Sven Roy Quist

Background/Objectives: Cutaneous T-cell lymphomas (CTCL), most commonly mycosis fungoides and Sézary syndrome, are rare non-Hodgkin lymphomas. Advanced disease responds poorly to current treatments, highlighting the need for new molecularly targeted therapies. WEE1 is a central regulator of the G2/M checkpoint and S-phase progression and has emerged as a therapeutic target in several malignancies, yet it has not been systematically explored in CTCL. Methods: We screened a library of more than 2200 kinase inhibitors in CTCL cell lines and selected adavosertib for further study. Its effects were tested in four CTCL lines; primary keratinocytes and fibroblasts; patient-derived malignant CD4⁺ T cells and healthy donor CD4⁺ T cells; and a MyLa xenograft model, using viability, apoptosis, cell-cycle, Western blot, and phospho-protein array assays. Results: Adavosertib reduced viability at submicromolar IC₅₀ values (0.26–0.56 µM) across all four CTCL lines while largely sparing primary skin cells and was more active in malignant than in healthy donor CD4⁺ T cells. It induced apoptosis and cell-line-specific S-phase and/or G2/M accumulation, lowered WEE1 and phospho-CDK1 (Tyr15), and increased phospho-H2A.X. A phospho-protein array showed activation of checkpoint and stress signalling. In a preliminary xenograft experiment, adavosertib slowed MyLa tumour growth. Conclusions: These preclinical data identify WEE1 as a therapeutic target in CTCL and support further preclinical and early-phase clinical evaluation of adavosertib in this disease.

Atopic dermatitis (AD) is driven by type 2 inflammation, with interleukin-13 (IL-13) as one of the central operators. Lebrikizumab is a monoclonal antibody that inhibits IL-13 signalling. Adult patients with moderate-to-severe AD who received lebrikizumab in the TREATgermany registry until 12/2024 were selected, and patient characteristics as well as effectiveness and safety outcomes after 1, 3 and 6 months were evaluated. A total of 108 patients were initiated on lebrikizumab, with 80 having follow-up data available for this analysis (“registry cohort”). Forty-one patients were switched to lebrikizumab without a “washout period” from another advanced systemic therapy (“switchers”). The mean Eczema Area and Severity Index (EASI) decreased from 14.8 at baseline to 5.6 and 3.0 at month 3 and month 6 and was comparable between switchers and nonswitchers. Clinically meaningful improvements were also seen across all patient reported outcomes (PROs) equally in both groups, e.g. a decrease of the mean peak pruritus numeric rating scale (PP-NRS) from 6.6 to 3.8 and 3.4 and the Dermatology Life Quality Index (DLQI) from 11.9 to 4.9 and 4.8. Overall, adverse events (AEs) were reported for 26.6% of patients within the first 3. The most frequently reported AE was conjunctivitis or other ocular complications, reported in 13 patients (20.3%). 32 patients (40%) had an initial EASI≥16 and were comparable to patients in lebrikizumab phase 3 studies. In this “trial-like” cohort, EASI-75 and EASI-90 response rates were 60% and 26.7% at month 3 and 70% and 50% at month 6. Lebrikizumab shows effectiveness in routine care well comparable to observations made in randomized controlled trials.

Background: Atopic dermatitis (AD) substantially affects quality of life, yet standardized severity measures may not capture patient‐centred priorities, making systematic needs assessment essential for personalized care. Objectives: This study aimed to systematically assess and rank treatment needs in adults with moderate to severe AD, identify patient subgroups with distinct need profiles and evaluate how well these needs were met after 2 years of specialized dermatological care. Methods: In this prospective observational study from the TREATgermany registry, 697 adults with moderate to severe AD completed the validated Patient Benefit Index (PBI) at baseline (T1) and at 2‐year follow‐up (T2), capturing treatment goal importance and achievement. Subgroup analyses were performed based on age, sex, educational status and age at AD onset. Associations between clinical measures and perceived benefit were analysed. Results: The most frequently prioritized treatment goals were being free of itching (97.8% high agreement), regaining control of the disease (95.3%) and relief from skin burning (92.0%). The importance of itch reduction was not correlated with baseline pruritus intensity, and perceived benefit was more closely linked to relative clinical improvement than to absolute disease severity. Beyond these shared priorities, treatment needs varied across subgroups: older patients valued treatment safety and reduced dependence on medical care, women emphasized psychosocial and appearance‐related goals, individuals with lower educational status highlighted financial concerns and patients with adult‐onset AD prioritized diagnostic certainty and disease control. After 2 years, 96.6% of patients reported meaningful treatment benefit. Patient‐reported outcomes (POEM) were more strongly associated with perceived benefit than physician‐assessed measures (oSCORAD, EASI). Conclusion: Patient treatment needs in AD vary by demographic and clinical factors, with pruritus consistently rated as the highest priority. Patient‐reported outcomes align more closely with perceived benefit than physician assessments, underscoring the value of systematic needs assessments to guide individualized treatment decisions and shared decision‐making.

