TY  - JOUR
AB  - IMPORTANCE: Psoriasis is a chronic inflammatory skin disease with unmet needs for tailored treatment and therapy de-escalation strategies. OBJECTIVE: To evaluate early intervention with and prolonging the dosing interval for guselkumab, a p19 subunit-targeted interleukin (IL)-23 inhibitor, in patients with moderate to severe psoriasis. DESIGN, SETTING, AND PARTICIPANTS: The GUIDE clinical trial is an ongoing phase 3b, randomized, double-blinded trial conducted across 80 centers in Germany and France comprising 3 parts evaluating the impact of early disease intervention, prolonged dosing interval, and maintenance of response following treatment withdrawal among adults with moderate to severe plaque psoriasis. In study part 2, reported herein, first and last patient visits were September 2019 and March 2022, respectively. INTERVENTIONS: In GUIDE part 1 (week [W]0-W28), patients received guselkumab, 100 mg, at W0, W4, W12, and W20. Those achieving a Psoriasis Area and Severity Index (PASI) of 0 at both W20 and W28 were termed super responders (SRes). In part 2 (W28-W68), SRes were randomized to guselkumab, 100 mg, every 8 weeks or every 16 weeks; non-SRes continued open-label guselkumab every 8 weeks. MAIN OUTCOMES AND MEASURES: Primary objective was to demonstrate noninferiority (with a 10% margin) of guselkumab every 16 weeks vs every 8 weeks dosing among SRes for maintenance of disease control (PASI <3 at W68). Biomarker substudies assessed immunologic effects in skin and blood. RESULTS: Overall, 822 patients received guselkumab in part 2 (297 [36.1%] SRes [every 8 weeks/every 16 weeks; n = 148/n = 149] and 525 [63.9%] non-SRes). Among SRes, mean (SD) age was 39.4 (14.1) years, 95 (32.0%) were female, and 202 (68.0%) were male. The primary end point of noninferiority for guselkumab every 16 weeks vs every 8 weeks in SRes was met (P = .001), with 91.9% (137/149; 90% CI, 87.3%-95.3%) of SRes receiving every 16 weeks and 92.6% (137/148; 90% CI, 88.0%-95.8%) of SRes receiving dosing every 8 weeks having PASI lower than 3 at W68. Clinical effects corresponded with immunologic changes; skin CD8-positive tissue-resident memory T (TRM)-cell count decreased quickly from baseline, remaining low in both dosing groups. Similarly, serum IL-17A, IL-17F, IL-22, and β defensin (BD)-2 levels decreased significantly from baseline, remaining low in both dosing groups to W68. Guselkumab was well-tolerated; no new safety signals were identified. CONCLUSIONS AND RELEVANCE: Psoriasis treatment guidelines lack or provide inconsistent advice on patient stratification and treatment de-escalation. We present the first randomized trial providing evidence that, in patients with early complete skin clearance at 2 consecutive visits (W20 and W28), extending the guselkumab dosing interval may control disease activity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03818035.
AU  - Eyerich, K.*
AU  - Asadullah, K.*
AU  - Pinter, A.*
AU  - Weisenseel, P.*
AU  - Reich, K.*
AU  - Paul, C.*
AU  - Sabat, R.*
AU  - Wolk, K.*
AU  - Eyerich, S.
AU  - Lauffer, F.
AU  - Angsana, J.*
AU  - Taut, F.J.H.*
AU  - Köhler, K.*
AU  - Chen, Y.*
AU  - Sendecki, J.*
AU  - Leung, M.W.L.*
AU  - Wegner, S.*
AU  - Personke, Y.*
AU  - Gomez, M.*
AU  - Krüger, N.*
AU  - Tabori, S.*
AU  - Schäkel, K.*
C1  - 71369
C2  - 56079
CY  - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa
TI  - Noninferiority of 16-week vs 8-week guselkumab dosing in super responders for maintaining control of psoriasis: The GUIDE randomized clinical trial.
JO  - JAMA Dermatol.
PB  - Amer Medical Assoc
PY  - 2024
SN  - 2168-6084
ER  - 

TY  - JOUR
AB  - Importance: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease and is driven by a complex pathophysiology underlying highly heterogeneous phenotypes. Current advances in precision medicine emphasize the need for stratification. Objective: To perform deep phenotyping and identification of severity-associated factors in adolescent and adult patients with AD. Design, Setting, and Participants: Cross-sectional data from the baseline visit of a prospective longitudinal study investigating the phenotype among inpatients and outpatients with AD from the Department of Dermatology and Allergy of the University Hospital Bonn enrolled between November 2016 and February 2020. Main Outcomes and Measures: Patients were stratified by severity groups using the Eczema Area and Severity Index (EASI). The associations of 130 factors with AD severity were analyzed applying a machine learning-gradient boosting approach with cross-validation-based tuning as well as multinomial logistic regression. Results: A total of 367 patients (157 male [42.8%]; mean [SD] age, 39 [17] years; 94% adults) were analyzed. Among the participants, 177 (48.2%) had mild disease (EASI ≤7), 120 (32.7%) had moderate disease (EASI >7 and ≤ 21), and 70 (19.1%) had severe disease (EASI >21). Atopic stigmata (cheilitis: odds ratio [OR], 8.10; 95% CI, 3.35-10.59; white dermographism: OR, 4.42; 95% CI, 1.68-11.64; Hertoghe sign: OR, 2.75; 95% CI, 1.27-5.93; nipple eczema: OR, 4.97; 95% CI, 1.56-15.78) was associated with increased probability of severe AD, while female sex was associated with reduced probability (OR, 0.30; 95% CI, 0.13-0.66). The probability of severe AD was associated with total serum immunoglobulin E levels greater than 1708 IU/mL and eosinophil values greater than 6.8%. Patients aged 12 to 21 years or older than 52 years had an elevated probability of severe AD; patients aged 22 to 51 years had an elevated probability of mild AD. Age at AD onset older than 12 years was associated with increased probability of severe AD up to a peak at 30 years; age at onset older than 33 years was associated with moderate to severe AD; and childhood onset was associated with mild AD (peak, 7 years). Lifestyle factors associated with severe AD were physical activity less than once per week and (former) smoking. Alopecia areata was associated with moderate (OR, 5.23; 95% CI, 1.53-17.88) and severe (OR, 4.67; 95% CI, 1.01-21.56) AD. Predictive performance of machine learning-gradient boosting vs multinomial logistic regression differed only slightly (mean multiclass area under the curve value: 0.71 [95% CI, 0.69-0.72] vs 0.68 [0.66-0.70], respectively). Conclusions and Relevance: The associations found in this cross-sectional study among patients with AD might contribute to a deeper disease understanding, closer monitoring of predisposed patients, and personalized prevention and therapy.
