Drug survival of biologic therapies for palmoplantar pustulosis: A nationwide study.

BACKGROUND: Biological therapies have established efficacy in psoriasis vulgaris. However, palmoplantar pustulosis (PPP) has proven difficult to treat, and data on drug survival in these patients remain scarce. OBJECTIVE: To investigate drug survival of biological treatments in a nationwide cohort of patients with PPP. METHODS: We included all patients treated for PPP with a biologic from a prospective Danish nationwide registry between 2007 and 2019. Descriptive statistics were reported. Drug survival was calculated for all patients and specified for the most frequently used biologics. Drug survival was reported as median time to discontinuation. Kaplan-Meier plots were used to visualize drug survival. Trajectories of Dermatology Life Quality Index (DLQI) scores were plotted by interpolating between the different visits with a dermatologist for each treatment course. RESULTS: We identified 85 individual patients who received biological therapy for PPP across 194 treatment courses during follow-up. Of the included treatment courses, 151 (77.8%) were discontinued. The most frequent cause of discontinuation was ineffective response to treatment (54.3%), while 18.5% of courses were discontinued due to adverse events. The median drug survival across all therapies for PPP was 9.3 (Inter quartile range (IQR), 3.9-25.6) months. Ustekinumab demonstrated the longest median time to discontinuation of 14.6 (IQR, 9.1-51.8) months. The proportion of bio-naive patients in treatment at 12 months were according to drug 47.9% for adalimumab, 64.3% for ustekinumab and 40.0% for secukinumab. For bio-experienced, it was 58.2% adalimumab, 54.5% for ustekinumab and 51.4% for secukinumab. CONCLUSIONS: The treatment of PPP poses significant challenges, with limited drug survival observed across all therapies regardless of prior experience with biologics. Ustekinumab demonstrated the longest median drug survival. Notably, patients discontinuing therapy due to inefficacy exhibited higher DLQI scores, highlighting the importance of personalized treatment selection and timely consideration of therapy changes when inefficacy is established.

The dynamics of gene expression of interleukin-19 and interleukin-20 and their receptors in psoriasis.

BACKGROUND: Interleukin (IL)-20 and IL-19 are recently discovered members of the IL-10 family of cytokines. The skin of transgenic mice overexpressing IL-20 shows histological changes resembling some of those seen in psoriasis, i.e. thickened epidermis, hyperkeratosis and a compact stratum corneum. IL-19 and IL-20, as well as their receptor complexes, IL-20Ralpha/IL-20Rbeta and IL-22Ralpha/IL-20Rbeta, are expressed in human skin. OBJECTIVES: To study the dynamics of IL-19 and IL-20 gene expression as well as the expression of their receptor subunits in psoriatic skin lesions. METHODS: Punch biopsies from patients with plaque-type psoriasis were collected before, during and after 28 days of treatment with either calcipotriol or ciclosporin (CsA). IL-20, IL-19, IL-20Ralpha, IL-20Rbeta and IL-22Ralpha mRNA expression were determined by quantitative reverse transcriptase-polymerase chain reaction. RESULTS: We found IL-19 and IL-20 mRNA expression in lesional psoriatic skin to be strongly upregulated compared with nonlesional psoriatic skin by a factor of 65 and 22, respectively. In contrast to previous reports, IL-20Ralpha and IL-20Rbeta mRNA levels showed a modest but statistically significant decrease in lesional psoriatic skin compared with nonlesional psoriatic skin. During treatment with calcipotriol or CsA, IL-19 and IL-20 mRNA levels decrease in accordance with the clinical improvement of psoriasis. Neither IL-19, IL-20, nor receptor subunit mRNA expression in lesional psoriatic skin reaches the levels of nonlesional skin during this short-term treatment. These findings are in line with the residual disease activity observed at the end of treatment. CONCLUSIONS: The increased IL-19 and IL-20 mRNA expression levels in lesional psoriatic skin suggest that these two cytokines play a role in the pathogenesis of psoriasis. An imbalance in the receptor complexes for IL-19 and IL-20 might contribute to their suspected pathogenic effects.