RESUMO
BACKGROUND: CF101, an adenosine A3 receptor agonist, is an orally bioavailable small molecule drug presenting an anti-psoriatic effect demonstrated in a Phase 2 clinical trial in psoriasis patients.
OBJECTIVE: To evaluate the safety and efficacy of CF101 treatment in a Phase 2/3 study in patients with moderate to severe plaque-type psoriasis.
METHODS: This multicenter, double-blind, 2-segment, placebo-controlled study randomized subjects with moderate to severe plaque psoriasis to CF101 1 or 2 mg, or placebo twice daily. At either week 12 (Segment 1) or 16 (Segment 2), the placebo group crossed over to CF101 BID through week 32 in an open-label fashion. At week 12, following an interim analysis, the CF101 1mg group was discontinued due to futility. The primary endpoint was proportion of patients achieving ≥75% improvement in Psoriasis Area Severity Index (PASI 75). Efficacy testing was performed using the Cochran-Mantel Haenszel test, the primary analysis of PASI 75 was performed at the 0.035 significance level.
RESULTS: CF101 had an excellent safety profile at all tested dosages with a profile similar to the placebo group. The most common adverse events were infections and gastrointestinal events, and there was no cumulative intolerance over the 32-week dosing period. The study did not meet the primary endpoint of PASI 75 at week 12 (2 mg: 8.5% vs. placebo: 6.9%, P=0.621). However, at week 32, PASI mean percent improvement with CF101 2 mg was 57% (P<0.001) compared to baseline, with linear improvement in PASI 50 (63.5%), 75 (35.5%), 90 (24.7%), and 100 (10.6%).
CONCLUSIONS: Oral CF101 was found to be safe and very well tolerated, demonstrating evidence of efficacy in patients with moderate to severe plaque psoriasis through 32 weeks of treatment.
J Drugs Dermatol. 2016;15(8):931-938.
Assuntos
Adenosina/análogos & derivados , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Estatística como Assunto , Adenosina/administração & dosagem , Administração Oral , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Combination therapy addressing multiple pathogenic factors should be used to achieve optimal outcomes in treating acne. The following study demonstrated both safety and efficacy of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide 2.5% in the morning with micronized tretinoin 0.05% gel in the evening. Both products were applied to the skin following the use of a ceramide containing moisturizing lotion.
Assuntos
Acne Vulgar/tratamento farmacológico , Peróxido de Benzoíla/administração & dosagem , Ceramidas/administração & dosagem , Clindamicina/análogos & derivados , Tretinoína/administração & dosagem , Acne Vulgar/patologia , Administração Cutânea , Adolescente , Adulto , Peróxido de Benzoíla/efeitos adversos , Ceramidas/efeitos adversos , Clindamicina/administração & dosagem , Clindamicina/efeitos adversos , Esquema de Medicação , Quimioterapia Combinada , Feminino , Géis , Humanos , Masculino , Resultado do Tratamento , Tretinoína/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: Psoriasis afflicts 2-3% of the world's population. Affected patients commonly have risk factors for cardiovascular disease (CVD). In addition, psoriasis is independently associated with CVD and mortality. PURPOSE: To determine which CVD risk factors are associated with psoriasis independent of confounders, whether psoriasis is associated with CVD independent of CVD risk factors, and whether there is increased mortality among patients with psoriasis. DATA SOURCES: MEDLINE, Embase, and Cochrane Collaborations from inception through October 2009. We reviewed bibliographies of retrieved articles for additional references. STUDY SELECTION: Cross-sectional, cohort-based, case-control, and randomized controlled trials which involved patients with psoriasis. DATA EXTRACTION: Two investigators independently reviewed studies and resolved any discrepancies by consensus. DATA SYNTHESIS: Of the 2,303 articles identified by literature search, 90 studies met inclusion criteria for this review; 15 were cohort-based studies, 45 were case-control, and 30 were cross-sectional. LIMITATIONS: The quality of evidence was limited by study heterogeneity and lack of large scale prospective studies with long-term follow-up. CONCLUSIONS: Patients with psoriasis demonstrate a higher prevalence of cardiovascular risk factors and appear to be at increased risk for ischemic heart disease, cerebrovascular disease, and peripheral arterial disease. This increase in vascular disease may be independent of shared risk factors and may contribute to the increase in all-cause mortality. Future research should aim to more confidently distinguish between a true causal relationship or merely an association resulting from multiple shared risk factors. Physicians should screen for and aggressively treat modifiable risk factors for CVD in patients with psoriasis.
