RESUMEN
BACKGROUND: Phase III clinical trials of biotherapies for childhood psoriasis are designed for a selected population, which can differ from real-life patients. OBJECTIVE: Our objective was to assess the proportion of children with psoriasis that received biotherapy in the biological treatments for pediatric psoriasis (BiPe) cohort that would be excluded from phase III clinical trials of these treatments. METHODS: Data concerning initiation of the first biotherapy from all patients included in the BiPe cohort were analyzed. Ineligibility was assessed after applying the exclusion criteria used in the principal phase III trials of etanercept, adalimumab, and ustekinumab for childhood psoriasis. RESULTS: Of the 134 patients included, 73 (54.5%) were ineligible for at least one randomized controlled trial based on one or more exclusion criteria. Amongst the 63 children treated with etanercept, 35 (55.5%) were ineligible: 22 because of the type of psoriasis, 12 because of concomitant treatment, and six because of psoriasis severity based on psoriasis assessment severity index (PASI) and physician global assessment (PGA) scores (PASI < 12 and PGA < 3). Amongst the 44 children treated with adalimumab, 32 (72.7%) were ineligible: 17 because of the clinical type of psoriasis, 12 because of psoriasis severity (PASI < 20 and PGA < 4), and seven because of concomitant treatment. Amongst the 27 children patients treated with ustekinumab, 12 (44.4%) were ineligible: eight because of psoriasis severity (PASI < 12 and PGA < 3), five because of the clinical type of psoriasis, and one because of concomitant treatment. Drug survival and the frequency of serious adverse events did not differ between eligible and ineligible patients. CONCLUSION: The majority of children treated with biotherapies in real-life practice differ from those in phase III trials, most commonly because of the clinical type of their psoriasis, the disease severity being lower than required and the use of prior or concomitant psoriasis treatment. Efficacy and safety results from phase III clinical trials in selected populations may not sufficiently reflect what is seen in real life, thus results from real-life cohort studies are necessary.
Asunto(s)
Terapia Biológica/métodos , Psoriasis/tratamiento farmacológico , Adolescente , Femenino , Humanos , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Dupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials. OBJECTIVE: We sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort. METHODS: We included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up. RESULTS: We included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10-9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10-9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10-6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs. LIMITATIONS: No control group, missing data. CONCLUSION: This real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Conjuntivitis/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Eosinofilia/inducido químicamente , Seguridad del Paciente/estadística & datos numéricos , Adulto , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Estudios de Cohortes , Conjuntivitis/epidemiología , Dermatitis Atópica/diagnóstico , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Eosinofilia/epidemiología , Femenino , Francia , Humanos , Inyecciones Subcutáneas , Estimación de Kaplan-Meier , Masculino , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la EnfermedadAsunto(s)
Erupciones por Medicamentos/etiología , Clorhidrato de Erlotinib/administración & dosificación , Hibiscus/química , Piel/efectos de los fármacos , Té/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Clorhidrato de Erlotinib/efectos adversos , Femenino , Interacciones de Hierba-Droga , Humanos , Piel/patologíaRESUMEN
Whereas adverse effects induced by xenobiotics are mainly linked to the pharmacological effect, the adverse side-effects induced by biological agents (BA) are often target-related and linked to the biological consequences of their action. Based on these differences, an original classification of the adverse effects has been proposed. Five types of adverse effects induced by BA are described (α, ß, γ, δ, and ε). This classification provides a very useful scheme for a better understanding of these adverse effects. This approach should help to better characterize the pathogenic mechanisms involved and to optimize their management. Healthcare professionals should be aware of the specific risks related to this relatively new class of drugs. Close monitoring of these BA is therefore recommended.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Terapia Biológica/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/clasificación , Factores Inmunológicos/efectos adversos , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/diagnóstico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/etiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/terapia , HumanosRESUMEN
Human papillomaviruses (HPV) are found in most human epithelia and some tumors. Most HPV strains associated with cutaneous lesions belong to three types, named alpha, beta and gamma. Although the causal link between genital human papillomavirus infection and cervical neoplasia is well established, the role of beta-HPV in non melanoma skin cancers is unclear. HPV mainly causes benign cutaneous lesions on the hands and soles. Genital HPV infection is the most common sexually transmitted infection. It is generally asymptomatic. The genitals can be infected by two low-risk HPV types (6 and 11), which are responsible for benign anogenital warts (condylomata acuminata). The implications of anogenital warts in children are highly controversial as regards sexual abuse. Treatments (chemical, physical or immunological) are lengthy, expensive, inconvenient and often painful. Recurrence is frequent because of HPV persistence in perilesional skin.
Asunto(s)
Infecciones por Papillomavirus , Adulto , Niño , Condiloma Acuminado/diagnóstico , Condiloma Acuminado/terapia , Crioterapia , Legrado , Femenino , Humanos , Recién Nacido , Queratolíticos/administración & dosificación , Queratolíticos/uso terapéutico , Masculino , Persona de Mediana Edad , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por Papillomavirus/cirugía , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/transmisión , Infecciones por Papillomavirus/virología , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/terapia , Podofilino/administración & dosificación , Podofilino/uso terapéutico , Recurrencia , Factores de Tiempo , Enfermedades del Cuello del Útero/diagnóstico , Enfermedades del Cuello del Útero/terapia , Verrugas/diagnóstico , Verrugas/terapia , Verrugas/transmisiónRESUMEN
Ultraviolet (UV) light is known to induce skin cancers by causing DNA gene mutations and inducing immunosuppression. Taking advantage of these immunosuppressive capacities, UV light has been used, with different modalities, as an immunosuppressive therapy in a variety of diseases including allograft rejection and graft-versus-host disease. Phototherapy includes UVB irradiation, UVA irradiation, oral psoralen (+)UVA irradiation (PUVA), photodynamic therapy, and extracorporeal photopheresis, which consists of infusion of UVA-irradiated autologous leukocytes collected by apheresis and incubated with 8-methoxypsoralen. According to numerous experimental models and human data, there is increasing evidence that UVB irradiation and extracorporeal photopheresis can induce regulatory T cells and anticlonotypic activity. These therapies induce apoptosis of activated T cells or of extracorporally treated mononuclear cells, and up-regulate the expression of costimulary molecules and adhesion molecules on antigen presenting cells. UVB- or UVA-induced apoptotic cells could secrete immune suppressive cytokines (interleukin (IL)-4, IL-10). The processing and presentation of apoptotic T cell antigens from clones of pathogenic T cells by activated antigen presenting cells might explain the induction of systemic anticlonotypic activity by photopheresis. This induction of cell-mediated suppressive activity opens up future prospects with the aim of expanding regulatory T cells and/or anticlonotypic activity, especially by photopheresis in organ and cell transplantation.