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Despite the abundance of data concerning biologic treatments for patients with psoriasis, clinicians are often challenged with discerning the optimal treatment for each patient. To inform this selection, this study explored whether a patient's baseline characteristics or disease profile could predict the likelihood of achieving complete skin clearance with biologic treatment. Machine-learning and other statistical methods were applied to the substantial data collected from patients with moderate-to-severe psoriasis in the ongoing, international, prospective, observational Psoriasis Study of Health Outcomes (PSoHO). The 3 measures of complete skin clearance were a psoriasis area and severity index (PASI)100 response at (a) week 12, (b) month 12, and (c) week 12 and maintain ed at month 6 and month 12 (PASI100 durability). From these real-world data, the absence of nail psoriasis emerged as the most consistent feature that may be used by clinicians to predict high-level treatment responses with biologic treatment. Other significant predictors of skin clearance with biologic treatments were the absence of hypertension and a lower body surface area affected by psoriasis. Overall, this study evidences the substantial challenge of identifying reliable clinical markers of treatment response for patients with psoriasis and highlights the importance of regular screening for psoriatic nail involvement.
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Productos Biológicos , Psoriasis , Índice de Severidad de la Enfermedad , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/diagnóstico , Masculino , Femenino , Productos Biológicos/uso terapéutico , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto , Factores de Tiempo , Aprendizaje Automático , Valor Predictivo de las Pruebas , Enfermedades de la Uña/tratamiento farmacológico , Inducción de Remisión , Piel/efectos de los fármacos , Piel/patología , Fármacos Dermatológicos/uso terapéuticoRESUMEN
BACKGROUND: Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. OBJECTIVES: To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. METHODS: Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. RESULTS: Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87-100%; NPV 68-100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92-100%; NPV 80-100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. CONCLUSIONS: Improvement in signs and symptoms early during treatment with baricitinib 4â mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.
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Dermatitis Atópica , Adulto , Humanos , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Prurito/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Resultado del Tratamiento , Estudios Clínicos como AsuntoRESUMEN
Nail psoriasis is a chronic, difficult-to-treat condition affecting almost half of patients with psoriasis. It is associated with considerable social stigma and impairment of patients' quality of life. The aim of this study was to assess improvements in objective measures of nail psoriasis among patients from the long-term extension of the UNCOVER-3 study who received the interleukin-17A inhibitor ixekizumab and had either any degree of nail psoriasis (Nail Psoriasis Severity Index (NAPSI) >=1) or significant nail psoriasis (fingernail NAPSI ≥ 16 and ≥ 4 fingernails involved) at baseline. Efficacy outcomes reported through week 264 included the mean percentage improvements from baseline in NAPSI score and the proportion of patients achieving nail psoriasis resolution (NAPSI=0). In UNCOVER-3, 56.9% (219/385) of patients had nail psoriasis at baseline; of those, 61.2% (134/219) had significant nail psoriasis. At week 60, a total of 66.9% and 59.1% of patients with baseline nail psoriasis and significant baseline nail psoriasis, respectively, reported complete clearance of nail psoriasis, an effect which was sustained through week 264. This analysis demonstrates that continuous treatment with ixekizumab in adult patients with moderate-to-severe-psoriasis through 264 weeks was associated with improvements and clearance of fingernail psoriasis, irrespective of the severity of nail psoriasis at baseline.
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Enfermedades de la Uña , Psoriasis , Adulto , Anticuerpos Monoclonales Humanizados , Método Doble Ciego , Humanos , Interleucina-17 , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/tratamiento farmacológico , Psoriasis/complicaciones , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Calidad de Vida , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In clinical practice, interruption of treatment may not result in immediate cessation of disease control, and some patients even experience sustained treatment response following treatment interruption. This post hoc analysis of UNCOVER-1 and -2 Phase 3 clinical trials characterized the time to loss of treatment response in patients with psoriasis who responded to ixekizumab through a 12-week treatment period, and who were then re-randomized to placebo for the following 48 weeks. For those with static Physician Global Assessment [sPGA]0/1 and Psoriasis Area and Severity Index [PASI]90 at Week 12, the median time to loss of PASI90 was 16.1 weeks (95% confidence interval 12.7-16.4). For those with PASI100 at Week 12, the median time to loss of PASI100 was 12.1 weeks (95% confidence interval 9.0-13.0). A small subset of patients maintained high levels of disease control through Week 60. This study adds to the growing body of evidence on sustained treatment response following treatment interruption.
