Randomized, double-blind, double-dummy, vehicle-controlled study of ingenol mebutate gel 0.025% and 0.05% for actinic keratosis.

BACKGROUND: There is a need for improved medical approaches to the treatment of actinic keratosis. Ingenol mebutate, a diterpene ester extracted and purified from the plant Euphorbia peplus, is being evaluated as a topical therapy for actinic keratosis. OBJECTIVE: Assess the efficacy and safety of ingenol mebutate (formerly PEP005) gel at 3 dosing regimens for the treatment of actinic keratosis. METHODS: Patients with non-facial actinic keratoses applied vehicle gel for 3 days, ingenol mebutate gel, 0.025% for 3 days, or ingenol mebutate gel, 0.05% for 2 or 3 days, with an 8-week follow-up period. RESULTS: All 3 active treatments were significantly more effective than vehicle at clearing actinic keratosis lesions, with a dose response observed. The partial clearance rate (primary efficacy end point) for patients treated with ingenol mebutate gel ranged from 56.0% to 75.4% compared with 21.7% for vehicle gel (P = .0002 to P < .0001 vs vehicle). The complete clearance rate was also significantly higher (P < or = .0006) for patients in the ingenol mebutate gel treatment groups (range: 40.0% to 54.4%) compared with vehicle (11.7%), as was the baseline clearance rate (range: 42.0% to 57.9% for ingenol mebutate gel compared with 13.3% for vehicle, P < .0001 to .0007 vs vehicle). The median percentage reduction in baseline actinic keratosis lesions for patients treated with ingenol mebutate gel ranged from 75% to 100% compared with 0% for vehicle gel (P < .0001 vs vehicle). Active treatment was well tolerated at all dosages. The mechanism of action of this agent is the localized induction of necrosis followed by a transient inflammatory response, and this was manifested in most patients as transient local skin responses consisting primarily of erythema, flaking/scaling, and crusting. There was no evidence of treatment-related scarring. LIMITATIONS: Local skin responses may have suggested active treatment to investigators. CONCLUSIONS: Short-course, field-directed therapy with ingenol mebutate gel for actinic keratoses on non-facial sites seems to be effective with a favorable safety profile and potential benefits over topical agents that require a more prolonged course of treatment.

Patient-reported outcomes from a multicenter, randomized, vehicle-controlled clinical study of MAS063DP (Atopiclair) in the management of mild-to-moderate atopic dermatitis in adults.

BACKGROUND: MAS063DP (Atopiclair) is a topical cream approved for symptomatic relief in the treatment of atopic and contact dermatitis. METHODS: This was a multicenter, randomized, double-blind, vehicle-controlled study in adults with mild-moderate atopic dermatitis. Patients were given MAS063DP or vehicle (2:1) three times per day to areas affected by atopic dermatitis for up to 50 days. A patient global assessment change from baseline was determined at days 8, 22, 36, and 50. Patient total body pruritus (visual analog scale) and patient opinion on treatment acceptability were also assessed. RESULTS: A total of 218 patients (active: n = 145, vehicle: n = 73) were enrolled. At Day 22, 77% of patients on MAS063DP had a patient global assessment of good improvement or better versus 21% on vehicle (p<0.0001, chi-squared test). Similarly, more patients had improvement in itch over their total body on MAS063DP than on vehicle (p<0.0001). CONCLUSION: MAS063DP treatment results in patient-perceived improvements in mild-moderate atopic dermatitis.

Effect of a single course of isotretinoin therapy on bone mineral density in adolescent patients with severe, recalcitrant, nodular acne.