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Psoríase/epidemiologia , Psoríase/terapia , Doenças Vasculares/epidemiologia , Doenças Vasculares/terapia , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Estudos Prospectivos , Psoríase/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fatores de Risco , Resultado do Tratamento , Doenças Vasculares/diagnósticoRESUMO
Topical corticosteroids have been the mainstay of treatment for atopic dermatitis (AD) over the last decade, especially in the setting of acute flares. However, heavy and prolonged use of topical corticosteroid is undesirable as it is associated with side effects such as, skin atrophy, telangiectasia, striae, steroid-induced dermatoses, rosacea, acne exacerbation, and in some severe and rare cases, systemic effects such as hypothalamic-pituitary-adrenal axis suppression, growth retardation and ocular problems. Non-steroidal ant-inflammatory agents specific for the treatment of AD (topical calcineurin inhibitors, or TCIs) are now available and they are a viable alternative to topical corticosteroids in treating dermatitis of the face, neck, eyelids, and intertriginous areas where there is a greater risk of the steroid-induced side effects. More recently, medical device emollients have entered the marketplace. These medical devices provide, but are not limited to, anti-oxidant, anti-protease, anti-inflammatory activity, and aid in restoring the natural balance of lipids, which is one of the causes of the epidermal abnormalities seen with AD. The present study evaluated the short-term effectiveness and appeal of a non-steroidal medicated device foam as compared to pimecrolimus cream 1% in the treatment of AD within a wide age group of subjects with active disease at baseline. In this study, both pimecrolimus and the medical device foam exhibited efficacy in mild-to-moderate AD. Primary efficacy was measured by IGA. After four weeks of treatment with the medical device foam, 82% of target lesions were scored "clear" (0) or "almost clear" (1) compared to 71% of target lesions under the pimecrolimus arm. This study confirmed that pimecrolimus cream 1% and the medical device foam work well in the treatment of AD in both adults and children with no associated adverse effects.
Assuntos
Ceramidas/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Ácido Hialurônico/uso terapêutico , Tacrolimo/análogos & derivados , Administração Cutânea , Adolescente , Adulto , Idoso , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Ceramidas/administração & dosagem , Ceramidas/efeitos adversos , Criança , Pré-Escolar , Dermatite Atópica/patologia , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Combinação de Medicamentos , Feminino , Seguimentos , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: There are multiple therapeutic options for the treatment of moderate to severe psoriasis. The process of choosing among potential treatment options requires both the physician and the patient to weigh the benefits of individual modalities against their potential risks. Traditional systemic therapies for psoriasis, including methotrexate (MTX) and cyclosporine (CsA), have a well-documented array of toxicities, particularly end-organ toxicities. Over the past several years, the use of biologic therapies for the treatment of moderate to severe psoriasis has been a major clinical and research focus. With the advent of these novel immunosuppressive therapies, one of the central safety issues surrounding these agents is their potential to increase the risk of malignancy. OBJECTIVE: Our objective was to review the risk of malignancy associated with therapies for moderate to severe psoriasis, including phototherapy, traditional systemic therapies, and biologic therapies. We reviewed the existing body of literature in order to define the known incidence of malignancy associated with psoralen and ultraviolet A (PUVA), narrowband and broadband ultraviolet B (UVB), MTX, CsA, mycophenolate mofetil (MMF), and biologic therapies, including alefacept, efalizumab, infliximab, etanercept, adalimumab, and ustekinumab. RESULTS: PUVA, when given long term, is associated with increased risks of cutaneous squamous cell carcinoma and malignant melanoma. Reviews of studies on UVB, both narrowband and broadband, do not indicate any increased risk of nonmelanoma skin cancer or melanoma. The traditional systemic psoriasis therapies-MTX, CsA, and MMF-may be associated with