Georgios Kokolakis

Background: We report the first study of anumigilimab, a novel anti‐G‐CSFR antibody, in patients with neutrophil‐driven skin diseases [hidradenitis suppurativa (HS) and palmoplantar pustulosis (PPP)]. Methods: This phase 1b, open‐label, repeat‐dose study (NCT03972280) comprised 15‐week treatment and 9‐week follow‐up periods. Enrolled patients had International HS Severity Score System (IHS4) score ≥4 or PPP Area and Severity Index (ppPASI) score ≥12. After ≥10 patients completed anumigilimab 0.3 mg/kg IV at 21‐day intervals (Cohort 1), pharmacokinetic/pharmacodynamic modelling determined the Cohort 2 dose (0.6 mg/kg). Primary endpoints were treatment‐emergent adverse events (TEAEs). Secondary endpoints were pharmacokinetics and immunogenicity. Exploratory endpoints were pharmacodynamics and clinical response. Results: Of 39 patients (HS, n = 22; PPP, n = 17), 33 patients (84.6%) experienced 198 TEAEs. Sixteen patients (41.0%) experienced 70 anumigilimab‐related TEAEs; the most common were fatigue and neutropenia (both n = 7), which resolved spontaneously, and no association between neutropenia and infections was observed. No deaths or serious treatment‐related TEAEs occurred. Presence of antidrug antibodies was negligible. Anumigilimab exposure and absolute neutrophil count reduction (pharmacodynamic endpoint) were dose dependent. In signal‐finding exploratory analyses, 57.9% of patients with HS ( n = 11/19 with data at Week 15) achieved ≥50% HS Clinical Response, IHS4 score decreased by 40.3%, and patients with PPP experienced a 40.4% reduction in ppPASI score. These clinical responses were not dose dependent, possibly due to imbalanced baseline characteristics and small sample size. Conclusions: Anumigilimab was generally well tolerated in patients with HS or PPP, with no serious treatment‐related safety concerns, and demonstrated dose‐dependent pharmacology. While clinical responses in HS and PPP were observed, it should be noted that these observations were exploratory and signal‐finding in nature. Importantly, the study was not powered to statistically confirm efficacy and lacked a placebo control, underscoring the need for future randomized, placebo‐controlled trials to validate these preliminary signal‐finding observations.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder affecting intertriginous areas. Long‐standing HS can undergo malignant transformation into squamous cell carcinoma (SCC), particularly in the perineal and gluteal regions. We report a 54‐year‐old man with severe, treatment‐refractory HS complicated by an aggressive verrucous SCC in the perianal area. The patient underwent multiple systemic therapies—including adalimumab, secukinumab, and bimekizumab—combined with several surgical interventions for the HS. While adalimumab led to partial improvement of HS, concerns exist about its potential association with SCC development. Upon SCC recurrence, the patient was treated with the PD‐1 inhibitor cemiplimab, which triggered a severe HS exacerbation and complicated the clinical course. Subsequently, IL‐17 inhibitors were used to better control HS inflammation during oncologic management. Ultimately, radical surgery was necessary to achieve complete tumor excision. Patients with long‐standing HS should be regularly monitored for suspicious lesions, and atypical or non‐healing wounds should be promptly biopsied to enable early detection of malignant transformation. The management of coexisting HS and SCC is complex, as demonstrated in this case by the challenges of selecting and timing immunomodulatory therapies that adequately control inflammation without increasing cancer progression risk or provoking severe disease flares. Multidisciplinary, individualized treatment and close follow‐up are essential to optimize outcomes in these challenging cases.