AU  - Maintz, L.*
AU  - Welchowski, T.*
AU  - Herrmann, N.*
AU  - Brauer, J.*
AU  - Kläschen, A.S.*
AU  - Fimmers, R.*
AU  - Schmid, M.*
AU  - Bieber, T.*
AU  - Schmid-Grendelmeier, P.*
AU  - Traidl-Hoffmann, C.
AU  - Akdis, C.*
AU  - Lauener, R.*
AU  - Brüggen, M.C.*
AU  - Rhyner, C.*
AU  - Bersuch, E.*
AU  - Renner, E.*
AU  - Reiger, M.
AU  - Dreher, A.*
AU  - Hammel, G.
AU  - Luschkova, D.
AU  - Lang, C.*
C1  - 64146
C2  - 51676
SP  - 1414-1424
TI  - Machine learning-based deep phenotyping of atopic dermatitis: Severity-associated factors in adolescent and adult patients.
JO  - JAMA Dermatol.
VL  - 157
IS  - 12
PY  - 2021
SN  - 2168-6084
ER  - 

TY  - JOUR
AB  - IMPORTANCE Differential diagnosis of congenital vascular anomalies is challenging, and misdiagnosis is frequent. Vascular malformations are considered one of the most difficult vascular diseases to treat. A new imaging approach that visualizes anatomical features and quantitatively assesses molecular biomarkers noninvasively would aid diagnosis and monitoring of treatment response of vascular malformations.OBJECTIVE To evaluate multispectral optoacoustic tomography (MSOT) for noninvasive assessment of molecular biomarkers for diagnosis and therapeutic monitoring of vascular malformations.DESIGN, SETTING, AND PARTICIPANTS This pilot study examined 6 patients with arteriovenous malformation (AVM) and 6 patients with venous malformation (VM) diagnosed according to the classification system of the International Society for the Study of Vascular Anomalies. All patients underwent clinical hybrid MSOT/ultrasonographic (US) imaging before and after treatment at an interdisciplinary vascular malformations clinic by trained MSOT and US examiners. Examiners were blinded to the patient history and stage of disease. Data were collected from April 11 to 25, 2017, and analyzed from May 1 to October 31, 2017.INTERVENTIONS Clinical hybrid MSOT/US imaging was performed before or within 1 week after endovascular embolization (for AVM) or percutaneous sclerotherapy (for VM).MAIN OUTCOMES AND MEASURES Region-of-interest analysis of the lesion and contralateral healthy tissue revealed quantitative values for oxygenated (HbO(2)) and deoxygenated (HbR) hemoglobin by spectral unmixing of optoacoustic data acquired at multiple wavelengths. The HbO(2):HbR ratio was calculated for healthy tissue and for AVM and VM before and after treatment.RESULTS Twelve patients (9 female and 3 male; mean [SD] age, 23 [18] years; age range, 6-59 years) with vascular malformations (6 with AVMs and 6 with VMs) were included. Significantly higher HbO(2):HbR ratios for AVMs (mean [SEM], 1.82 [0.08] vs 0.89 [0.03]; P < .001) and for VMs (mean [SEM], 1.12 [0.04] vs 0.89 [0.03]; P = .001) were found on MSOT tissue compared with healthy tissue. Significantly higher HbO(2):HbR ratios for AVMs compared with VMs (mean [SEM], 1.82 [0.08] vs 1.12 [0.04]; P < .001) were also found. Therefore, MSOT provided intrinsic biomarker patterns to distinguish both vascular malformations. After therapy, the HbO(2):HbR ratio dropped in correlation to treatment success validated by magnetic resonance imaging or angiography.CONCLUSIONS AND RELEVANCE This study suggests that different types of vascular malformations are clearly distinguished by MSOT-based, noninvasive assessment of hemoglobin levels in vascular malformations. The therapy effects found in this study could be instantly visualized, and this may offer a new tool for noninvasive diagnosis and monitoring of vascular malformations.
AU  - Masthoff, M.*
AU  - Helfen, A.*
AU  - Claussen, J.*
AU  - Karlas, A.
AU  - Markwardt, N.A.
AU  - Ntziachristos, V.
AU  - Eisenblätter, M.*
AU  - Wildgruber, M.*
C1  - 54466
C2  - 45607
CY  - 330 N Wabash Ave, Ste 39300, Chicago, Il 60611-5885 Usa
SP  - 1457-1462
TI  - Use of multispectral optoacoustic tomography to diagnose vascular malformations.
JO  - JAMA Dermatol.
VL  - 154
IS  - 12
PB  - Amer Medical Assoc
PY  - 2018
SN  - 2168-6084
ER  -