RESUMO
BACKGROUND: The efficacy of biologic therapies is greater among biologic-naïve vs. biologic-experienced psoriasis patients. However, little is known as to whether prior use of other systemic therapies impacts secukinumab efficacy in patients with moderate-to-severe psoriasis. OBJECTIVE: To investigate the impact of prior exposure to systemic therapies upon the efficacy and safety of secukinumab 300 mg for moderate-to-severe psoriasis. METHODS: Post hoc analysis of six randomised controlled trials (RCTs) comparing secukinumab with placebo, ustekinumab or etanercept at 12 weeks of treatment. Data comparing secukinumab with placebo and ustekinumab were meta-analysed, while comparisons between secukinumab and etanercept were from a single RCT. Four subgroups of patients were assessed: (i) naïve to non-biologic systemics (NBS) and biologics; (ii) exposed to NBS but naïve to biologics; (iii) naïve to NBS but exposed to biologics; and (iv) exposed to NBS and biologics. Outcomes of interest included the following: investigator's global assessment (IGA) score, absolute psoriasis area and severity index (PASI) response, PASI 75, PASI 90 and PASI 100 responses, and dermatology life quality index (DLQI). Safety was also assessed. RESULTS: One thousand three hundred and eighty-three patients were included in the secukinumab vs. placebo meta-analysis: 1776 in the secukinumab vs. ustekinumab meta-analysis and 653 in the within-trial analyses of secukinumab vs. etanercept. For all subgroups, secukinumab was significantly more efficacious than placebo for all outcomes measured. Secukinumab generated greater responses in biologic-naïve patients, while prior NBS had a negligible impact on treatment response. Furthermore, secukinumab was more efficacious than both ustekinumab and etanercept on many outcomes, with an even greater difference for biologic-naïve than biologic-exposed patients. Safety results were consistent with individual clinical trial results. CONCLUSIONS: Twelve-week treatment with secukinumab 300 mg is consistently more efficacious than placebo, etanercept and ustekinumab in patients with moderate-to-severe psoriasis, regardless of prior exposure to biologics or NBS. Secukinumab had a comparable safety profile to both etanercept and ustekinumab.
Assuntos
Produtos Biológicos , Psoríase , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Humanos , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Resultado do Tratamento , UstekinumabRESUMO
BACKGROUND: Real-world biologic drug survival is an important proxy measure for effectiveness. Predictors of drug survival may help patients with psoriasis choose between biologic therapies. OBJECTIVES: (i) To assess the relative drug survival of adalimumab, ustekinumab and secukinumab in patients with psoriasis. (ii) To investigate predictors of biologic drug survival. METHODS: A prospective cohort study was performed in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) between November 2007 and August 2019. We performed survival analysis and fitted a flexible parametric survival model for biologic discontinuation due to ineffectiveness. RESULTS: In total 9652 patients were included: 5543 starting on adalimumab (57·4%), 991 on secukinumab (10·3%) and 3118 on ustekinumab (32·3%). The overall drug survivals of adalimumab, secukinumab and ustekinumab in year 1 were 0·78 [95% confidence interval (CI) 0·77-0·79], 0·88 (95% CI 0·86-0·91) and 0·88 (95% CI 0·87-0·89), respectively. The adjusted hazard ratios (adjHRs) for discontinuation of adalimumab and secukinumab compared with ustekinumab were 2·11 (95% CI 1·76-2·54) and 0·67 (95% CI 0·40-1·11), respectively. The presence of psoriatic arthritis predicted for survival in the adalimumab and secukinumab cohorts (adjHR 0·67, 95% CI 0·51-0·88 and 0·70, 95% CI 0·40-1·24, respectively), but for discontinuation in the ustekinumab cohort (adjHR 1·42, 95% CI 1·12-1·81). Previous exposure to biologic therapies predicted for discontinuation in the ustekinumab and secukinumab cohorts (adjHR 1·54, 95% CI 1·26-1·89 and 1·49, 95% CI 0·91-2·45, respectively) and for survival in the adalimumab cohort (adjHR 0·71, 95% CI 0·55-0·92). CONCLUSIONS: Secukinumab and ustekinumab have similar sustained drug survival, while adalimumab has a lower drug survival in patients with psoriasis. Psoriatic arthritis and previous biologic experience were predictors with differential effects between the biologic therapies. What is already known about this topic? There is conflicting evidence over the real-world drug survival of secukinumab in patients with psoriasis. Data from registries to date suggest that secukinumab has a lower drug survival than that reported from clinical trials. What does this study add? This study found that secukinumab and ustekinumab had similar sustained drug survival in the real world, while the drug survival of adalimumab was lower, suggesting that the real-world drug survival of secukinumab is higher than previously reported. We found that psoriatic arthritis and previous biologic experience had differential effects on drug discontinuation in the three biologic cohorts. These predictors may help patients and clinicians choose the most appropriate biologic therapy.