an increased risk of lymphoproliferative disorders during treatment, demonstrated in clinical trials in patients with rheumatoid arthritis and documented in case reports concerning psoriasis patients. The risk of malignancy with biologic therapy is still unclear. However, the majority of studies examining this carcinogenic risk suggest that tumor necrosis factor-alpha inhibitors may cause a slightly increased risk of cancer, including nonmelanoma skin cancer and hematologic malignancies. LIMITATIONS: The majority of studies cited in this review lack the power and randomization of large clinical trials, as well as the long-term follow-up periods which would further substantiate the hypothetical link between these antipsoriatic treatment regimens and the potential for malignancy. Because of the substantial lack of clinical data, the majority of studies evaluated focus on the treatment of patients with rheumatoid arthritis, which is a systemic inflammatory disorder comparable to psoriasis. Additionally, the increased risk of malignancy associated with psoriasis itself is a confounding factor. CONCLUSION: Many of the therapies for moderate to severe psoriasis, including PUVA, traditional systemic therapies, and some biologic therapies, may increase the risk of malignancy. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with these agents. Further long-term study is necessary to more precisely quantify the risks associated with biologic therapies.
Assuntos
Psoríase/terapia , Neoplasias Cutâneas/etiologia , Produtos Biológicos/efeitos adversos , Ciclosporina/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Humanos , Metotrexato/efeitos adversos , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/análogos & derivados , Terapia PUVA/efeitos adversos , Psoríase/tratamento farmacológico , Neoplasias Cutâneas/induzido quimicamente , Terapia Ultravioleta/efeitos adversosRESUMO
Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)-infected population. The presentation of psoriasis in patients with HIV varies. It either presents as the first clinical manifestation of HIV or, less commonly, appears in the advanced stages of HIV when it has progressed to AIDS. This 2-part series reviews the pathogenesis of HIV-associated psoriasis as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV These therapies address the profound immune dysregulation that defines psoriasis. The first part of the series focuses on the pathogenesis of HIV-associated psoriasis.
Assuntos
Infecções por HIV/imunologia , Psoríase/imunologia , Citocinas/imunologia , Infecções por HIV/complicações , Humanos , Psoríase/etiologia , Psoríase/patologia , Linfócitos T/imunologiaRESUMO
Psoriasis is a chronic, immune-mediated skin disease affecting approximately 1% to 3% of the human immunodeficiency virus (HIV)-infected population. Psoriasis appears in patients with HIV either as the first clinical manifestation of the disease or, less commonly, during the advanced stages of HIV when it has progressed to AIDS. This 2-part series reviews the pathogenesis of HIV-associated psoriasis as well as the various therapeutic regimens that have effectively treated psoriasis in patients with HIV. These therapies address the profound immune dysregulation that defines psoriasis. The second part of the series focuses on the treatment of HIV-associated psoriasis.
Assuntos
Infecções por HIV/imunologia , Psoríase/imunologia , Psoríase/terapia , Infecções por HIV/complicações , Humanos , Hospedeiro Imunocomprometido , Psoríase/etiologiaRESUMO
External genital warts, also known as condylomata acuminata, are extremely common, with between 500,000 to one million new cases diagnosed each year in the United States alone. To date, more than 120 distinct subtypes of human papillomavirus have been identified. Human papillomavirus types 6 and 11 rarely give rise to cervical cancers, but are responsible for 90 percent of the cases of genital warts. The current treatment options are largely centered upon removal of the warts rather than elimination of the underlying viral infection. A wide range of therapies are presently in use, which are highly variable and can differ dramatically with respect to cost, side-effect profiles, dosing schedules, duration of treatment, and overall effectiveness. As of yet, no definitive therapy has emerged as the ideal standard of care in the treatment of genital warts, and therapy selection generally occurs in a patient-specific manner.
