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1.
Dermatol Ther (Heidelb) ; 14(5): 1127-1144, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38696027

RESUMO

INTRODUCTION: Atopic dermatitis (AD) is characterized by intense itch and other symptoms that negatively impact quality of life (QoL). This study evaluates the effect of upadacitinib (an oral selective Janus kinase inhibitor) monotherapy on patient-reported outcomes (PROs) among adults and adolescents with moderate-to-severe AD over 16 weeks. METHODS: This integrated analysis of the double-blind, placebo-controlled periods of phase 3 monotherapy clinical trials Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) assessed itch (Worst Pruritus Numerical Rating Scale [WP-NRS] and SCORing Atopic Dermatitis [SCORAD]), skin pain and symptom severity (AD Symptom Scale), symptom frequency (Patient-Oriented Eczema Measure), sleep (AD Impact Scale [ADerm-IS] and SCORAD), daily activities and emotional state (ADerm-IS), QoL (Dermatology Life Quality Index [DLQI] and Children's DLQI), mental health (Hospital Anxiety and Depression Scale), and patient impressions (Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment). RESULTS: Data from 1683 patients (upadacitinib 15 mg, n = 557; upadacitinib 30 mg, n = 567; placebo, n = 559) were analyzed. A greater proportion of patients receiving upadacitinib versus placebo experienced improvements in itch (≥ 4-point improvement on WP-NRS) by week 1 (upadacitinib 15 mg, 11.2%; upadacitinib 30 mg, 17.7%; placebo, 0.5%; P < 0.001), with response rates sustained through week 16 (upadacitinib 15 mg, 47.1%; upadacitinib 30 mg, 59.8%; placebo, 10.4%; P < 0.001). Improvements were similar for PROs assessing skin pain/symptoms, sleep, daily activities, QoL, emotional state, mental health, and patient impressions of disease severity and treatment. Responses generally improved rapidly (within 1-2 weeks), increased through weeks 4-6, and were maintained through week 16. CONCLUSIONS: Once-daily oral upadacitinib monotherapy improved response rates across PROs compared with placebo. Upadacitinib therapy resulted in rapid, sustained improvements in PROs measuring symptom burden and QoL in adults and adolescents with moderate-to-severe AD. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03569293 and NCT03607422.


Atopic dermatitis, or eczema, is characterized by itchy, dry, inflamed skin. These symptoms often make it difficult for patients to get adequate sleep. Patients with atopic dermatitis may also experience anxiety, depression, reduced self-confidence, social isolation, disruption to daily activities like school and work, and decreased quality of life. Many atopic dermatitis symptoms, including itch and psychological impact, are difficult for doctors to assess. Thus, it is important to consider patients' descriptions of their symptoms and quality of life, particularly when assessing treatment benefit. Upadacitinib is an orally administered drug approved to treat moderate-to-severe atopic dermatitis. We investigated how upadacitinib (15 mg or 30 mg) given once daily to adults and adolescents with moderate-to-severe atopic dermatitis in the Measure Up 1 and 2 clinical trials impacts their symptoms and quality of life over a 16-week period. We compared changes in patient-reported itch, pain, sleep, daily activities, emotional state, mental health, and overall quality of life among patients in the clinical trials who received upadacitinib with those in the same studies who received a dummy (placebo) treatment. Upadacitinib improved patient-reported symptoms and quality of life early in the clinical trials, often within the first 1­2 weeks. The extent of the improvements increased through weeks 4­6 of treatment and lasted through week 16. Patients who received upadacitinib reported greater improvements in symptoms and quality of life than did patients who received placebo. Upadacitinib treatment resulted in rapid and lasting improvements in the well-being of patients with atopic dermatitis.