Introduction Tildrakizumab, an anti-IL-23p19 antibody, is registered for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. Its effectiveness in specific patient subgroups—e.g. those with high body weight, high disease burden, involvement of high-impact areas or older patients—is often underrepresented in randomised clinical trials and better captured in real-world settings. To address this gap, the present meta-analysis was undertaken to synthesise data from four observational studies conducted in Germany (TILOT, TiGER, TIL-SENIOR, TIL-TWO), each focusing on distinct psoriasis populations. Methods This meta-analysis of four prospective multicentre non-interventional studies evaluated the effectiveness and safety of tildrakizumab in different patient populations with moderate-to-severe plaque psoriasis. Outcome parameters assessed at baseline, week 16 and 28 included absolute Psoriasis Area Severity Index (PASI) values, proportion of patients with PASI < 1, < 3, < 5, PASI 75, PASI 90 and PASI 100, body surface area (BSA), Physician’s Global Assessment (PGA) 0/1 and Dermatology Life Quality Index (DLQI) 0/1. The meta-analysis was conducted using a random effects model. Results The meta-analysis included 1504 patients. The course of the absolute PASI and BSA and the proportion of patients achieving PASI < 3, PASI 75, 90, 100, PGA 0/1 and DLQI 0/1 at week 28 was comparable across all four studies. Overall, mean PASI scores decreased from 16.5 (95% confidence intervals (CI) 15.8–17.3) at baseline to 2.8 (95% CI 2.5–3.0) at week 28. The proportion of patients with PGA 0/1 and DLQI 0/1 increased from 1.8% and 3.7% at baseline to 63.5% and 51.2% at week 28, respectively. No new safety signals were identified. Conclusions Tildrakizumab showed consistent effectiveness across different study populations. Substantial effectiveness was achieved over 28 weeks. Safety results were comparable across populations, without outliers in older patients or patients with higher disease burden. Graphical abstract available for this article.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with significant diagnostic delays and impact on quality of life. Current guidelines prioritize antibiotics as first‐line therapy, but experts increasingly recognize the need for earlier targeted therapy intervention to prevent irreversible scarring and tunnel formation. To establish consensus on clinical scenarios during the 14th European Hidradenitis Suppurativa Foundation Conference in February 2025, 54 HS experts participated in a Delphi consensus, using a Likert scale (−5 to +5) to vote on 16 statements concerning first‐line therapy criteria with biologics and/or small molecules for eligible patients. Seventy‐eight HS experts were invited, and 54 participated via hybrid onsite and electronic voting. Experts rated 16 pre‐defined statements regarding first‐line use of biologics and/or small molecules for HS using a Likert scale (−5 to +5). Agreement metrics were stratified as majority agreement (≥70%, median 3.0–3.5), consensus (≥75%, median 3.5–4.5), and strong consensus (≥90%, median ≥4.5). Statements were subsequently ranked for clinical relevance. Strong consensus was reached for patients contraindicated for antibiotics, rapid disease progressors and those with severe disease. Consensus also supported upgrading patients with moderate disease (IHS4 ≥ 4), frequent flares (≥3 in 12 weeks), multiple affected areas and specific phenotypes including anogenital involvement. Strong consensus emerged for syndromic HS and for patients with inflammatory comorbidities such as inflammatory bowel disease and arthritis. Paediatric patients with a positive family history and moderate disease were also considered candidates for first‐line biologics or small molecules. This consensus provides evidence‐based criteria for upgrading HS patients to first‐line biologic therapy, reflecting expert practices across Europe aimed at preventing irreversible disease progression. The results support a ‘hit hard and early’ approach to minimize scarring and tunnel formation, although prospective studies are still needed to validate these expert‐driven recommendations.

Summary: Background and objectives: Psoriasis can result in reduced quality of life, work productivity loss, and a significant restriction in non‐professional activities. This study investigates the effects of long‐term treatment with adalimumab regarding work ability, non‐professional activities, and health‐related quality of life in a large real‐word population in Germany. Patients and methods: Single‐arm, multicenter non‐interventional study to document routine care data for up to 5 years in adult patients with psoriasis after initiation of adalimumab. Results: Baseline data was collected for 4,793 (62.1 % male) patients with a mean (± SD) age of 47.5 ± 13.11 years. The number of days with restrictions in non‐professional activities was much higher than in professional activities. Under adalimumab, the psoriasis‐related number of days unfit for work and number of days with restrictions in non‐professional activities significantly decreased. Correlation analyses showed that psoriatic arthritis, disease severity (PASI > 10), and impairment of quality of life (DLQI > 10) are associated with restrictions in non‐professional activities. Health‐related quality of life improved over the observed time but remained reduced in patients with restrictions in non‐professional activities. Conclusions: Long‐term treatment with adalimumab had a favorable impact on clinical outcomes, employment‐related aspects, practice of non‐professional activities, and health‐related quality of life in psoriasis patients.