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Fármacos Dermatológicos , Psoriasis , Anticuerpos Monoclonales Humanizados , Humanos , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice. OBJECTIVES: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response. RESULTS: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes. CONCLUSIONS: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.
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Artritis Psoriásica , Productos Biológicos , Psoriasis , Adulto , Productos Biológicos/uso terapéutico , Humanos , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Sulfonamidas , Resultado del TratamientoRESUMEN
BACKGROUND: Biologic drugs are generally recommended for treating moderate-to-severe psoriasis. While eligibility criteria are primarily defined by clinical treatment guidelines, access to these therapies varies between European countries and is regulated by country-specific reimbursement criteria. This post-hoc subgroup analysis of integrated data from two phase III trials (UNCOVER-2 and -3) reports the efficacy of ixekizumab relative to that of etanercept in patients with moderate-to-severe plaque psoriasis selected into groups defined by original reimbursement criteria from eight European countries. METHODS: This analysis included baseline and 12-week data from the ixekizumab- and etanercept-treated study populations from UNCOVER-2 and -3. Patients were classified as meeting/not meeting each country-specific biologic eligibility criterion. Efficacy was defined by Psoriasis Area and Severity Index (PASI) 75, 90, and 100 response rates and by Dermatology Life Quality Index (DLQI) (0,1) response rates. Treatment responses across subgroups were analysed using logistic regression models. RESULTS: PASI 75/90/100 response rates were significantly higher for ixekizumab-treated patients than for etanercept-treated patients at week 12 (P<0.05), irrespective of whether predefined reimbursement criteria were met, for all countries, with the exception of PASI 100 response in those meeting reimbursement criteria in Belgium, where sample size was very small. Clinical efficacy outcomes were corroborated by proportions of patients achieving DLQI (0,1) responses. CONCLUSIONS: The overall high efficacy of ixekizumab, and the consistency of the higher treatment effect compared with etanercept, in patients with moderate-to-severe psoriasis across a range of European biologic treatment reimbursement eligibility criteria provides new insights to inform treatment decisions in clinical practice. J Drugs Dermatol. 2022;21(6):659-667. doi:10.36849/JDD.6620.
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Productos Biológicos , Fármacos Dermatológicos , Psoriasis , Anticuerpos Monoclonales Humanizados , Productos Biológicos/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Fármacos Dermatológicos/uso terapéutico , Etanercept/uso terapéutico , Humanos , Psoriasis/inducido químicamente , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Psoriasis is a chronic inflammatory skin disorder that affects approximately 2-3% of the population worldwide and has severe effects on patients' physical and psychological well-being. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg(-1) groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg(-1) group and 13 out of 14 subjects in the 10 mg kg(-1) group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.
