RESUMO
BACKGROUND: Treatment optimization may require dosing flexibility. The Phase 3 JADE REGIMEN trial (NCT03627767) evaluated maintenance of abrocitinib 200 mg-induced response in patients with moderate-to-severe atopic dermatitis (AD) randomly assigned to subsequent maintenance with continuous-dose abrocitinib (200 mg), reduced-dose abrocitinib (100 mg) or placebo. Maintenance with continuous-dose abrocitinib was associated with a stronger prevention of disease flares, but also with a higher occurrence of adverse events, compared with the reduced dose. OBJECTIVE: This post hoc analysis of JADE REGIMEN aimed to identify predictors of not flaring during the maintenance period and to generate tools that can be used to assess probability of not flaring. METHODS: Data were analysed from patients who responded to abrocitinib 200 mg induction therapy (12 weeks) and were randomly assigned to receive abrocitinib (200 mg or 100 mg) or placebo in the 40-week maintenance period. Demographic and baseline disease characteristics and level of response to induction were evaluated for association with not flaring using logistic regression. Parameters with a significant (p < 0.15) interaction with the treatment arm were fitted into a multivariable regression model, which was used to assess probability of not flaring. RESULTS: Lower percentage body surface area affected at baseline (p = 0.09), absence of prior exposure to systemic agents (p = 0.02) and greater percentage change in EASI from baseline to randomization (p < 0.001) were identified as predictors of not flaring with abrocitinib. In both abrocitinib arms, percentage change in EASI from baseline to end of induction (Week 12) was the major contributor to the probability of not flaring in the maintenance period. CONCLUSIONS: Maintenance of response using reduced-dose abrocitinib 100 mg may be feasible for patients with lower baseline disease severity and strong response to abrocitinib 200 mg induction treatment.
RESUMO
BACKGROUND: It is not fully understood how different degrees of improvements in atopic dermatitis (AD) clinical outcome measures translate to improvements in patient-reported outcome (PRO) measures, such as those assessing itch, symptoms, sleep, anxiety, depression, quality of life (QoL), and work productivity. OBJECTIVES: This post hoc analysis of three clinical studies assessed how more robust improvements in clinical responses are associated with improvements in PROs and QoL. METHODS: Data from three randomized, double-blind, placebo-controlled, phase 3 trials in adults and adolescents with moderate to severe atopic dermatitis (Measure Up 1, Measure Up 2, and AD Up) were included. Patients were randomly assigned (1:1:1) to upadacitinib (15 or 30 mg) or placebo once daily (alone or in combination with topical corticosteroids). The mean percentage improvement from baseline to week 16 and percentage of patients achieving responses at week 16 were summarized by the Eczema Area and Severity Index (EASI) and validated Investigator Global Assessment of Atopic Dermatitis (vIGA-AD) response level categories. RESULTS: A total of 2392 patients from the three trials were included in the analysis. Increasingly greater mean percentage improvement and proportion of patients achieving response was observed at higher clinical response levels (i.e., stepwise pattern). Mean percentage improvement and proportion of patients achieving response exceeded 69% and 70% at EASI ≥ 90 and vIGA-AD 0/1, respectively, for most PROs including Worst Pruritus Numeric Rating Scale, Patient Oriented Eczema Measure, and Dermatology Life Quality Index. CONCLUSIONS: Greater degrees of clinical responses are related to more robust improvements across multiple dimensions impacted by AD, including itch, skin pain, sleep, anxiety, depression, and QoL.
RESUMO
Despite the emergence of novel targeted treatments for atopic dermatitis (AD), there is a lack of guidelines on standardizing analysis of clinical trial data. To define and estimate meaningful treatment comparisons, several factors, including intercurrent events, must be taken into account. Intercurrent events are defined as events occurring after treatment initiation that affect either the interpretation or existence of the measurements associated with clinical questions of interest. Due to the relapsing, unpredictable nature of AD, intercurrent events frequently occur in AD trials, such as use of rescue therapy for intense itch and sleep deprivation. Despite the impact of intercurrent events in AD, they are often handled in an inconsistent manner across trials, which limits results interpretation. The estimand framework is increasingly used to estimate treatment effects while accounting for intercurrent events. This review explores how guidance from the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) on the use of estimands can be applied to support AD clinical trial design and analysis. We propose that estimands are used in AD trials and defined early during trial design. The use of estimands can provide clinicians with interventional trial results that are more reflective of clinical practice, help facilitate comparisons across clinical trials, and are more informative to enable improved treatment selection for patients.