Assuntos
Produtos Biológicos , Preparações Farmacêuticas , Psoríase , Adalimumab , Anticorpos Monoclonais Humanizados , Estudos de Coortes , Dermatologistas , Etanercepte , Humanos , Fatores Imunológicos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Resultado do Tratamento , UstekinumabRESUMO
Teledermatology generally involves doctors taking images of patients; however, patients increasingly want to own or have easy access to their health data. MySkinSelfie ( http://myskinselfie.com) is a mobile phone application (app) designed to improve the quality, consistency and accessibility of patient-held photos, and was developed to give patients the ability to generate and hold their own skin images to help guide their skin care. This study assessed the usability of this app in a cohort of patients attending a National Health Service Dermatology clinic. Patients were asked to use the app but were not given specific tasks to achieve. Of the 102 patients recruited, 32 downloaded the app and registered an account, 21 took at least one photo (median 5, range 1-103) and 19 completed the usability questionnaire. The majority of questionnaire respondents found the app easy to use but were more neutral on whether it really helped them to manage their skin problem. MySkinSelfie has been shown to be easy to use. Self-monitoring of skin problems may be useful for a subset of patients, and this is likely to depend on diagnosis, age and other patient factors.
Assuntos
Aplicativos Móveis , Autocuidado/métodos , Dermatopatias/patologia , Telemedicina , Adulto , Idoso , Estudos de Coortes , Dermatologia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Satisfação do Paciente , Pele/patologia , Dermatopatias/diagnóstico , Dermatopatias/terapia , Smartphone , Inquéritos e Questionários , Interface Usuário-ComputadorRESUMO
BACKGROUND: Patients recruited in randomized controlled trials (RCTs) for biologic therapies in psoriasis are not fully representative of the real-world psoriasis population. OBJECTIVES: Firstly, to investigate whether patient characteristics are associated with being included in a psoriasis RCT. Secondly, to estimate the differences in the incidence of severe adverse events (SAEs) and the response rate between RCT and real-world populations of patients on biologic therapies for psoriasis using a standardization method. METHODS: Data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) were appended to individual participant-level data from two RCTs assessing ustekinumab in patients with psoriasis. Baseline variables were assessed for association of being in an RCT using a multivariable logistic regression model. Propensity score weights were derived to reweigh the registry population so that variables had the distribution of the trial population. We measured the C-statistic of the model with trial status as the dependent variable, and the risk differences in the incidence rate of SAEs in the first year and Psoriasis Area and Severity Index (PASI) after 6 months in the BADBIR cohort before and after weighting. RESULTS: In total 6790 registry and 2021 RCT participants were included. The multivariable logistic regression model had a C-statistic of 0.82 [95% confidence interval (CI) 0.81-0.83]. The risk differences for the incidence rate of SAEs and the proportion of patients with PASI < 1.5 were 9.27 (95% CI -3.91-22.5) per 1000 person-years and 0.95 (95% CI -1.98-4.15), respectively. CONCLUSIONS: Our results suggest that RCTs of biologic therapies in patients with psoriasis are not fully representative of the real-world population, but this lack of external validity does not account for the efficacy-effectiveness gap. What's already known about this topic? Patients with psoriasis who would not be eligible for randomized controlled trials (RCTs) investigating biologic therapies have a greater risk of serious adverse events and lower treatment effectiveness than patients who would have been eligible. What does this study add? Baseline patient characteristics were shown to be predictive of whether a patient would have been eligible for enrolment in an RCT for psoriasis biologic therapy. We did not find any efficacy-effectiveness gap between the sample representative of the real-world population of patients with psoriasis and the sample representative of the RCT population. Factors outside of baseline patient characteristics, such as observer effect and higher adherence in RCTs, may be more influential in any efficacy-effectiveness gap between trial and real-world populations of patients with psoriasis.
