RESUMO
Background: Novel approaches to photoprotection must go beyond classical MED measurements, as discoveries on the effect of UV radiation on skin paints a more complex and multi-pronged scenario with multitude of skin cell types involved. Of these, photoimmunoprotection emerges as a crucial factor that protects against skin cancer and photoaging. A novel immune parameter is enabled by the precise knowledge of the wavelength and dose of solar radiation that induces photoimmunosupression. Natural substances, that can play different roles in photoprotection as antioxidant, immune regulation, and DNA protection as well as its possible ability as sunscreen are the new goals in cosmetic industry. Objective: To analyze the effect of a specific natural extract from Polypodium leucotomos (PLE, Fernblock®), as part of topical sunscreen formulations to protect from photoimmunosuppression, as well as other deleterious biological effects of UV radiation. Methods: The possible sunscreen effect of PLE was analyzed by including 1% (w/w) PLE in four different galenic formulations containing different combinations of UVB and UVA organic and mineral filters. In vitro sun protection factor (SPF), UVA protection factor (UVA-PF), contact hypersensitivity factor (CHS), and human immunoprotection factor (HIF) were estimated following the same protocol as ISO 24443:2012 for in vitro UVA-PF determination. Results: PLE-containing formulations significantly reduced UV radiation reaching to skin. Combination of UVB and UVA filters with PLE increased SPF and UVAPF significantly. PLE also increased UV immune protection, by elevating the contact hypersensitivity factor and the human immunoprotective factor of the sunscreen formulations. Conclusion: This study confirms the double role of PLE in photoprotection. Together to the biological activity shown in previous works, the UV absorption properties of PLE confers a booster effect when it is supplemented in topical sunscreens increasing the protection not only at level of erythema and permanent pigment darkening but also against two photoimmunoprotection factors.
RESUMO
BACKGROUND: Registry studies broadly describing the safety of systemic drugs in psoriasis are needed. OBJECTIVE: To describe the safety findings of the systemic drugs acitretin, adalimumab, apremilast, cyclosporine, etanercept, infliximab, methotrexate, secukinumab, and ustekinumab used for the treatment of moderate to severe psoriasis in patients included in the Spanish Registry of Adverse Events for Biological Therapy in Dermatological Diseases (BIOBADADERM) Registry. METHODS: The incidence rate ratio (IRR) and adjusted IRR (including propensity scores) of identified adverse events for each drug, using methotrexate as reference, were determined by means of a prospective cohort. RESULTS: Our study included 2845 patients (8954 treatment cycles; 9642 patient-years). Ustekinumab and secukinumab had the lowest rate of adverse events for several of the system organ classes, with a statistically significant decreased rate ratio (IRR of <1), whereas cyclosporine and infliximab had the highest, with an increased rate ratio (IRR of ≥5). LIMITATIONS: Observational study, drug allocation not randomized, depletion of susceptibles, and prescribed doses not registered. CONCLUSION: Our data provide comparative safety information in the real-life setting that could help clinicians selecting between available products.
Assuntos
Psoríase/tratamento farmacológico , Adulto , Idoso , Terapia Biológica/efeitos adversos , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Espanha , Fatores de TempoRESUMO
The safety and stability of synthetic UV-filters and the procedures for evaluating the photoprotective capability of commercial sunscreens are under continuous review. The influence of pH and temperature stressors on the stability of certain Mycosporine-like amino acids (MAAs) isolated at high purity levels was examined. MAAs were highly stable at room temperature during 24 h at pH 4.5â»8.5. At 50 °C, MAAs showed instability at pH 10.5 while at 85 °C, progressive disappearances were observed for MAAs through the studied pH range. In alkaline conditions, their degradation was much faster. Mycosporine-serinol and porphyra-334 (+shinorine) were the most stable MAAs under the conditions tested. They were included in four cosmetically stable topical sunscreens, of which the Sun Protection Factor (SPF) and other Biological Effective Protection Factors (BEPFs) were calculated. The formulation containing these MAAs showed similar SPF and UVB-BEPFs values as those of the reference sunscreen, composed of synthetic UV absorbing filters in similar percentages, while UVA-BEPFs values were slightly lower. Current in vitro data strongly suggest that MAAs, as natural and safe UV-absorbing and antioxidant compounds, have high potential for protection against the diverse harmful effects of solar UV radiation. In addition, novel complementary in vitro tests for evaluation of commercial sunscreens efficacy are proposed.