Background: Hidradenitis suppurativa (HS) is a chronic, painful inflammatory skin disease. There is a need to evaluate how patients experience their disease.Objectives: The HS Uncovered survey was conducted to understand patient activation, the patient journey and burden of disease.Methods: HS Uncovered was a real‐world, quantitative, online survey completed by adults who self‐reported a diagnosis/suspected diagnosis of HS. The survey included patient‐reported outcome measures (PROMs) and non‐PROM‐related questions and was conducted between December 2022 to March 2023 in six countries (US, UK, Germany, France, ltaly, Spain). PROMs included the Patient Activation Measure (PAM13; primary endpoint), Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment (WPAI) and Hospital Anxiety and Depression Scale (HADS) tools (Spain excluded from PROM analyses).Results: Overall, 656 participants were included (N = 505, diagnosed HS; N = 151, suspected HS). Of 425 diagnosed participants, 66% reported high (level 3/4) PAM13 scores. A very large (DLQI score 11–20) and extremely large (DLQI score 21–30) effect of HS on QoL was reported by 41% and 28% of participants, respectively. A very large to extremely large effect of HS on QoL (DLQI score 11–30) was reported by 67% and 73% of patients with level 3 and 4 PAM13 scores, respectively. Overall, 53% and 29% of diagnosed participants reported abnormal anxiety and depression, respectively. The percentage of work impairment due to HS in employed diagnosed participants (N = 302) was 52%. Of diagnosed females, 52% considered HS a concern for family planning. Overall (N = 656), 58% of participants considered pain relief the most important treatment feature.Conclusions: Despite participants having high activation levels, HS had a negative impact on QoL, mental health, work and activity. There is an unmet need for effective treatments that provide sustained pain reduction and improve work productivity in HS.

Health-related quality of life (HRQoL) is reduced in atopic dermatitis and psoriasis. Several factors impact HRQoL including sociodemographic and skin disease-related characteristics, health behaviours, cardiometabolic comorbidities, and psychological conditions. However, their differential and unique effects on HRQoL are not well studied. In this cross-sectional online survey, adult patients with atopic dermatitis (n = 155) or psoriasis (n = 246) provided data on features of their respective skin diseases, health behaviours, and cardiometabolic comorbidities. Validated self-report measures assessed HRQoL, psychopathology (Patient Health Questionnaire-4), and stress (Perceived Stress Scale). Linear regression analyses were used to determine key predictors of HRQoL. In atopic dermatitis, linear regression analyses revealed that self-rated disease severity (Patient-Oriented Eczema Measure), anxiety, and stress were significant predictors of the Dermatology Life Quality Index (DLQI), explaining 59% of the variance. In psoriasis, disease severity (Psoriasis Symptoms and Signs Diary) and depression significantly predicted DLQI, with an explained variance of 57%. Health behaviours and cardiometabolic comorbidities did not impact DLQI scores. While skin disease severity is the most important determinant of HRQoL, stress and anxiety are important in atopic dermatitis, whereas depression is relevant in psoriasis. These findings hold implications for both clinical practice and research.

Shame is a complex emotion with different facets. Skin shame is a specific aspect of body shame, which involves the skin perceived as inferior or flawed. Its role in atopic dermatitis (AD) and psoriasis is not well investigated. This explorative study pursued three objectives: First, the comparative analysis of shame and its facets in AD and psoriasis. Second, analysis of the association of skin shame with other shame facets, depression, and anxiety. Third, exploration of the unique impact of shame and its different facets on quality of life (QoL) in AD and psoriasis patients. This cross-sectional online survey encompassing German-speaking patients included several self-report measures on skin and general shame, depression, and anxiety as well as the Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and Psoriasis Symptoms and Signs Diary (PSSD). Data from 413 adult participants with AD (N = 162) or psoriasis (N = 251) were analyzed. There were no significant differences in skin or general shame, depression, or anxiety between those with AD or psoriasis. Skin shame as well as other aspects of shame were associated with younger age, female sex, depression, anxiety, and QoL. Analysis of AD and psoriasis subsamples revealed significant correlations of disease severity with skin shame, depression, anxiety, and DLQI. Hierarchical linear regression analyses indicated that skin shame was the second most important determinant of QoL after self-assessed disease severity. Systematic consideration of shame in AD and psoriasis is necessary in order to effectively reduce disease burden and enhance QoL.