Assuntos
Produtos Biológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Seleção de Pacientes , Psoríase/tratamento farmacológico , Projetos de Pesquisa/normas , Adalimumab/administração & dosagem , Adalimumab/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos Biológicos/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Etanercepte/administração & dosagem , Etanercepte/efeitos adversos , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Psoríase/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Padrões de Referência , Sistema de Registros/normas , Sistema de Registros/estatística & dados numéricos , Resultado do Tratamento , Ustekinumab/administração & dosagem , Ustekinumab/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Hand eczema is a common inflammatory dermatosis that causes significant patient morbidity. Previous studies comparing psoralen-ultraviolet A (PUVA) with narrowband ultraviolet B (NB-UVB) have been small, nonrandomized and retrospective. OBJECTIVES: To conduct an observer-blinded randomized controlled pilot study using validated scoring criteria to compare immersion PUVA with NB-UVB for the treatment of chronic hand eczema unresponsive to topical steroids. METHODS: Sixty patients with hand eczema unresponsive to clobetasol propionate 0·05% were randomized to receive either immersion PUVA or NB-UVB twice weekly for 12 weeks with assessments at intervals of 4 weeks. The primary outcome measure was the proportion of patients achieving 'clear' or 'almost clear' Physician's Global Assessment (PGA) response at 12 weeks. Secondary outcome measures included assessment of the modified Total Lesion and Symptom Score (mTLSS) and the Dermatology Life Quality index (DLQI). RESULTS: In both treatment arms, 23 patients completed the 12-week assessment for the primary outcome measure. In the PUVA group, five patients achieved 'clear' and eight 'almost clear' [intention-to-treat (ITT) response rate 43%]. In the NB-UVB group, two achieved 'clear' and five 'almost clear' (ITT response rate 23%). For the secondary outcomes, median mTLSS scores were similar between groups at baseline (PUVA 9·5, NB-UVB 9) and at 12 weeks (PUVA 3, NB-UVB 4). Changes in DLQI were similar, with improvements in both groups. CONCLUSIONS: In this randomized pilot trial recruitment was challenging. After randomization, there were acceptable levels of compliance and safety in each treatment schedule, but lower levels of retention. Using validated scoring systems - PGA, mTLSS and DLQI - as measures of treatment response, the trial demonstrated that both PUVA and NB-UVB reduced the severity of chronic palmar hand eczema.