Background/Objectives: Cutaneous T-cell lymphomas (CTCL), most commonly mycosis fungoides and Sézary syndrome, are rare non-Hodgkin lymphomas. Advanced disease responds poorly to current treatments, highlighting the need for new molecularly tar-geted therapies. WEE1 is a central regulator of the G2/M checkpoint and S-phase progression and has emerged as a therapeutic target in several malignancies, yet it has not been systematically explored in CTCL. Methods: We screened a library of more than 2,200 kinase inhibitors in CTCL cell lines and selected adavosertib for further study. Its effects were tested in four CTCL lines, in primary keratinocytes and fibroblasts, in patient-derived malignant CD4⁺ T cells and healthy donor CD4⁺ T cells, and in a MyLa xenograft model, using viability, apoptosis, cell-cycle, western blot, and phospho-protein array assays. Results: Adavosertib reduced viability at submicromolar IC₅₀ values (0.26–0.56 µM) across all four CTCL lines while largely sparing primary skin cells and was more active in malignant than in healthy donor CD4⁺ T cells. It induced apoptosis and cell-line-specific S-phase and/or G2/M accumulation, lowered WEE1 and phospho-CDK1 (Tyr15), and increased phospho-H2A.X. A phospho-protein array showed activation of checkpoint and stress signalling. In vivo, adavosertib slowed MyLa xenograft growth. Conclusions: These preclinical data identify WEE1 as a therapeutic target in CTCL and support further preclinical and early-phase clinical evaluation of adavosertib in this disease.

The TREATgermany registry was set up in 2016. We provide results on long-term dupilumab therapy in adults with moderate and severe atopic dermatitis (AD) in a routine care setting. The analysis cohort of 294 patients is one of the largest cohorts with 2-year follow-up data on treatment effects of dupilumab obtained from an AD registry to date. We report the Harmonising Outcome Measures for Eczema (HOME) core outcome set. The Eczema Area Severity Index (EASI) 75 and EASI 90 response rates for patients on treatment at month 24 were 78.8% and 51.2%, respectively.

Artificial daylight photodynamic therapy with methyl aminolevulinate is an effective and almost painless treatment approach for actinic keratoses. The objective of the prospective, non-interventional, multicentre study ArtLight (NCT05725213) was to gain comprehensive insights into the cosmetic effect of methyl aminolevulinate-artificial daylight photodynamic therapy in patients with actinic keratoses using different artificial daylight systems under real-world conditions. The study enrolled patients with Olsen grade 1 or 2 actinic keratoses on the face and scalp in Germany. Patients were treated with methyl aminolevulinate-artificial daylight photodynamic therapy. The cosmetic effect was assessed via photodamage parameters (global score for photoaging, mottled pigmentation, tactile roughness, telangiectasias, fine lines). Each photodamage variable was recorded on a 5-point scale (0–4). In total, 224 patients (median age: 75.0 years [range 50–91], 85.3% male, 62.5% Olsen grade 2, 55.4% treatment-naive) were treated with methyl aminolevulinate-artificial daylight photodynamic therapy. At month 3, all 5 parameters of photoaging were significantly reduced from baseline (p < 0.001). The majority of patients (81.3%) and investigators (83.6%) rated the cosmetic result as good or very good. Beyond effective eradication of actinic keratoses, field-directed methyl aminolevulinate-artificial daylight photodynamic therapy can improve photoaging symptoms, including tactile roughness, mottled pigmentation, telangiectasis, and fine lines. Thus methyl aminolevulinate-artificial daylight photodynamic therapy provides additional benefits, particularly for patients concerned with cosmetic outcomes during or after treatment.

TREATgermany is an investigator-initiated prospective disease registry. It investigates physician- and patient-reported disease severity (Eczema Area and Severity Index (EASI), objective Scoring Atopic Dermatitis (oSCORAD), Investigator Global Assessment, Patient-Oriented Eczema Measure (POEM), Patient Global Assessment (PGA)), patient-reported symptoms (itch, sleep loss, depressive symptoms), therapy courses and dermatological quality of life (DLQI) in moderate-to-severe atopic dermatitis with SCORAD > 20. 1,134 atopic dermatitis patients (mean age 41.0 ± 14.7 years, 42.5% females) were enrolled by 40 German recruiting sites (dermatological clinics and practices) between June 2016 and April 2021. The current analysis focuses on itch scores obtained with a numerical rating scale (NRS)) documented for the previous 3 days prior to baseline visit. The results show that 97.2% (1,090 of 1,121) patients experienced itch. Itch severity correlated moderately with severity of atopic dermatitis oSCORAD (rho = 0.44 (0.39–0.48)) and EASI score (rho = 0.41 (0.36–0.46)). A strong correlation was found with self-reported disease severity as PGA (rho = 0.68 (0.65–0.71)), POEM sum score (rho = 0.66 (0.63–0.69)) and dermatological quality of life impairment DLQI (rho = 0.61 (0.57–0.65)). Itch as a subjective complaint is more closely correlated with patient-reported outcomes than with objective assessments by the physician.

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