Assuntos
Dermatite Atópica , Modelos Estatísticos , Humanos , Dermatite Atópica/tratamento farmacológico , Prova Pericial , Interpretação Estatística de Dados , Projetos de PesquisaRESUMO
Atopic dermatitis (AD) and food allergy (FA) share similar type 2 inflammation and commonly co-occur, but the precise proportion of AD patients with FA and vice versa, as well as the effect of AD disease severity on the strength of this association remains uncertain. The aim of this comprehensive systematic review and meta-analysis was to determine the prevalence and bidirectional associations of AD with food sensitivity (FS), FA and challenge-proven food allergy (CPFA). We searched PubMed and EMBASE and three independent reviewers performed title/abstract and full-text review and data extraction. Overall, 557 articles (n = 225,568 individuals with AD, n = 1,128,322 reference individuals; n = 1,357,793 individuals with FS, FA or CPFA, n = 1,244,596 reference individuals) were included in quantitative analyses. The overall pooled prevalence of FS, FA and CPFA in individuals with AD were 48.4% (95% confidence interval: 43.7-53.2), 32.7% (28.8-36.6) and 40.7% (34.1-47.5) respectively. AD prevalence among individuals with FS, FA and CPFA were 51.2% (46.3-56.2), 45.3% (41.4-49.3) and 54.9% (47.0-62.8) respectively. Children with AD had higher pooled FS (49.8% (44.4-55.1)) and FA (31.4% (26.9-36.1)) prevalences than adults with AD (28.6% (13.4-46.8) and 24.1% (12.1-38.7) respectively). Prevalences of FS and FA numerically increased with AD severity. FS, FA and CPFA are common comorbidities of AD and are closely related. Physicians should be attentive to this relationship to optimize management and treatment strategies in patients.
Assuntos
Dermatite Atópica , Hipersensibilidade Alimentar , Criança , Adulto , Humanos , Dermatite Atópica/epidemiologia , Dermatite Atópica/complicações , Prevalência , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/epidemiologia , Inflamação/complicações , Gravidade do PacienteRESUMO
BACKGROUND: Abrocitinib improved signs and symptoms of moderate-to-severe atopic dermatitis (AD) at Weeks 12 and 16 in phase 3 studies, with a manageable safety profile. Patient-reported outcomes with long-term abrocitinib treatment were not reported. OBJECTIVE: To evaluate patient-reported outcomes with long-term abrocitinib treatment in patients with moderate-to-severe AD. METHODS: JADE EXTEND (NCT03422822) is an ongoing, phase 3, long-term extension study that enrolled patients from previous abrocitinib AD trials. This analysis includes patients from the phase 3 trials JADE MONO-1 (NCT03349060), JADE MONO-2 (NCT03575871) and JADE COMPARE (NCT03720470) who completed the full treatment period of placebo or abrocitinib (200 or 100 mg once daily) and subsequently entered JADE EXTEND and were randomised to receive once-daily abrocitinib 200 or 100 mg. Patient-reported endpoints to Week 48 included the proportion of patients who achieved Dermatology Life Quality Index (DLQI) scores of 0/1 (no effect of AD on quality of life [QoL]) and a ≥4-point improvement in Patient-Oriented Eczema Measure (POEM) score (clinically meaningful improvement). Data cut-off: April 22, 2020. RESULTS: Baseline DLQI mean scores were 15.4 and 15.3 in the abrocitinib 200- and 100-mg groups, respectively, which corresponded to a 'very large effect' on QoL; at Week 48, mean DLQI scores were lower with abrocitinib 200 mg (4.6; 'small effect' on QoL) and abrocitinib 100 mg (5.9; 'moderate effect' on QoL). Baseline POEM mean scores were 20.4 and 20.5 in the abrocitinib 200- and 100-mg groups, respectively; at Week 48, mean POEM scores were 8.2 and 11.0. Week 48 patient-reported responses with abrocitinib 200 mg and abrocitinib 100 mg were 44% and 34% for DLQI 0/1, and 90% and 77% for a ≥4-point reduction in POEM score. CONCLUSION: In patients with moderate-to-severe AD, long-term abrocitinib treatment resulted in clinically meaningful improvement in patient-reported symptoms of AD, including QoL.
