y, Kobayashi S, Sano S, Morita A, Imafuku S, et al. Efficacy and safety of apremilast for the treatment of Japanese patients with palmoplantar pustulosis: results from a phase 2, randomized, placebo-controlled study. Am J Clin Dermatol 2023; 24: 837–847. DOI: https://doi.org/10.1007/s40257-023-00788-2
Wilsmann-Theis D, Kromer C, Gerdes S, Linker C, Magnolo N, Sabat R, et al. A multicentre open-label study of apremilast in palmoplantar pustulosis (APLANTUS). J Eur Acad Dermatol Venereol 2021; 35: 2045–2050. DOI: https://doi.org/10.1111/jdv.17441
Terui T, Okubo Y, Kobayashi S, Sano S, Morita A, Imafuku S, et al. Author correction: Efficacy and safety of apremilast for the treatment of Japanese patients with palmoplantar pustulosis: results from a phase 2, randomized, placebo-controlled study. Am J Clin Dermatol 2024; 25: 165–167. DOI: https://doi.org/10.1007/s40257-023-00825-0
Banerjee S, Biehl A, Gadina M, Hasni S, Schwartz DM. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs 2017; 77: 521–546. DOI: https://doi.org/10.1007/s40265-017-0701-9
Maronese CA, Valenti M, Moltrasio C, Romagnuolo M, Ferrucci SM, Gilliet M, et al. Paradoxical psoriasis: an updated review of clinical features, pathogenesis, and treatment options. J Invest Dermatol 2024; 144: 2364–2376. DOI: https://doi.org/10.1016/j.jid.2024.05.015
Published
How to Cite
License
Copyright (c) 2025 Shuang Lyu, Xiaotong Xue, Na Wang, Hong Liu, Furen Zhang

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All digitalized ActaDV contents is available freely online. The Society for Publication of Acta Dermato-Venereologica owns the copyright for all material published until volume 88 (2008) and as from volume 89 (2009) the journal has been published fully Open Access, meaning the authors retain copyright to their work.
Unless otherwise specified, all Open Access articles are published under CC-BY-NC licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material for non-commercial purposes, provided proper attribution to the original work.