2.
J Dermatolog Treat ; 34(1): 2222201, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37349865

RESUMO

BACKGROUND: Patients with moderate-to-severe atopic dermatitis (AD) experience skin lesions and intense itch that substantially affect quality of life. Patients have choices among systemic AD treatments that offer varied benefit-risk profiles. OBJECTIVE: Measure patients' willingness to trade off the risks and benefits of systemic treatments among individuals with a physician-confirmed diagnosis of moderate-to-severe AD. METHODS: Patients participated in a discrete choice experiment online survey with a series of choices between hypothetical AD treatments defined by six attributes reflecting benefits and risks of treatments (itch reduction, time until noticeable itch reduction, chance of clear or almost clear skin, risk of serious infection, risk of developing acne, and need for prescription topical steroids). Data were analyzed with a random parameters logit model to quantify preferences and the relative importance of attributes for treatment alternatives. RESULTS: Respondents (n = 200) placed the highest relative importance on itch reduction, speed of itch reduction, and skin clearance, and were generally willing to accept clinically relevant levels of risk of serious infection and acne in exchange for treatment benefits. CONCLUSIONS: Patients with moderate-to-severe AD were willing to trade clinically relevant treatment risks for greater or more rapid itch reduction and skin clearance offered by systemic therapies.


Assuntos
Acne Vulgar , Dermatite Atópica , Humanos , Dermatite Atópica/tratamento farmacológico , Preferência do Paciente , Qualidade de Vida , Pele , Acne Vulgar/tratamento farmacológico
3.
J Am Acad Dermatol ; 89(3): 478-485, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37230366

RESUMO

BACKGROUND: Characterization of upadacitinib use and switching from dupilumab to upadacitinib among patients with moderate-to-severe atopic dermatitis (AD) is needed. OBJECTIVE: To evaluate the long-term safety and efficacy of continuous upadacitinib 30 mg and switching to upadacitinib after 24 weeks of dupilumab. METHODS: Adults who completed the phase 3b clinical trial of oral upadacitinib 30 mg vs injectable dupilumab 300 mg (Heads Up) and entered a 52-week open-label extension (OLE) (NCT04195698) were included. All patients received 30-mg upadacitinib during the open-label period. We report results of a prespecified interim OLE 16-week analysis. RESULTS: Patients (n = 239) continuing upadacitinib maintained high levels of skin and itch response. Patients (n = 245) switching from dupilumab experienced additional incremental improvements in clinical responses within 4 weeks of starting upadacitinib. Most patients who did not achieve adequate clinical responses with dupilumab did so with upadacitinib. The safety profile of upadacitinib up to 40 weeks (week 16 of OLE) was consistent with previous phase 3 AD studies, with no new safety risks observed. LIMITATIONS: Open-label study design. CONCLUSIONS: Clinical responses are maintained with continuous upadacitinib through 40 weeks and patients regardless of prior dupilumab response experienced improved outcomes when switched to upadacitinib. No new safety risks were observed.


Assuntos
Dermatite Atópica , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Resultado do Tratamento , Método Duplo-Cego , Índice de Gravidade de Doença
4.
JAMA Dermatol ; 159(5): 526-535, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37043227

RESUMO

Importance: Atopic dermatitis onset usually occurs in childhood. Persistence of disease into adolescence and adulthood is common. It is important to evaluate new treatment options in adolescents because of the high unmet need in this population. Objective: To assess the efficacy and safety of upadacitinib to treat moderate-to-severe atopic dermatitis in adolescents. Design, Setting, and Participants: Prespecified analysis of adolescents enrolled in 3 randomized, double-blind, placebo-controlled phase 3 clinical trials in more than 20 countries across Europe, North and South America, Oceania, the Middle East, and the Asia-Pacific region from July 2018 through December 2020. Participants were adolescents aged 12 to 17 years with moderate-to-severe atopic dermatitis. Data analysis was performed from April to August 2021. Interventions: Patients were randomized (1:1:1) to once-daily oral upadacitinib 15 mg, upadacitinib 30 mg, or placebo alone (Measure Up 1 and Measure Up 2) or with topical corticosteroids (AD Up). Main Outcomes and Measures: Safety and efficacy, including at least a 75% improvement in the Eczema Area and Severity Index from baseline and validated Investigator Global Assessment for Atopic Dermatitis score of 0 (clear) or 1 (almost clear) at week 16 (coprimary end points). Results: A total of 552 adolescents (290 female; 262 male) were randomized. Mean (SD) age was 15.4 (1.8), 15.5 (1.7), and 15.3 (1.8) years for adolescents in Measure Up 1, Measure Up 2, and AD Up, respectively. In Measure Up 1, Measure Up 2, and AD Up, respectively, a greater proportion of adolescents (% [95% CI]) achieved at least 75% improvement in the Eczema Area and Severity Index at week 16 with upadacitinib 15 mg (73% [63%-84%], 69% [57%-81%], 63% [51%-76%]), and upadacitinib 30 mg (78% [68%-88%], 73% [62%-85%], 84% [75%-94%]), than with placebo (12% [4%-20%], 13% [5%-22%], 30% [19%-42%]; nominal P < .001 for all comparisons vs placebo). Similarly, a greater proportion of adolescents treated with upadacitinib achieved a validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1 at week 16 and improvements in quality of life with upadacitinib than with placebo. Upadacitinib was generally well tolerated in adolescents. Acne was the most common adverse event, and all acne events were mild or moderate. Conclusions and Relevance: In this analysis of 3 randomized clinical trials, upadacitinib was an effective treatment for adolescents with moderate-to-severe atopic dermatitis, with an acceptable safety profile. Trial Registration: ClinicalTrials.gov Identifiers: NCT03569293 (Measure Up 1), NCT03607422 (Measure Up 2), and NCT03568318 (AD Up).