Assuntos
Dermatite Atópica , Humanos , Dermatite Atópica/terapia , Método Duplo-Cego , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Sleep disturbance (SD) is an important part of the burden of atopic dermatitis (AD), but patient-reported outcomes that are easy to understand and interpret in the target population have been lacking. A daily, single-item, self-reported SD 11-point numerical rating scale (NRS) was recently developed to assess SD for patients with moderate-to-severe AD, but its psychometric properties have not yet been described. OBJECTIVES: To assess the psychometric properties of the SD NRS in patients with moderate-to-severe AD. METHODS: The psychometric properties of the SD NRS were assessed using data from a phase IIb clinical trial in 218 adults with moderate-to-severe AD. RESULTS: Test-retest reliability of the SD NRS was substantial to almost perfect (interclass correlation 0·66-1·00) in participants who had stable SD or stable pruritus scores over 1 week. Baseline correlations were moderate to large (r > 0·30) between SD NRS and pruritus or sleep loss scores, but were small (r = -0·11 to 0·17) between SD NRS and EQ-5D-3L index and visual analogue scores, Hospital Anxiety and Depression Scale, Scoring Atopic Dermatitis, and Investigator's Global Assessment. The SD NRS could discriminate groups of participants in the expected direction according to different quality-of-life scores but not according to different clinician-reported disease severity scores. SD NRS scores significantly decreased as sleep loss, itch and quality-of-life scores improved. Analysis of meaningful change suggested a 2-5-point improvement as the initial range of responder definition in the SD NRS score. CONCLUSIONS: The SD NRS is a reliable, valid and responsive measure of SD in adults with moderate-to-severe AD.
Assuntos
Dermatite Atópica , Adulto , Dermatite Atópica/complicações , Dermatite Atópica/diagnóstico , Humanos , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , SonoRESUMO
BACKGROUND: Previous studies have found conflicting results about the association of atopic dermatitis (AD) with hypertension. OBJECTIVES: To determine whether AD and AD severity are associated with hypertension. METHODS: A systematic review was performed of published studies in Ovid MEDLINE, Embase, Scopus, Web of Science, and GREAT (Global Resource for EczemA Trials) databases. At least two reviewers conducted title/abstract, full-text review and data extraction. Quality of evidence was assessed using the Newcastle-Ottawa Scale. RESULTS: Fifty-one studies met the inclusion criteria and 19 had sufficient data for meta-analysis. AD was associated with higher odds of hypertension compared with healthy controls [increased in nine of 16 studies; pooled prevalence 16·4% vs. 13·8%; random-effects regression, pooled unadjusted odds ratio (OR) 1·16, 95% confidence interval (CI) 1·04-1·30], but lower odds of hypertension compared with psoriasis [decreased in five of eight studies; 15·4% vs. 24·8% (OR 0·53, 95% CI 0·37-0·76)]. In particular, moderate-to-severe AD was associated with hypertension compared with healthy controls [increased in four of six studies; 24·9% vs. 14·7% (OR 2·33, 95% CI 1·10-4·94)]. Hypertension was commonly reported as an adverse event secondary to AD treatments, particularly systemic ciclosporin A. Limitations include lack of longitudinal studies or individual-level data, and potential confounding. CONCLUSIONS: AD, particularly moderate-to-severe disease, was associated with increased hypertension compared with healthy controls, but with lower odds than for psoriasis.