Assuntos
Eczema/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Terapia PUVA/métodos , Adulto , Idoso , Esquema de Medicação , Feminino , Ficusina/administração & dosagem , Ficusina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia PUVA/efeitos adversos , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Método Simples-Cego , Raios Ultravioleta , Adulto JovemRESUMO
BACKGROUND: There is a known association between psoriasis and heavy alcohol consumption. The association between heavy alcohol consumption and other inflammatory skin diseases remains to be defined. OBJECTIVES: To examine the prevalence of heavy drinking using the Alcohol Use Disorders Identification Test (AUDIT) in patients with inflammatory skin disease. METHODS: We conducted an observational cross-sectional study in a single hospital outpatient department. We recruited 609 patients with either psoriasis, eczema, cutaneous lupus or other inflammatory disorders, and a reference population with skin lesions. Primary outcome was the proportion of patients in each group with an alcohol use disorder (AUD). RESULTS: The observed prevalence of AUD was 30·6% in patients with psoriasis, 33·3% in those with eczema, 12·3% in those with cutaneous lupus, 21·8% in those with other inflammatory disease and 14·3% in those with non-inflammatory disease. Odds ratios (OR) for AUD in patients in the inflammatory groups compared with those in the noninflammatory groups, adjusted for age and sex, were as follows: psoriasis 1·65 [95% confidence interval (CI) 0·86-3·17], eczema 2·00 (95% CI 1·03-3·85), lupus 1·03 (95% CI 0·39-2·71), other inflammatory disease 1·32 (95% CI 0·68-2·56). ORs were reduced if also adjusted for Dermatology Life Quality Index (DLQI). The prevalence of DLQI ≥ 11 was 31·1% for psoriasis, 43·7% for eczema, 17·5% for cutaneous lupus, 17·2% for other inflammatory disease and 2·8% for noninflammatory disease. CONCLUSIONS: Patients with eczema attending a hospital clinic have been shown to have high levels of AUD of a similar level to patients with psoriasis and higher than patients with noninflammatory skin diseases.
Assuntos
Alcoolismo/complicações , Dermatopatias/psicologia , Adulto , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Ansiedade/etiologia , Estudos de Casos e Controles , Estudos Transversais , Eczema/psicologia , Feminino , Humanos , Lúpus Eritematoso Cutâneo/psicologia , Masculino , Pessoa de Meia-Idade , Psoríase/psicologia , Qualidade de Vida/psicologia , Adulto JovemRESUMO
Treatment of severe hand eczema (HE) that is resistant to topical potent corticosteroid treatment is challenging. In 2013, we surveyed 194 UK dermatologists to obtain information about their usual treatment pathways to inform the choice of the comparator in a trial of alitretinoin in severe HE (ALPHA trial); the results indicated that the treatment approaches favoured by UK dermatologists differ. Psoralen combined with ultraviolet A (PUVA) and alitretinoin were identified as the most frequent first-line treatment options for hyperkeratotic HE, whereas oral corticosteroids were identified as the most frequent first-line treatment for vesicular HE, followed by PUVA and alitretinoin. In terms of potential adverse effects of long-term or repeated use, oral steroids and ciclosporin A were reported to cause most concern. There is uncertainty about which treatment gives the best short and long-term outcomes, because of a lack of definitive randomised controlled trials evaluating the effectiveness of different treatment pathways in severe HE.
Assuntos
Dermatologistas , Eczema/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Ceratolíticos/uso terapêutico , Terapia PUVA/estatística & dados numéricos , Padrões de Prática Médica , Tretinoína/uso terapêutico , Administração Oral , Corticosteroides/uso terapêutico , Alitretinoína , Doença Crônica , Pesquisas sobre Atenção à Saúde , Humanos , Reino UnidoAssuntos
Fármacos Dermatológicos/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Adulto , Fármacos Dermatológicos/efeitos adversos , Feminino , Fertilização/efeitos dos fármacos , Humanos , Gravidez , Nascimento Prematuro/induzido quimicamente , Nascimento Prematuro/epidemiologia , Ustekinumab/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Photoadaptation describes the skin's ability to withstand an increased dose of ultraviolet (UV) radiation with repeated exposure, and this is the reason for exposure doses being increased during a course of phototherapy. However, directly measured data on photoadaptation are available only for broadband (BB) and not narrowband (NB)-UVB. OBJECTIVES: To measure photoadaptation to narrowband UVB. METHODS: We measured the degree of photoadaptation in patients with psoriasis during a standard course of NB-UVB phototherapy. The minimal erythemal dose (MED) was measured before and towards the end of a course of phototherapy. An adaptation factor (AF) was calculated for each patient using the ratio of final MED to initial MED. Sigmoid dose-response curves were also constructed. RESULTS: MED results were available for 50 patients (mean age 44 years, 28 female). The mean AF was 2·7 (95% confidence interval 2·4-3·0). There was no significant correlation between AF and skin type or initial MED. Dose-response curves were right shifted and parallel after phototherapy, and there was no significant difference in the maximum slope (P = 0·73). CONCLUSIONS: The photoadaptation caused by NB-UVB is considerably less than that reported for BB-UVB. The variation in photoadaptation between patients was not explained by skin type or baseline MED. Physical factors (such as tanning and epidermal thickening) are probably sufficient to account for photoadaptation, rather than downregulation of the inflammatory response. These data should help in the design of phototherapy protocols for NB-UVB to achieve optimal clearance of psoriasis.