Assuntos
Dermatite Atópica , Eczema , Adolescente , Feminino , Humanos , Masculino , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento
5.
J Allergy Clin Immunol ; 151(1): 172-181, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36195170

RESUMO

BACKGROUND: Upadacitinib is a selective reversible Janus kinase (JAK) inhibitor with established efficacy in moderate-to-severe atopic dermatitis (AD). OBJECTIVE: We evaluated the safety of upadacitinib in patients with moderate-to-severe AD. METHODS: Integrated safety data from the 16-week placebo-controlled periods of 1 phase 2b and 3 ongoing phase 3 studies (16 weeks) and longer-term safety data from patients receiving upadacitinib during the blinded extension periods of the three phase 3 studies were analyzed (all upadacitinib exposure). Treatment-emergent adverse events (TEAEs) were presented as exposure-adjusted rates per 100 patient-years (PY). RESULTS: Safety results were similar between the 16-week and all upadacitinib exposure groups. The latter group included 2485 patients (333 adolescents), receiving upadacitinib 15 mg (n = 1239) or 30 mg (n = 1246) for a mean duration of approximately 1 year. Upadacitinib was well tolerated by both adults and adolescents. TEAEs and discontinuation due to AEs were reported more frequently in patients receiving 30 mg upadacitinib (respectively, 311.9 and 5.7 events per 100 PY) versus 15 mg (respectively, 274.6 and 4.4 events per 100 PY). Serious adverse event rates (15/30 mg, 7.1/7.7 events per 100 PY) were similar in both groups. Acne was the most frequently reported adverse event (15/30 mg, 13.3/20.2 events per 100 PY). Serious infection rates were similar across treatment groups. Adjudicated major adverse cardiovascular event and venous thromboembolic event rates were ≤0.1 events per 100 PY. Rates of malignant neoplasms were within the expected range for the general population. CONCLUSIONS: Upadacitinib was well tolerated, and no new important safety risks were observed among adults and adolescents with moderate-to-severe AD treated for approximately 1 year compared to the known safety profile of upadacitinib.


Assuntos
Dermatite Atópica , Compostos Heterocíclicos com 3 Anéis , Inibidores de Janus Quinases , Adolescente , Adulto , Humanos , Dermatite Atópica/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Inibidores de Janus Quinases/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento
6.
J Am Acad Dermatol ; 87(4): 784-791, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35714786