Assuntos
Dermatite Atópica , Eczema , Hipertensão , Dermatite Atópica/complicações , Dermatite Atópica/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Anamnese , PrevalênciaRESUMO
BACKGROUND: The real-world course of health-related quality of life (HRQoL) in atopic dermatitis (AD) is not well established. AIM: To examine predictors, longitudinal course and phenotypes of HRQoL in adult patients with AD. METHODS: This was a prospective dermatology-practice based study of 955 patients with AD (age 18-97 years). Patients were assessed at baseline and approximately 6, 12, 18 and 24 months. HRQoL was assessed using the 10-item short-form Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health (PGH). AD severity and impact was assessed by patient-reported global AD severity, Patient-Oriented Eczema Measure (POEM), Eczema Area and Severity Index (EASI), Objective SCORing Atopic Dermatitis (O-SCORAD), Investigator's Global Assessment (IGA), Numerical Rating Scale (NRS) average and worst itch, PROMIS sleep-related impairment (SRI), and nine-item Patient Health Questionnaire (PHQ)-9. Repeated-measures regression models were constructed to examine itch over time. RESULTS: In multivariable linear regression models controlling for age, race/ethnicity, history of asthma, hay fever and food allergy, baseline PGH-physical (PGH-P4) T scores were inversely associated with patient-reported global AD severity, POEM, EASI, objective SCORAD, IGA, NRS average and worst itch, PROMIS SRI and PHQ-9, with stepwise decreases of physical health with worsening severity. PGH-mental health (PGH-M4) T scores were associated with all aforementioned severity measures aside from POEM. In multivariable repeated measures linear regression models, decreased PGH-P4 and PGH-M4 T scores and mapped five-dimension EuroQoL over time were associated with self-reported global AD severity, NRS worst and mean itch, POEM, PROMIS sleep disturbance and SRI, EASI, objective SCORAD, IGA and PHQ-9. Latent class analysis identified six classes of HRQoL, which were associated with measures of AD severity, nonwhite race, Hispanic ethnicity and having only public health insurance, but not age or sex. CONCLUSION: Patients with AD have a heterogeneous longitudinal course and distinct patterns of HRQoL. Many patients had fluctuating HRQoL over time. Most patients with moderate to severe disease at baseline had persistent HRQoL impairment over time.
Assuntos
Dermatite Atópica , Qualidade de Vida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Dermatite Atópica/complicações , Feminino , Humanos , Análise de Classes Latentes , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Once-daily abrocitinib treatment provided meaningful improvements in signs and symptoms of moderate-to-severe atopic dermatitis (AD) in randomized controlled studies. OBJECTIVE: To evaluate proportions of patients with responses meeting higher threshold efficacy responses than commonly used efficacy end points and to determine if these responses were associated with quality-of-life (QoL) benefits. METHODS: Data from a phase 2b (NCT02780167) and two phase 3 studies (NCT03349060/JADE MONO-1; NCT03575871/JADE MONO-2) in adult and adolescent patients (N = 942) with moderate-to-severe AD receiving once-daily abrocitinib 200 mg, abrocitinib 100 mg or placebo were pooled. Commonly used (Eczema Area and Severity Index [EASI]-75 and ≥4-point improvement in Pruritus Numerical Rating Scale [PP-NRS4]) and higher threshold efficacy end points (EASI-90 to Assuntos
Dermatite Atópica
, Adolescente
, Adulto
, Criança
, Dermatite Atópica/diagnóstico
, Dermatite Atópica/tratamento farmacológico
, Método Duplo-Cego
, Humanos
, Pirimidinas
, Qualidade de Vida
, Índice de Gravidade de Doença
, Sulfonamidas
, Resultado do Tratamento
RESUMO
Atopic dermatitis (AD) is a chronic skin disease that significantly impacts patient quality of life (QoL). It is unknown whether patients and physicians have the same interpretation of AD burden. Unmet needs and AD disease burden were evaluated by comparing terminology used in social media with terminology used in scientific literature. AD terminology in social media was identified using the NetBase platform, and natural language processing was performed. Topics and words driving negative sentiment were evaluated overall and in relation to specific symptoms. The systematic review of scientific literature identified publications that included AD and QoL terms was identified from PubMed. Term analysis of titles and abstracts was conducted via natural language processing. The occurrence of topics and co-occurrence of words associated with QoL terms were evaluated. More than 3 million social media mentions (2018-2020) and 1519 scientific publications (2000-2020) were evaluated. There were more negative than positive social media mentions, and flare and pain were common symptoms driving negative sentiment. Face and hands were major drivers of negative sentiment in relation to AD symptoms in social media. Sleep and pain were often mentioned together. In scientific literature, pruritus and depression were the most frequently occurring symptoms. Similarly, pruritus was the most common AD symptom co-occurring with QoL terms in the assessed scientific literature. Social media analyses provide a unique view into the patient experience of AD. Symptoms driving negative sentiment in social media appear to be discordantly represented in scientific literature. Incorporating patient perspectives may improve disease understanding and management.