Assuntos
Adaptação Fisiológica/efeitos da radiação , Pele/efeitos da radiação , Raios Ultravioleta , Adulto , Relação Dose-Resposta à Radiação , Feminino , Humanos , Masculino , Psoríase/radioterapia , Radiometria , Terapia Ultravioleta/métodosAssuntos
Dermatite Esfoliativa/terapia , Psoríase/terapia , Adulto , Produtos Biológicos/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Emprego/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Fototerapia/estatística & dados numéricos , Resultado do Tratamento , Reino UnidoAssuntos
Pênfigo/terapia , Administração Cutânea , Administração Oral , Corticosteroides/administração & dosagem , Assistência ao Convalescente , Vesícula/terapia , Quimioterapia Adjuvante , Criança , Técnicas de Laboratório Clínico/métodos , Fármacos Dermatológicos/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Previsões , Humanos , Técnicas de Imunoadsorção , Imunossupressores/uso terapêutico , Infusões Intravenosas , Cuidados de Enfermagem , Pênfigo/diagnóstico , Fotoferese/métodos , Troca Plasmática/métodos , Plasmaferese/métodos , Gravidez , Complicações na Gravidez/terapia , Recusa em Tratar , Indução de Remissão , Apoio SocialAssuntos
Atenção à Saúde/métodos , Dermatologia/métodos , Necessidades e Demandas de Serviços de Saúde , Hospitais Especializados , Pacientes Internados , Dermatopatias/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido , Adulto JovemRESUMO
Background: Sweet syndrome (SS) can be categorized as classical Sweet syndrome (CSS), malignancy-associated Sweet syndrome (MASS) or drug-induced Sweet syndrome (DISS). Appropriate categorization of patients with SS and identification of the associated trigger are essential to direct subsequent investigations and follow-up, especially given that 21% of cases are malignancy-associated. However, no published guidelines exist to guide this. Objective: To analyse the categorization, management and outcomes of patients with SS in order to propose a structured approach for investigation and follow-up. Methods: Retrospective data collection from the electronic records of patients diagnosed with SS between 1 January 2005 and 31 December 2018. Categorized and non-categorized patients were compared, and the yield rate of investigations and duration of follow-up were analysed. Results: Sixty-four patients were included with CSS (77%), MASS (20%) and DISS (3%). Of these, 34 (53%) cases were not categorized by the assessing clinicians, three of which were subsequently diagnosed with a malignancy, up to 19 months later. There was no significant difference in investigations performed between categorized and non-categorized patients and the yield rates were modest overall. Follow-up averaged 10.5 (16.8) months; non-categorized patients were followed-up for significantly longer than categorized patients (15.0 (21.2) vs. 5.4 (6.8) months, p < 0.05). Conclusion: The lack of a structured way to approach patients with SS can lead to under- or over-investigation, diagnostic delays of underlying conditions and unnecessary follow-up. An algorithm is proposed to identify the likely trigger and manage patients accordingly. Larger prospective studies are required to confirm the optimal approach to investigate and follow-up patients with SS.