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Anticuerpos Monoclonales/uso terapéutico , Inmunoterapia , Interleucina-23/antagonistas & inhibidores , Terapia Molecular Dirigida , Psoriasis/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales Humanizados , Método Doble Ciego , Epitelio/efectos de los fármacos , Epitelio/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Interleucina-23/química , Interleucina-23/inmunología , Persona de Mediana Edad , Subunidades de Proteína/antagonistas & inhibidores , Subunidades de Proteína/química , Subunidades de Proteína/inmunología , Psoriasis/inmunología , Psoriasis/metabolismo , Psoriasis/patología , Piel/efectos de los fármacos , Piel/inmunología , Piel/metabolismo , Piel/patología , Resultado del Tratamiento , Adulto JovenRESUMEN
The Revised Illness Perception Questionnaire (IPQ-R) has been shown to assess illness perception reproducibly in primary cutaneous T-cell lymphomas (CTCL). Illness perception reflects patients' individual concepts of understanding and interpretation of the disease, influencing illness behaviour and health-related quality of life (HRQOL). This study investigated the clinical relevance of the relationships between illness perception, illness behaviour, and HRQOL in CTCL and cutaneous B-cell lymphomas (CBCL). A total of 92 patients completed the IPQ-R, the Scale for the Assessment of Illness Behavior (SAIB), and a skin-specific HRQOL tool (Skindex-29). Data on illness behaviour were not evidently related to illness perception, whereas illness perception was significantly associated with HRQOL. Both, IPQ-R and HRQOL results correlated with disease entity, stage, and socio-demographics. Only IPQ-R results provided practical information on patients' needs to train personal coping strategies. IPQ-R assessment in CTCL and CBCL might be a useful instrument to improve individual disease management.
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Conocimientos, Actitudes y Práctica en Salud , Conducta de Enfermedad , Linfoma de Células B/psicología , Linfoma Cutáneo de Células T/psicología , Pacientes/psicología , Percepción , Neoplasias Cutáneas/psicología , Adulto , Anciano , Costo de Enfermedad , Estudios Transversales , Femenino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células B/terapia , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/terapia , Encuestas y CuestionariosRESUMEN
This retrospective multicentre analysis from the Psoriasis Registry Austria (PsoRA) was conducted to determine drug effectiveness and survival of anti-tumour necrosis factor alpha (anti-TNF-α) agents in patients with moderate-to-severe chronic plaque psoriasis over a 9-year period. Data on 1,019 treatment cycles with adalimumab (n = 460), etanercept (n = 501), and/or infliximab (n = 58) administered to 827 patients (272 women, 555 men) were available for analysis. Compared with etanercept, adalimumab and infliximab showed superior short-term effectiveness. Intention-to-treat-calculated median drug survivals for adalimumab (1,264 days) and etanercept (1,438 days) were similar to each other (p = 0.74), but significantly superior to that of infliximab (477 days) (p = 7.0e-07 vs. adalimumab and p=2.2e-07 vs. etanercept, respectively). Their drug survival rates at 36 months were 51.6%, 56.0%, and 22.6%, respectively. Survival rates correlated significantly with effectiveness for adalimumab and etanercept, but not for infliximab.
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Actividades Cotidianas , Productos Biológicos/uso terapéutico , Inmunosupresores/uso terapéutico , Psoriasis/tratamiento farmacológico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Productos Biológicos/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Psoriasis/diagnóstico , Psoriasis/inmunología , Sistema de Registros , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/inmunología , Adulto JovenAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Artritis Psoriásica/complicaciones , Artritis Psoriásica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Tuberculosis Latente/complicaciones , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Humanos , Infección LatenteAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Fármacos Dermatológicos/efectos adversos , Farmacovigilancia , Psoriasis/tratamiento farmacológico , Infecciones Urinarias/epidemiología , Adulto , Anciano , Ensayos Clínicos como Asunto , Femenino , Humanos , Interleucina-17/antagonistas & inhibidores , Interleucina-17/inmunología , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/inmunología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Infecciones Urinarias/inducido químicamente , Infecciones Urinarias/inmunología , Adulto JovenRESUMEN
Mobile devices provide new opportunities to draw conclusions about cognitive performance in everyday situations. To gain insights into cognitive performance patterns in healthy adult populations, we adapted three established cognitive tests for smartphone use: the Digit Symbol Substitution Task (DSST), Sustained Attention to Response Task (SART), and Psychomotor Vigilance Task (PVT). To increase their feasibility for ambulatory assessment, we identified the minimum measurement durations that provide reliable and valid state measures of cognitive performance. Over 2 weeks, 46 participants performed each test once per day at random times, along with self-reports (e.g., on concentration, mood, and mental demands). The validity and reliability of change are promising for the 30-second PVT and 90-second DSST and SART. The DSST and SART provide fruitful outcomes for ambulatory field studies linked to mood, stress, and mental demands. We provide digital versions of the adapted DSST and SART online for free.