Assuntos
Dermatite Atópica , Mídias Sociais , Humanos , Dor , Prurido/etiologia , Qualidade de VidaRESUMO
BACKGROUND: Recent advances were made in characterizing the clinical heterogeneity of atopic dermatitis (AD). OBJECTIVE: To review the clinical domains contributing to AD heterogeneity and describe their importance in clinical practice. METHODS: We conducted a focused review of the published literature, including retrospective, observational, and prospective studies, clinical trials, and consensus guidelines. RESULTS: AD is associated with heterogeneous skin manifestations, symptoms, lesional severity, lesional extent, longitudinal course, burden of signs and symptoms, and comorbidities. Each of these domains characterizes a different aspect of AD and should be used to guide overall severity assessment and clinical management. Primary focus on any one specific clinical domain of AD is insufficient to describe the full burden of disease. CONCLUSION: Heterogeneity should be routinely considered during AD clinical encounters. J Drugs Dermatol. 2022;21(2):172-176. doi:10.36849/JDD.6408.
Assuntos
Dermatite Atópica , Eczema , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/epidemiologia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Itch is a cardinal feature of paediatric disorders and can impair quality of life. However, few studies have addressed symptoms and impacts of itch in paediatric patients. OBJECTIVES: We focused on understanding the child's experience of itch and the impact of itch specifically on affected children, including comparison with the adult experience. METHODS: Semistructured interviews (nine parents, 15 children with itch) explored concerns related to paediatric itch experiences and effects. Themes were compared with those of previous adult interviews. Literature was reviewed to identify the need for a more comprehensive measure of paediatric itch. RESULTS: Itch quality, intensity, duration and environmental triggers (sweating, climate change, stress and certain fabrics) are important aspects of the child's itch experience. Skin disruption, physical function, concentration, emotional reactions, stigma and relationships/social effects are itch impact themes that emerged. No paediatric-specific scale comprehensively captures the paediatric patient itch experience. However, differences between child and adult reports of itch-related pain, functional limitations, fatigue and restlessness, emotional reactions to itch, and treatment effects emphasize the need for a paediatric-specific measurement tool. CONCLUSIONS: Children and parents endorse the importance of capturing the paediatric-focused characteristics and impacts of itch in measuring disease severity and response to intervention.
Assuntos
Pais , Qualidade de Vida , Adulto , Ansiedade , Criança , Família , Humanos , Prurido/etiologiaRESUMO
BACKGROUND: Multiple strategies have been used to evaluate the minimal important change (MIC) of the Eczema Area and Severity Index (EASI) and Scoring Atopic Dermatitis (SCORAD). The meaningfulness of these MICs is not well established across all severities of atopic dermatitis (AD). OBJECTIVES: To determine the MIC of percentage and absolute improvement of EASI and SCORAD scores in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 826). An anchor-based approach was used to determine thresholds for the percentage and absolute MICs of EASI, SCORAD and objective SCORAD (O-SCORAD) at follow-up from baseline. RESULTS: One-grade improvements of Physician's Global Assessment (PGA) and validated Investigator Global Assessment scale for AD (vIGA-AD) were associated with 50%, 35% and 35% decreases of EASI, SCORAD and O-SCORAD, respectively. The thresholds for percentage MIC of EASI (Kruskal-Wallis test, P = 0·61), SCORAD (P = 0·07) and O-SCORAD (P = 0·09) were similar across baseline AD severities. One-grade improvements of PGA and vIGA-AD were associated with 14·0- and 14·9-point decreases of EASI, 19·9- and 14·9-point decreases of SCORAD, and 15·5- and 17·4-point decreases of O-SCORAD. The thresholds for the absolute MIC of EASI (P < 0·001), SCORAD (P < 0·001) and O-SCORAD (P < 0·001) significantly differed by baseline AD severity. Percentage and absolute MICs for EASI and SCORAD were associated with improvements of AD symptoms and quality of life. CONCLUSIONS: EASI 50, SCORAD 35 and O-SCORAD 35 were meaningful percentage MICs regardless of baseline AD severity. The absolute MICs for EASI, SCORAD and O-SCORAD varied by baseline AD severity.