RESUMO
This article reviews the recent dermatopathology literature involving nonmelanocytic neoplasia, with a focus on important work done over the last 5 years. The discussion includes advances in the understanding of Merkel cell carcinoma pathogenesis and prognosis; changes in the seventh edition of the American Joint Committee of Cancer staging manual in reference to staging of squamous cell carcinoma and Merkel cell carcinoma; newly described or rare histopathologic patterns and entities including squamoid eccrine ductal carcinoma, rippled-pattern adnexal neoplasms, onychomatricoma, spindle cell predominant trichodiscoma/neurofollicular hamartoma, and myoepithelioma; and microsatellite instability in sebaceous neoplasms of Muir-Torre syndrome and other tumors.
Assuntos
Carcinoma de Célula de Merkel/patologia , Carcinoma de Células Escamosas/patologia , Poliomavírus das Células de Merkel , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/virologia , Acantoma/complicações , Acantoma/patologia , Adenocarcinoma Sebáceo/patologia , Adenoma/patologia , Carcinoma de Célula de Merkel/virologia , Carcinoma de Células Escamosas/virologia , Hamartoma/patologia , Humanos , Ceratoacantoma/patologia , Síndrome de Muir-Torre/complicações , Mioepitelioma/patologia , Estadiamento de Neoplasias , Infecções por Polyomavirus/patologia , Neoplasias das Glândulas Sebáceas/complicações , Neoplasias das Glândulas Sebáceas/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Infecções Tumorais por Vírus/patologiaRESUMO
Basal cell carcinoma is the most common form of nonmelanoma skin cancer in the United States. Treatment modalities include both surgical, medical, or combination therapy. In the following case, the authors report the successful treatment of a basal cell carcinoma on the nose with curettage followed by topical imiquimod 3.75% cream.
RESUMO
Atopic dermatitis, commonly known as eczema, is a common chronic, relapsing skin disease characterized by pruritus, disrupted epidermal barrier function, and immunoglobulin E-mediated sensitization to food and environmental allergens. Atopic dermatitis is a complex disease that arises from interactions between genes and the environment. Loci on several chromosomes have been identified, including a family of epithelium-related genes called the epidermal differentiation complex on chromosome 1q21. Mutations in filaggrin, a key protein in epidermal differentiation, have also been identified in early-onset and severe atopic dermatitis. There are 3 classical stages of eczema: infantile, childhood, and adulthood. The spectrum of eczema presentation varies widely from a variant that only affect the hand to major forms where a patient presents with erythroderma. The acute and subacute lesions of atopic dermatitis are often characterized by intensely pruritic, erythematous papules and vesicles with excoriations and a serous exudate. Chronic atopic dermatitis is exemplified by lichenified plaques and papules with excoriations. Atopic dermatitis patients are also at higher risk for skin infections, including bacterial and viral superinfections. Conventional therapy includes avoidance of irritants and potential allergens, as well as continued hydration of the skin with thick emollients. Topical corticosteroids and topical immunomodulators are often used primarily. Other therapies including phototherapy, antimicrobials, antihistamines, and systemic immunosuppressives are also options in certain situations.
Assuntos
Dermatite Atópica , Eczema , Dermatite Atópica/diagnóstico , Dermatite Atópica/epidemiologia , Dermatite Atópica/genética , Dermatite Atópica/terapia , Eczema/diagnóstico , Eczema/epidemiologia , Eczema/genética , Eczema/terapia , Proteínas Filagrinas , HumanosRESUMO
Estimates from the American Cancer Society suggest that there are more than two million cases of nonmelanoma skin cancer in the United States per year. The following review highlights the topics of actinic keratoses, basal cell carcinoma, squamous cell carcinoma, Kaposi's sarcoma, and Merkel cell carcinoma. This update on the cutting-edge clinical and dermpathologic research will assist the dermatologist in approaching, diagnosing, and managing nonmelanoma skin carcinoma. Immunologic and genetic research into nonmelanoma skin carcinoma has paved the way for novel therapeutic options for patients who were previously without any viable treatment alternatives. While still in preliminary stages, agents, such as ingenol mebutate, vismodegib, and sirolumus, may become integral drugs in the armamentarium of managing cutaneous carcinoma.