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Cognición , Psicometría , Teléfono Inteligente , Humanos , Masculino , Femenino , Adulto , Reproducibilidad de los Resultados , Adulto Joven , Pruebas Neuropsicológicas , Desempeño Psicomotor , Persona de Mediana Edad , Autoinforme , AtenciónRESUMEN
BACKGROUND: Nurses experience high job demands, which makes recovery particularly necessary to maintain well-being and performance. However, these demands also make recovery challenging. Short mindfulness meditations could potentially help alleviate this paradox. METHODS: Two ecological momentary intervention studies were conducted among geriatric nurses (Study 1: break study) and hospital nurses (Study 2: after-work study) to investigate whether short audio-guided mindfulness meditations are beneficial for recovery during breaks and psychological detachment after work. Furthermore, break recovery and after-work detachment were examined as mediators of the associations between mindfulness meditations and after-break/after-sleep mood and attention after respective recovery periods. Multilevel path models were based on a sample of 38 nurses and 208 after-break surveys in the break study and 26 nurses and 192 after-sleep surveys in the after-work study. RESULTS: Compared to breaks spent as usual, breaks that incorporated short mindfulness meditations were associated with higher break recovery, which mediated the positive associations between mindful breaks and after-break calmness, valence, and energetic arousal. Only with certain constraints did mindfulness meditations predict a lower rate of attention failures. In the after-work study, short mindfulness meditations were positively related to psychological detachment, which mediated the positive associations between the intervention and after-sleep valence and calmness. CONCLUSION/APPLICATION TO PRACTICE: Both pilot studies showed that short mindfulness meditations aid in recovery among nurses. However, to fully utilize the advantages of recovery-promoting breaks, structural changes are necessary to ensure that breaks of an appropriate duration are consistently implemented.
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INTRODUCTION: Nail psoriasis is highly prevalent among patients with psoriasis yet remains one of the most challenging areas to treat. To better understand the treatment landscape for psoriatic nail disease, more studies are needed that compare the effectiveness of different biologics for patients with nail psoriasis. This study contributes to this objective by directly comparing the effectiveness of approved biologics in improving nail psoriasis for patients up to month 12 in a real-world setting. METHODS: Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. This study assessed the change in modified Nail Psoriasis Severity Index (mNAPSI) score from baseline to months 3, 6 and 12 for 763 patients and compared the effectiveness of anti-interleukin (IL)-17A biologics versus other approved biologics, as well as ixekizumab versus secukinumab, guselkumab, risankizumab and adalimumab. Comparative adjusted analyses used frequentist model averaging (FMA). Least square mean difference (LSMD) in mNAPSI scores are presented as observed. RESULTS: Irrespective of the severity of nail psoriasis at baseline, the anti-IL-17A cohort had greater mean mNAPSI reductions from baseline compared to the other biologics cohort through month 12, reaching significance at months 3 and 6 in the adjusted analysis. For patients with moderate-to-severe nail psoriasis, ixekizumab showed numerically higher mean reductions in mNAPSI scores compared to all other studied biologics, reaching significance versus guselkumab at all timepoints and risankizumab at month 6. CONCLUSION: This real-world study showed that patients with moderate-to-severe psoriasis and any severity of concomitant nail involvement had significantly faster and more substantial improvements in nail psoriasis up to month 6 in the anti-IL-17A cohort compared to the other biologics cohort. Of the individual biologics studied, ixekizumab showed the highest numerical improvements in nail psoriasis at month 12. TRIAL REGISTRATION: EUPAS24207.
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The aim of this study is to investigate whether short, live-streaming activity and relaxation lunch breaks have positive associations with office workers' mood (calmness, valence, and energetic arousal), back pain, and attention after break and whether these associations are mediated by better break recovery. Additionally, we considered the two respite interventions as resources possibly buffering the effects of elevated situational job demands. Ten-minute break exercises were conducted during lunch breaks via Zoom live-stream, and data on those days were compared with data on days on which participants spent their breaks as usual. Our sample of 34 office workers provided data for 277 work days (209 in the home office and 68 on site at the company). Multilevel path models revealed positive total associations of both respite interventions with the mood dimension of calmness. Activity breaks additionally showed a positive association with the energetic arousal dimension of mood, while relaxation breaks were positively related to objectively measured cognitive performance. Interestingly, activity breaks moderated the relationships of job demands with calmness and valence, indicating their function as a stress-buffering resource. There were no significant associations between the two respite interventions and back pain. Supplemented by participants' feedback, the findings of this study suggest that offering short virtually guided break exercises may represent a feasible and office-compatible approach to promote break recovery, mood and functionality at work, especially regarding home-office work. Possible advantages and disadvantages of the live-streaming format are discussed.
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INTRODUCTION: Atopic dermatitis (AD) is a chronic, inflammatory skin disorder that impairs patients' quality of life (QoL). Physician assessment of AD disease severity is determined by clinical scales and assessment of affected body surface area (BSA), which might not mirror patients' perceived disease burden. METHODS: Using data from an international cross-sectional web-based survey of patients with AD and a machine learning approach, we sought to identify disease attributes with the highest impact on QoL for patients with AD. Adults with dermatologist-confirmed AD participated in the survey between July-September 2019. Eight machine learning models were applied to the data with dichotomised Dermatology Life Quality Index (DLQI) as the response variable to identify factors most predictive of AD-related QoL burden. Variables tested were demographics, affected BSA and affected body areas, flare characteristics, activity impairment, hospitalisation and AD therapies. Three machine learning models, logistic regression model, random forest and neural network, were selected on the basis of predictive performance. Each variable's contribution was computed via importance values from 0 to 100. For relevant predictive factors, further descriptive analyses were conducted to characterise those findings. RESULTS: In total, 2314 patients completed the survey with mean age 39.2 years (standard deviation 12.6) and average disease duration of 19 years. Measured by affected BSA, 13.3% of patients had moderate-to-severe disease. However, 44% of patients reported a DLQI > 10, indicative of a very large to extremely large impact on QoL. Activity impairment was the most important factor predicting high QoL burden (DLQI > 10) across models. Hospitalisation during the past year and flare type were also highly ranked. Current BSA involvement was not a strong predictor of AD-related QoL impairment. CONCLUSIONS: Activity impairment was the single most important factor for AD-related QoL impairment while current extent of AD did not predict higher disease burden. These results support the importance of considering patients' perspectives when determining the severity of AD.
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BACKGROUND: Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults. OBJECTIVES: To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements. METHODS: This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test. RESULTS: Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [p-value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [p = 0.001] and AD7: 2 mg = 40.4% [p = 0.087], 4 mg = 48.6% [p = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [p = 0.001] and AD7: 2 mg = 30.3% [p = 0.025], 4 mg = 34.2% [p = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL. CONCLUSION: Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity.