Assuntos
Dermatite Atópica , Eczema , Adulto , Criança , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Humanos , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The worldwide incidence of cutaneous squamous cell carcinoma (cSCC) is increasing. OBJECTIVES: To evaluate the tumour burden of in situ and invasive cSCC in Iceland, where the population is exposed to limited ultraviolet radiation. METHODS: This whole-population study used the Icelandic Cancer Registry, which contains records of all in situ and invasive cSCC cases from 1981 to 2017. Incidence of cSCC was evaluated according to age, anatomical location, residence and multiplicity, and trends were assessed using joinpoint analysis. Age-standardized rates (WSR) and age-specific incidence rates per 100 000 person-years were calculated, along with cumulative and lifetime risks. RESULTS: Between 1981 and 2017, in situ cSCC WSR increased from 1·2 to 19·1 for men and from 2·0 to 22·3 for women. Invasive cSCC WSR rose from 4·6 to 14 for men and from 0·3 to 13·2 for women. The average number of in situ cSCC lesions was 1·71 per woman and 1·39 per man. Women developed more in situ cSCCs than invasive cSCCs in almost all anatomical locations, whereas men developed more invasive cSCCs, mostly on the head and neck. The rates of in situ cSCC were higher in Reykjavik compared with rural areas. Furthermore, women more commonly developed multiple in situ lesions. For lip cSCCs, invasive lesions occurred more frequently than in situ lesions among both sexes. Joinpoint analysis showed that in situ cSCC in women exhibited the most rapid incidence increase. CONCLUSIONS: cSCC has become an increasingly significant public health problem in Iceland. Tanning bed use and travelling abroad may contribute to skin cancer development. Public health efforts are needed to stem the behaviours leading to this rapid rise in cSCC.
Assuntos
Carcinoma in Situ , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Carcinoma in Situ/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/etiologia , Feminino , Humanos , Islândia/epidemiologia , Masculino , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Raios UltravioletaRESUMO
BACKGROUND: Multiple atopic dermatitis (AD) severity scales exist, with no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the Rajka-Langeland score and compare it with other clinician-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 427). RESULTS: Rajka-Langeland had good concurrent validity with the Eczema Area and Severity Index (Spearman rho = 0·63), SCORing AD (SCORAD) (rho = 0·61), objective-SCORAD (rho = 0·52) and body surface area (rho = 0·51); good convergent validity with the numeric rating scale average-itch (rho = 0·60) and worst-itch (rho = 0·59), Patient-Oriented Eczema Measure (rho = 0·57), Dermatology Life Quality Index (rho = 0·53), Patient-Reported Outcomes Measurement Information System Itch Questionnaire (rho = 0·35-0·55) in adults and/or children; fair discriminant validity for patient- and physician-reported global AD severity; good responsiveness to change of severity of AD and itch; good reliability; internal consistency; with no floor or ceiling effects. Interpretability bands (3, clear/almost clear; 4-5, mild; 6-7, moderate; 8-9, severe) and minimal clinically important difference (1 point) were established. CONCLUSIONS: The Rajka-Langeland score showed good construct validity, reliability, internal consistency and responsiveness in adults and children with AD.