Assuntos
Antioxidantes/farmacologia , Alga Marinha/química , Pele/efeitos dos fármacos , Protetores Solares/farmacologia , Raios Ultravioleta/efeitos adversos , Administração Cutânea , Aminoácidos/isolamento & purificação , Aminoácidos/farmacologia , Animais , Antioxidantes/isolamento & purificação , Cicloexanóis/isolamento & purificação , Cicloexanóis/farmacologia , Cicloexanonas/isolamento & purificação , Cicloexanonas/farmacologia , Cicloexilaminas/isolamento & purificação , Cicloexilaminas/farmacologia , Emulsões , Glicina/análogos & derivados , Glicina/isolamento & purificação , Glicina/farmacologia , Humanos , Líquens/química , Camundongos , Porphyra/química , Propilenoglicóis/isolamento & purificação , Propilenoglicóis/farmacologia , Pele/efeitos da radiação , Protetores Solares/isolamento & purificaçãoRESUMO
BACKGROUND: Identifying patients likely to have very good or bad results from systemic psoriasis therapy could improve efficiency of therapy. OBJECTIVE: To develop prognostic models for good or bad response to classic systemic drugs, anti-TNFs, and ustekinumab in psoriasis. METHODS: Multivariable logistic regression of a prospective multicenter cohort of psoriatic patients in clinical practice (6449 person-years of follow-up). We used as possible predictors demographic characteristics, comorbidities, characteristics of the psoriasis (type, PASI, arthritis), history of past therapy at entry in the cohort, and history of response to previous cycles while in the cohort. We defined good response to a treatment cycle as either cycle end due to disease remission or a cycle longer than 2 years that does not end later due to inefficacy in the follow-up period. Bad response to a treatment cycle was defined as a cycle that is finished due to inefficacy, based on the physician judgment, after more than 3 months of treatment. RESULTS: Patients with fewer previous therapies, lower body mass index, older at start of therapy, and with previous history of good responses to therapy are more likely to have positive results of therapy. However, the predictive characteristics of models are poor. CONCLUSION: Predictive models of clinical response to systemic drugs in psoriasis with the studied variables do not seem to outperform drug selection by a dermatologist.
Assuntos
Terapia Biológica , Fármacos Dermatológicos/uso terapêutico , Imunossupressores/uso terapêutico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ustekinumab/uso terapêutico , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. PATIENTS AND METHOD: This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. RESULTS: A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾ 2 mm, HR, > 3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P < 0.03). The stratified analysis showed that the effect of delay time was at the expense of the patients with a negative sentinel-node biopsy and without regression. CONCLUSION: Early sentinel-node biopsy is associated with worse survival in patients with cutaneous melanoma.
Assuntos
Linfonodos/patologia , Melanoma/secundário , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia , Listas de Espera , Adulto , Idoso , Intervalo Livre de Doença , Feminino , França , História Antiga , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/terapia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Espanha , Centros de Atenção Terciária , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To describe the use of systemic therapy for psoriasis (biologic and nonbiologic [classic] drugs) in patients not adequately represented in randomized controlled trials (RCTs) and the risk of serious adverse events (SAEs) in these patients. DESIGN: A registry inception cohort was used. SETTING: Thirteen dermatology departments in Spain participated. PATIENTS: A consecutive sample of patients treated with biologics and a systematic sample of patients treated with classic systemic therapy were evaluated. A total of 1042 patients (2179 person-years) were included. EXPOSURE: Inadequate representation in trials was defined as the presence of any of the following factors: elderly age (>70 years); type of psoriasis other than chronic plaque psoriasis; history of infection caused by hepatitis B, hepatitis C, or human immunodeficiency virus; history of cancer (excluding nonmelanoma skin cancer); and chronic renal or hepatic disease. MAIN OUTCOME MEASURES: Serious adverse events as defined by the International Conference on Harmonization were evaluated. RESULTS: In all, 29.8% of patients receiving systemic therapy for psoriasis would not have been eligible for RCTs. These individuals had an increased risk of SAEs (incidence rate ratio, 2.7; 95% CI, 1.5-4.7). Patients exposed to biologics had an adjusted increased risk of SAEs (incidence rate ratio, 2.3; 95% CI, 1.1-4.8) that was similar in patients eligible and ineligible for RCTs. CONCLUSIONS: Patients ineligible for RCTs are an important proportion (30%) of those receiving systemic therapy for psoriasis. These patients have a higher risk of SAEs and should be closely monitored. Patients exposed to biologics (whether these patients are eligible for RCTs or ineligible) are susceptible to the same increase in risk of SAEs, but biologics add to a higher baseline risk in patients who are ineligible for RCTs. The risk-benefit ratio in ineligible patients receiving biologics might be different from the ratio in eligible patients.