RESUMO

BACKGROUND: Acne is the most frequent adverse event associated with upadacitinib treatment in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: To characterize the adverse event of acne associated with upadacitinib. METHODS: This was a post hoc integrated analysis of 3 phase 3 randomized, double-blind, placebo-controlled trials of upadacitinib, alone (NCT03569293 and NCT03607422) or in combination with topical corticosteroids (NCT03568318). Data included were from the 16-week placebo-controlled period. RESULTS: Over 16 weeks, 84 of 857 (9.8%), 131 of 864 (15.2%), and 19 of 862 (2.2%) patients randomized to receive upadacitinib 15 mg, upadacitinib 30 mg, and placebo, respectively, experienced acne. All cases of acne, except 1, were mild/moderate in severity; 2 patients discontinued treatment due to moderate acne. Acne occurred at higher rates among younger, female, and non-White patients. Acne required no intervention in 40.5% and 46.6% of patients receiving upadacitinib 15 and 30 mg, respectively; most remaining cases were managed with topical antibiotics, benzoyl peroxide, and/or retinoids. Acne also had no impact on patient-reported outcomes. LIMITATIONS: This study was relatively short in duration and had a small patient population. CONCLUSIONS: Acne associated with upadacitinib for atopic dermatitis treatment is usually mild/moderate in severity and managed with topical therapies or no intervention.


Assuntos
Acne Vulgar , Dermatite Atópica , Acne Vulgar/induzido quimicamente , Acne Vulgar/tratamento farmacológico , Corticosteroides/uso terapêutico , Antibacterianos/uso terapêutico , Peróxido de Benzoíla/uso terapêutico , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis , Humanos , Retinoides/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento
7.
Dermatitis ; 33(6S): S24-S36, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35318974

RESUMO

ABSTRACT: Atopic dermatitis (AD) is a common, chronic, inflammatory skin condition that affects people of all ages, races, and ethnicities. The condition is heterogeneous in both clinical presentation (phenotype) and underlying pathobiology (endotype). Atopic dermatitis diagnosis, assessment, and monitoring rely on clinical evaluation because there are no definitive biomarkers for AD. This review addresses variation in the clinical presentation of AD across the spectrum of Fitzpatrick skin types, with an emphasis on clinical evaluation challenges in patients with skin of color. We present photographs from phase 3 clinical trials that evaluated the safety and efficacy of upadacitinib among patients with moderate-to-severe AD and demonstrate the challenges in evaluating the clinical signs of AD (erythema and excoriation in patients with dark skin types and lichenification in those with light skin types) by illustrating the changes in clinical signs and symptoms that can be achieved with targeted systemic therapies.


Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Pele
8.
J Allergy Clin Immunol ; 149(3): 977-987.e14, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34403658

RESUMO

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.


Assuntos
Corticosteroides/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Administração Tópica , Adolescente , Corticosteroides/efeitos adversos , Adulto , Idoso , Criança , Dermatite Atópica/patologia , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
9.
JAMA Dermatol ; 157(9): 1047-1055, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34347860

RESUMO

IMPORTANCE: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement. OBJECTIVE: To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD. DESIGN, SETTING, AND PARTICIPANTS: Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population. INTERVENTIONS: Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week. MAIN OUTCOMES AND MEASURES: The primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug. RESULTS: Of 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab. CONCLUSIONS AND RELEVANCE: During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dupilumab in patients with moderate-to-severe AD, with no new safety signals. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03738397.


Assuntos
Dermatite Atópica , Eczema , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Lancet ; 397(10290): 2169-2181, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34023009