Assuntos
Dermatite Atópica , Eczema , Adulto , Criança , Dermatite Atópica/diagnóstico , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Tralokinumab is a fully human monoclonal antibody that specifically neutralizes interleukin-13, a key driver of atopic dermatitis (AD). OBJECTIVES: To evaluate the efficacy and safety of tralokinumab in combination with topical corticosteroids (TCS) in patients with moderate-to-severe AD who were candidates for systemic therapy. METHODS: This was a double-blind, placebo plus TCS controlled phase III trial. Patients were randomized 2 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks (Q2W) with TCS as needed over 16 weeks. Patients who achieved an Investigator's Global Assessment (IGA) score of 0/1 and/or 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16 with tralokinumab were rerandomized 1 : 1 to tralokinumab Q2W or every 4 weeks (Q4W), with TCS as needed, for another 16 weeks. RESULTS: At week 16, more patients treated with tralokinumab than with placebo achieved IGA 0/1: 38·9% vs. 26·2% [difference (95% confidence interval): 12·4% (2·9-21·9); P = 0·015] and EASI 75: 56·0% vs. 35·7% [20·2% (9·8-30·6); P < 0·001]. Of the patients who were tralokinumab responders at week 16, 89·6% and 92·5% of those treated with tralokinumab Q2W and 77·6% and 90·8% treated with tralokinumab Q4W maintained an IGA 0/1 and EASI 75 response at week 32, respectively. Among patients who did not achieve IGA 0/1 and EASI 75 with tralokinumab Q2W at 16 weeks, 30·5% and 55·8% achieved these endpoints, respectively, at week 32. The overall incidence of adverse events was similar across treatment groups. CONCLUSIONS: Tralokinumab 300 mg in combination with TCS as needed was effective and well tolerated in patients with moderate-to-severe AD.
Assuntos
Dermatite Atópica , Eczema , Corticosteroides , Anticorpos Monoclonais , Anticorpos Monoclonais Humanizados , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Little is known about the aetiologies and relevant allergens in paediatric patients with hand eczema (HE). OBJECTIVES: To characterize the aetiologies and determine the proportion of positive and currently relevant allergens in children/adolescents (age < 18 years) with HE referred for patch testing. METHODS: A retrospective analysis (2000-2016) of North American Contact Dermatitis Group data was performed. RESULTS: Of 1634 paediatric patients, 237 (14·5%) had involvement of the hands. Final physician diagnoses included allergic contact dermatitis (49·4%), atopic dermatitis (37·1%) and irritant contact dermatitis (16·9%). In multivariable logistic regression models, employment was the only association with increased odds of any HE or primary HE. Children with HE vs. those without HE had similar proportions of positive patch tests (56·1% vs. 61·7%; χ2 -test, P = 0·11). The five most common currently relevant allergens were nickel, methylisothiazolinone, propylene glycol, decyl glucoside and lanolin. In multivariable logistic regression models of the top 20 relevant allergens, HE was associated with significantly higher odds of currently relevant reactions to lanolin, quaternium-15, Compositae mix, thiuram mix, 2-mercaptobenzathiazole and colophony. The allergens with the highest mean significance-prevalence index number were methylisothiazolinone, carba mix, thiuram mix, nickel and methylchloroisothiazolinone/methylisothiazolinone. CONCLUSIONS: Children with HE who were referred for patch testing had a high proportion of positive patch tests, which was similar to the proportion found in children without HE. Children with HE had a distinct and fairly narrow profile of currently relevant allergens.
Assuntos
Dermatite Alérgica de Contato , Eczema , Adolescente , Alérgenos/efeitos adversos , Criança , Dermatite Alérgica de Contato/diagnóstico , Dermatite Alérgica de Contato/epidemiologia , Dermatite Alérgica de Contato/etiologia , Eczema/induzido quimicamente , Eczema/diagnóstico , Eczema/epidemiologia , Humanos , América do Norte/epidemiologia , Testes do Emplastro , Estudos RetrospectivosRESUMO
Given the lack of head-to-head studies of systemic therapies in moderate-to-severe atopic dermatitis (AD), network meta-analyses (NMAs) can provide comparative efficacy and safety data to inform clinical decision-making. In this NMA, eligible randomized controlled trials (RCTs) published before 24 October 2019 were identified by a systematic literature review. Short-term (12-16 weeks) efficacy (Investigator's Global Assessment [IGA] and Eczema Area and Severity Index [EASI] responses), patient-reported outcomes (PROs) and safety data from each trial were abstracted and analysed separately for monotherapy and combination therapy (systemic plus topical anti-inflammatory therapy). RCTs were analysed in fixed-effects and random-effects Bayesian NMA models. Overall, 19 phase 2 and phase 3 RCTs of abrocitinib, baricitinib, dupilumab, lebrikizumab, nemolizumab, tralokinumab and upadacitinib were included. In monotherapy RCTs, upadacitinib 30 mg once daily (QD) had the numerically highest efficacy (83.6% achieved ≥50% improvement in EASI [EASI-50 response]), followed by abrocitinib 200 mg QD (74.6%), upadacitinib 15 mg QD (70.5%), dupilumab 300 mg every 2 weeks (Q2W) (63.4%) and abrocitinib 100 mg QD (56.7%). Similar trends in EASI-75 and EASI-90 response were observed. In combination therapy RCTs, abrocitinib 200 mg QD had the highest EASI-50 (86.6%), followed by dupilumab 300 mg Q2W (82.4%) and abrocitinib 100 mg QD (79.7%). Similar findings were observed for IGA response and PROs. In monotherapy and combination therapy RCTs, the probability of treatment-emergent adverse events (TEAEs) was higher among all active treatments than with placebo (except for dupilumab 300 mg Q2W [odds ratio (OR), 0.96; 95% credible interval (CrI), 0.45-2.18] and abrocitinib 100 mg QD [OR, 0.95; 95% CrI, 0.35-2.66] in combination therapy RCTs), although active treatments did not significantly differ from one another. Abrocitinib, dupilumab and upadacitinib were consistently the most effective systemic therapies in adult and adolescent patients with AD, with no significant TEAE differences in short-term RCTs.