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Dermatitis Atópica , Inhibidores de las Cinasas Janus , Humanos , Adulto , Dermatitis Atópica/tratamiento farmacológico , Calidad de Vida , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Sulfonamidas/efectos adversos , Resultado del Tratamiento , Inhibidores de las Cinasas Janus/uso terapéutico , Método Doble CiegoRESUMEN
INTRODUCTION: Limited data exist on skin cancer risk in patients with psoriasis using biologics. Here, we report treatment-emergent adverse events (TEAEs) of skin cancer in patients treated with ixekizumab from psoriasis clinical trials. METHODS: Integrated safety databases from 17 clinical trials of adults with moderate-to-severe psoriasis treated with ≥ 1 dose of ixekizumab for ≤ 5 years were used to analyze exposure-adjusted incidence rates (IRs) per 100 patient-years of exposure (PYE) and clinically characterize dermatologist-adjudicated skin cancer TEAEs. RESULTS: Of 6892 patients, 58 presented with ≥ 1 skin cancer TEAE (IR 0.3) with IRs remaining stable with longer ixekizumab exposure. Non-melanoma skin cancer (NMSC) was the most common event (IR 0.3) affecting 55 patients; of those, 44 had basal cell carcinoma (IR 0.2) and 16 had squamous cell carcinoma (IR 0.1). Two treatment-emergent melanoma events were identified; neither were classified as serious AEs. CONCLUSIONS: Incidence of skin neoplasms in patients with psoriasis treated with ixekizumab for ≤ 5 years was low, and among those events, NMSC was most common. Limitations included that longer exposure may be required to confirm risk of skin cancer and that the study exclusion criteria of several studies, which excluded patients with skin cancer events within 5 years prior to baseline, might limit interpretation of skin cancer risk in this cohort. These findings support the safety profile of ixekizumab for patients requiring long-term psoriasis control.
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Introduction: Psoriasis localized at the scalp, face, nails, genitalia, palms, and soles can exacerbate the disease burden. Real-world studies comparing the effectiveness of treatments for these special areas are limited. Methods: Psoriasis Study of Health Outcomes (PSoHO) is an international, prospective, non-interventional, study comparing the effectiveness of anti-interleukin (IL)-17A biologics (ixekizumab and secukinumab) compared to other approved biologics and the pairwise comparative effectiveness of ixekizumab relative to five other individual biologics for patients with moderate-to-severe psoriasis. To determine special area involvement, physicians answered binary questions at baseline and week 12. The proportion of patients who achieved special area clearance at week 12 was assessed. Missing outcome data were imputed as non-response. Comparative treatment analyses were conducted using frequentist model averaging. Results: Of the 1,978 patients included, 83.4% had at least one special area involved at baseline with the scalp (66.7%) as the most frequently affected part, followed by nails (37.9%), face/neck (36.9%), genitalia (25.6%), and palms and/or soles (22.2%). Patients with scalp, nail, or genital, but not palmoplantar or face/neck psoriasis, had significantly higher odds of achieving clearance at week 12 in the anti-IL-17A cohort compared to the other biologics cohort. Patients with scalp psoriasis had a 10-20% higher response rate and significantly greater odds (1.8-2.3) of achieving clearance at week 12 with ixekizumab compared to included biologics. Conclusion: Biologics demonstrate a high level of clearance of special areas at week 12 in a real-world setting. Patients with scalp, nail, or genital involvement have significantly higher odds of clearance at week 12 with anti-IL-17A biologics compared to other biologics.
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INTRODUCTION: We explored patient satisfaction with baricitinib, an oral Janus kinase inhibitor, in patients with atopic dermatitis (AD) treated in routine clinical practice. METHODS: Adults with moderate-to-severe AD treated with baricitinib in clinical practice for ≥4 weeks in France, Germany, and the UK completed a one-time online survey under market research methodologies. Treatment satisfaction was assessed using a Likert scale and abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9). Patients reported demographic, disease, and treatment information. Data were analyzed descriptively. RESULTS: The survey was completed by 170 patients with a mean age of 39.3 years (SD = 13.5), 59% (n = 101) were female. At baricitinib initiation, 79% rated their AD as "Severe", yet 28% reported body surface area (BSA) involvement ≥10%. Most were "Satisfied" or "Very satisfied" (76%/18%) with baricitinib, with high rates reported for controlling itch (36%/56%). Itch improvements were noted by 97% of patients. Some tapered/stopped (50%/32%) topical corticosteroid use, aligned with reported improvements on the patient global assessment and BSA. Mean TSQM-9 convenience score was 78.0 (SD = 14.0). CONCLUSIONS: Satisfaction with itch control was particularly high, reflected in rates of improvement in itch since starting baricitinib. On the TSQM-9, the convenience score was the highest. Many patients tapered/stopped concomitant topicals, indicating baricitinib's effect in controlling AD symptoms.