RESUMO

BACKGROUND: Systemic therapies are typically combined with topical corticosteroids for the management of moderate-to-severe atopic dermatitis. Upadacitinib is an oral Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2 that is being tested for atopic dermatitis. We aimed to assess the efficacy and safety of upadacitinib plus topical corticosteroids compared with placebo for the treatment of moderate-to-severe atopic dermatitis. METHODS: In this randomised, double-blind, placebo-controlled, phase 3 trial (AD Up) adults (aged 18-75 years) and adolescents (aged 12-17 years) with chronic atopic dermatitis that was moderate to severe (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] score of ≥16, validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] score of ≥3, and weekly average Worst Pruritus Numerical Rating Scale score of ≥4 at baseline) were enrolled at 171 clinical centres across 22 countries in the Asia-Pacific region, Europe, the Middle East, North America, and Oceania. Patients were randomly assigned (1:1:1) to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo once daily, all in combination with topical corticosteroids for 16 weeks. Randomisation was done using an interactive response technology system, stratified by baseline disease severity, geographical region, and age. Study investigators, study site personnel, and patients were masked to study treatment. The coprimary endpoints were the proportion of patients who had achieved at least a 75% reduction in EASI score from baseline (EASI-75) and the proportion of patients who had achieved a vIGA-AD response (defined as a vIGA-AD score of 0 [clear] or 1 [almost clear] with ≥2 grades of improvement from baseline) at week 16. Efficacy was analysed in the intention-to-treat population and safety was analysed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03568318, and is active, but not recruiting. FINDINGS: Between Aug 9, 2018, and Dec 20, 2019, 901 patients were randomly assigned to receive upadacitinib 15 mg plus topical corticosteroids (n=300), upadacitinib 30 mg plus topical corticosteroids (n=297), or placebo plus topical corticosteroids (n=304). At week 16, the proportion of patients who had achieved EASI-75 was significantly higher in the upadacitinib 15 mg plus topical corticosteroid group (194 [65%] of 300 patients) and the upadacitinib 30 mg plus topical corticosteroids group (229 [77%] of 297 patients) than the placebo group (80 [26%] of 304 patients; adjusted difference in EASI-75 response rate vs placebo, 38·1% [95% CI 30·8-45·4] for the upadacitinib 15 mg group and 50·6% [43·8-57·4] for the upadacitinib 30 mg group; p<0·0001 for both doses). The proportion of patients who had achieved a vIGA-AD response at week 16 was significantly higher in the upadacitinib 15 mg plus topical corticosteroid group (119 [40%] patients) and upadacitinib 30 mg plus topical corticosteroid group (174 [59%] patients) than the placebo group (33 [11%] patients; adjusted difference in vIGA-AD response vs placebo, 28·5% [22·1-34·9] for the upadacitinib 15 mg group and 47·6% [41·1-54·0] for the upadacitinib 30 mg group; p<0·0001 for both doses). During the double-blind period, upadacitinib 15 and 30 mg were well tolerated in combination with topical corticosteroids. The most frequently reported treatment-emergent adverse events (≥5% in any treatment group) were acne, nasopharyngitis, upper respiratory tract infection, oral herpes, elevation of blood creatine phosphokinase levels, headache, and atopic dermatitis. The incidence of acne was higher in the upadacitinib 15 mg (30 [10%] of 300 patients) and upadacitinib 30 mg (41 [14%] of 297 patients) groups than the placebo group (six [2%] of 304 patients). The incidence of adverse events leading to discontinuation of study drug (four [1%] patients in the upadacitinib 15 mg plus topical corticosteroids group, four [1%] patients in the upadacitinib 30 mg plus topical corticosteroids group, and seven [2%] patients in the placebo plus topical corticosteroids group) and serious adverse events (seven [2%] patients, four [1%] patients, and nine [3%] patients) were similar among treatment groups. No deaths were reported in any treatment group. INTERPRETATION: Upadacitinib plus topical corticosteroids was well tolerated and superior to placebo plus topical corticosteroids. Upadacitinib as combination therapy had a positive benefit-risk profile in adults and adolescents with moderate-to-severe atopic dermatitis. FUNDING: AbbVie.


Assuntos
Corticosteroides/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Quimioterapia Combinada , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Índice de Gravidade de Doença , Adulto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Humanos , Internacionalidade , Janus Quinase 1 , Inibidores de Janus Quinases/administração & dosagem , Masculino
15.
18.
Clin Dermatol ; 35(4): 344-348, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28709563

RESUMO

Fred Wise (1881-1950) and Marion Sulzberger (1895-1983) are often credited with introducing the term atopic dermatitis to dermatology in 1933. This definition was based on atopy, a term first created by Arthur Coca (1875-1959) and Robert Cooke (1880-1960) in 1923, when they recognized an association between allergic rhinitis and asthma. Despite its recent introduction into our medical lexicon, historical precursors of atopic dermatitis date back to at least as early as 69-140 ce. In this contribution, we highlight both the prominent individuals credited with shaping the disorder into our current interpretation and the suspected historical precursors of this disease and reported treatments.