Assuntos
Dermatite Atópica , Eczema , Adolescente , Adulto , Dermatite Atópica/tratamento farmacológico , Método Duplo-Cego , Humanos , Metanálise em Rede , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Multiple clinician-reported outcome measures exist for atopic dermatitis (AD) severity. However, there is no gold standard for use in clinical practice. OBJECTIVES: To determine the measurement properties of the product of validated Investigator's Global Assessment for AD (vIGA) and body surface area (BSA) overall or divided into six categories (cBSA: 0%/0.1, <10%/10, <30%/30, <50%/50, <70%/70 and <90%/90-100%) and compare with other clinician-reported and patient-reported outcomes in adults and children with AD. METHODS: We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 653). RESULTS: vIGA*BSA and vIGA*cBSA had good convergent validity with BSA (Spearman's ρ = 0.97 and 0.93), eczema area and severity index (ρ = 0.94 and 0.92), and objective SCORAD (ρ = 0.88 and 0.89); and weak-to-good convergent validity with Numeric Rating Scale average itch (ρ = 0.22 and 0.22) and worst itch (ρ = 0.27 and 0.28), Patient-Oriented Eczema Measure (ρ = 0.44 and 0.43), Dermatology Life Quality Index (ρ = 0.48 and 0.49), ItchyQOL (ρ = 0.45 and 0.46), PROMIS Sleep Disturbance (ρ = 0.46 and 0.37) and sleep-related impairment (ρ = 0.31 and 0.31) in adults and/or children; very good discriminant validity for physician-reported global AD severity; good responsiveness to change of severity of AD and itch; and good reliability (intraclass correlation coefficient [95% confidence interval]: 0.72 [0.60-0.81] and 0.74 [0.62-0.82]) with no floor or ceiling effects. Thresholds for interpretability bands and clinically important difference were established. CONCLUSIONS: vIGA*BSA and vIGA*cBSA scores showed good convergent and discriminant validity, reliability, responsiveness and interpretability in adults and children with AD, and were feasible for use in clinical practice. vIGA*BSA and vIGA*cBSA had slightly lower convergent validity than EASI or objective SCORAD, but might be more efficient to collect and score.
Assuntos
Dermatite Atópica , Eczema , Adulto , Superfície Corporal , Criança , Dermatite Atópica/diagnóstico , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Nemolizumab is a humanized anti-IL-31 receptor blocker in phase 3 for atopic dermatitis (AD). OBJECTIVE: Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate-to-severe AD. METHODS: Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate-to-severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP-NRS), Investigator's Global Assessment (IGA), changes in sleep and responders with ≥ 4-point improvement on PP-NRS. RESULTS: There was a significantly greater itch relief apparent by Day 2 (-22.8% vs -12.3% PP-NRS; P = 0.005) which continued to improve through week 16 (-68.5% vs -30.9% PP-NRS; P < 0.001). At week 16, PP-NRS ≥ 4-point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (-26.6% vs -9.0%; P < 0.001) which further improved till week 16 (-76.0% vs -36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (-68.6% vs. -42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab-treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002). Nemolizumab was safe and well-tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events. CONCLUSIONS: Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline.