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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.
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Adenosina/análogos & derivados , Psoriasis/diagnóstico , Psoriasis/tratamiento farmacológico , Estadística como Asunto , Adenosina/administración & dosificación , Administración Oral , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
There are a wide variety of disfiguring dermatological conditions whose pathologic substrate is represented by the unwanted deposition of collagen from dermal fibroblasts. Pirfenidone has demonstrated efficiency in the treatment of disordered collagen production when applied topically. Due to a similar mechanism of action, we also hypothesize that a similar medication, nintedanib, might have similar applications. We also propose that a liposomal technology may assist in the penetration of nintedanib and enhance its clinical effects.
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Psoriasis is a chronic inflammatory, autoimmune-mediated disease that affects millions of individuals worldwide. Advances in treatment with biological agents represented by monoclonal antibodies, such as TNF-α inhibitors (TNFI), IL-17A and IL-12/23 antagonists have not only benefited from outstanding clinical efficacy with lower side effects compared to conventional systemic therapy, but also raised the standards towards therapeutic success, fact reflected in the greater Psoriasis Area and Severity Index (PASI) response rates. However, due to their relatively recent introduction in clinical practice, and despite their proven superior efficacy, further research is needed for monitoring the eventual changes in treatment-induced parameters, especially of metabolic origin. In this respect, initial reports stress on one particular comorbidity associated with psoriasis-obesity-which seems to be not only a risk and result of the disease, but also an adverse effect of long-term therapy with some biologics. The consequent drug-induced increase in body mass index (BMI) of patients suffering from psoriasis undergoing biological treatment appears to contribute to the progression of the disease, promote drug discontinuation and reduce overall clinical efficacy of monoclonal antibodies. Therefore, we review herein the impact of body weight (BMI) increase on the biological treatment of psoriasis, to further investigate on its relationship with the disease and aid on the management of treatment schemes that take into account individual characteristics of patients, such as body mass, for a more efficient and personalized therapy approach.
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INTRODUCTION: Dissecting cellulitis of the scalp, or Hoffman disease, is described as an extremely rare condition. Clinically, it is represented by recurrent painful nodules, purulent drainage, interconnected sinus tracts and keloid formation, leading to scaring and cicatricial alopecia. Without a precise diagnosis and an adequate treatment, the repercussions consist of severe infectious complications along with psychological negative effects and serious aesthetic alterations. There is no standard treatment. In refractory cases, surgical management is reported. PATIENT CONCERNS: We report a case of a 65-year-old Caucasian male patient, with a 5-year history of Hoffman disease, who presented with multiple abscesses and sinus tracts of the scalp and patches of alopecia. The lesions were non-responsive to medical treatment. DIAGNOSIS: The diagnosis of DCS has been established on the basis of the clinical appearance and has been confirmed histopathologically. INTERVENTIONS: The patient underwent wide excision of the scalp, followed by reconstruction using free latissimus dorsi flap and covered by meshed split-thickness skin graft. OUTCOMES: Eighteen-month follow-up revealed complete remission of symptoms and lesions along with satisfactory cosmetic result. CONCLUSION: The scope of this case report is to raise awareness of the following aspects: Hoffman disease has an extremely low occurrence rate, a difficult differential diagnosis and no standard therapeutical strategy. It also highlights the effectiveness of scalpectomy and free latissimus dorsi flap covered by meshed split-thickness skin graft in treating a very advanced stage of the disease together with providing a natural contouring of the scalp. Ultimately, it discusses the other treatment alternatives.
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Celulitis (Flemón)/cirugía , Colgajos Tisulares Libres , Dermatosis del Cuero Cabelludo/cirugía , Trasplante de Piel/métodos , Anciano , Humanos , MasculinoRESUMEN
Prurigo (PP) and pruritic folliculitis of pregnancy (PFP) are poorly characterized entities. Traditionally classified under specific dermatoses of pregnancy, they were reclassified under a new umbrella entity, atopic eruption of pregnancy (AEP), which also includes atopic dermatitis (AD) that can worsen or present for the first time in pregnancy. Still, several aspects of AEP have not been adequately elucidated. It needs to be clarified whether it is the intrinsic ("nonallergic" or "atopiform dermatitis") or extrinsic (immunoglobulin E-associated) AD that is affected by pregnancy. Future studies need to examine the postpartum prognosis of AD that develops for the first time during gestation. A revision of diagnostic criteria of AEP will allow a more accurate estimate of its prevalence, as well as clarification of the relationship between AD and specific dermatoses, such as PP and PFP. In this context, this review discusses the history, epidemiologic data, clinicopathologic features, and management of these entities.
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Dermatitis Atópica/diagnóstico , Foliculitis/diagnóstico , Complicaciones del Embarazo/diagnóstico , Complicaciones del Embarazo/terapia , Prurigo/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/etiología , Femenino , Foliculitis/epidemiología , Foliculitis/terapia , Humanos , Embarazo , Complicaciones del Embarazo/epidemiología , Prurigo/tratamiento farmacológico , Prurigo/epidemiologíaRESUMEN
The authors made an attempt at treating tuberous sclerosis (Bourneville's disease) by means of dermabrasion. The technique and postoperative course are described. The immediate results were very encouraging, but in time returned to an appearance close to the initial one. In conclusion, dermabrasion is not an appropriate treatment for tuberous sclerosis.