Assuntos
Dermatite Atópica/história , Asma/história , Dermatologia/história , História do Século XVI , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , História Antiga , Humanos , Rinite Alérgica/história
19.
Adv Skin Wound Care ; 29(6): 278-86, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27171256

RESUMO

PURPOSE: To provide information from a literature review about the prevention, recognition, and treatment for contact dermatitis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES: After participating in this educational activity, the participant should be better able to:1. Identify signs and symptoms of and diagnostic measures for contact dermatitis.2. Identify causes and risks for contact dermatitis.3. Select appropriate treatment for contact dermatitis and its prevention. ABSTRACT: Contact dermatitis to wound care products is a common, often neglected problem. A review was conducted to identify articles relevant to contact dermatitis.A PubMed English-language literature review was conducted for appropriate articles published between January 2000 and December 2015.Contact dermatitis is both irritant (80% of cases) or allergic (20% of cases). Frequent use of potential contact allergens and impaired barrier function of the skin can lead to rising sensitization in patients with chronic wounds. Common known allergens to avoid in wound care patients include fragrances, colophony, lanolin, and topical antibiotics.Clinicians should be cognizant of the allergens in wound care products and the potential for sensitization. All medical devices, including wound dressings, adhesives, and bandages, should be labeled with their complete ingredients, and manufacturers should be encouraged to remove common allergens from wound care products, including topical creams, ointments, and dressings.


Assuntos
Dermatite Alérgica de Contato/etiologia , Dermatite Irritante/etiologia , Fármacos Dermatológicos/efeitos adversos , Ferimentos e Lesões/tratamento farmacológico , Alérgenos/efeitos adversos , Dermatite Alérgica de Contato/fisiopatologia , Dermatite Alérgica de Contato/terapia , Dermatite Irritante/fisiopatologia , Dermatite Irritante/terapia , Fármacos Dermatológicos/uso terapêutico , Educação Médica Continuada , Feminino , Seguimentos , Humanos , Masculino , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Índice de Gravidade de Doença , Higiene da Pele/efeitos adversos , Higiene da Pele/métodos , Testes Cutâneos , Resultado do Tratamento , Técnicas de Fechamento de Ferimentos/efeitos adversos , Ferimentos e Lesões/diagnóstico
20.
J Am Acad Dermatol ; 73(6): 929-44; quiz 945-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26568337

RESUMO

In the 21st century, despite increased globalization through international travel for business, medical volunteerism, pleasure, and immigration/refugees into the United States, there is little published in the dermatology literature regarding the cutaneous manifestations of helminth infections. Approximately 17% of travelers seek medical care because of cutaneous disorders, many related to infectious etiologies. This review will focus on the cutaneous manifestations of helminth infections and is divided into 2 parts: part I focuses on nematode infections, and part II focuses on trematode and cestode infections. This review highlights the clinical manifestations, transmission, diagnosis, and treatment of helminth infections. Nematodes are roundworms that cause diseases with cutaneous manifestations, such as cutaneous larval migrans, onchocerciasis, filariasis, gnathostomiasis, loiasis, dracunculiasis, strongyloidiasis, ascariasis, streptocerciasis, dirofilariasis, and trichinosis. Tremadotes, also known as flukes, cause schistosomiasis, paragonimiasis, and fascioliasis. Cestodes (tapeworms) are flat, hermaphroditic parasites that cause diseases such as sparganosis, cysticercosis, and echinococcus.


Assuntos
Antinematódeos/uso terapêutico , Nematoides/isolamento & purificação , Infecções por Nematoides/diagnóstico , Infecções por Nematoides/epidemiologia , Dermatopatias Parasitárias/diagnóstico , Dermatopatias Parasitárias/epidemiologia , Animais , Biópsia por Agulha , Progressão da Doença , Doenças Endêmicas , Feminino , Helmintíase/diagnóstico , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintos/isolamento & purificação , Humanos , Imuno-Histoquímica , Incidência , Masculino , Infecções por Nematoides/tratamento farmacológico , Prognóstico , Medição de Risco , Dermatopatias Parasitárias/terapia , Resultado do Tratamento , Clima Tropical
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