BACKGROUND: Adverse changes in bone have been reported for patients undergoing high-dose, long-term (several years) isotretinoin therapy for disorders of cornification. The effect of short-term (4-5 months) therapy at the lower dose recommended for acne on bone development in younger, growing adolescent (12-17 years) patients has not been well studied. OBJECTIVE: The purpose of the study was to evaluate the effect of a standard, single course of isotretinoin (Accutane) therapy on bone mineral density (BMD) of the lumbar spine and hip in adolescents ages 12 to 17 years with severe, recalcitrant, nodular acne. METHODS: In this open-label, multicenter study, 217 adolescents (81 girls) with severe, recalcitrant, nodular acne were enrolled and treated with isotretinoin twice daily with food at the recommended total dose of approximately 1 mg/kg for 16 to 20 weeks. BMD in the lumbar spine and hip was measured at baseline and at the end of therapy by dual energy radiograph absorptiometry. RESULTS: There was no clinically significant mean change in BMD measured at the lumbar spine (+1.4%, range: -4.9% to +12.3%) or total hip (-0.26%, range: -11.3% to +15.0%). Hyperostosis was not observed in any patient. Typical efficacy expected in the treatment of acne was observed. CONCLUSIONS: A 16- to 20-week course of isotretinoin treatment at the recommended dose for severe acne has no clinically significant effect on lumbar spine and total hip BMD in the adolescent (12-17 years) population.

Gel de diclofenaco tópico al 3 por ciento y ácidohialurónico al 2,5 por ciento para el tratamiento de lasqueratosis actínicas (QA) / Topical 3.0 por ciento diclofenac in 2.5 por ciento hyaluronan gel in the treatment of actinic keratoses

Antecedentes: Las queratosis actínicas (QA) son lesiones epidérmicas que tienen un potencial de diferenciarse en carcinoma de células escamosas (CCE) agresivo. El tratamiento de las mismas en un estadio precoz puede evitar el desarrollo de CCE. Las opciones de tratamiento actuales son muy destructivas y se asocian con efectos secundarios importantes. Los estudios preliminares sobre diclofenaco tópico fueron prometedores y originaron su evaluación para el tratamiento de las queratosis actínicas. En estudios anteriores se ha demostrado que un gel de diclofenaco al 3 por ciento y ácido hialurónico al 2,5 por ciento es eficaz para el tratamiento de QA y se tolera bien. Este estudio fue diseñado para explorar aun más el potencial terapéutico de este gel. Métodos: En este estudio aleatorio, con enmascaramiento doble y controlado por placebo, participaron pacientes ambulatorios con diagnóstico de cinco o más lesiones de QA contenidas en 1 a 3 bloques de 5 cm2. Los pacientes recibieron tratamiento activo (diclofenaco al 3 por ciento en gel de ácido hialurónico al 2,5 por ciento) o un vehículo de gel inactivo (ácido hialurónico) como placebo (0,5 g b.i.d. en cada área de tratamiento de 5 cm2 durante 90 días). Las valoraciones consistieron en puntuación del número de lesiones objetivo (PNLO), puntuación del número de lesiones acumuladas (PNLA) e índices de mejoría global, valorados separadamente por el investigador (IMGI) y por el paciente (IMGP).Resultados: Los resultados de 96 pacientes en el seguimiento (30 días después del tratamiento) indicaron que había una proporción significativamente mayor de pacientes que tenían una PNLO=0 en el grupo de tratamiento activo que en el grupo placebo (50 por ciento frente a 20 por ciento, p<0,001). También hubo una diferencia significativa entre los dos grupos en la PNLA, ya que esta puntuación fue 0 en el 47 por ciento de pacientes del grupo de tratamiento activo y sólo en el 19 por ciento de pacientes del grupo placebo (p<0,001). La proporción de pacientes con una puntuación 4 en el IMGI (mejoría completa) en el seguimiento fue del 47 por ciento en el grupo de tratamiento activo y sólo del 19 por ciento en el grupo placebo (p<0,001); en el IMGP, estos valores fueron 41 por ciento y 17 por ciento, p<0,001. Ambos tratamientos se toleraron bien, produciendo generalmente efectos secundarios relacionados con la piel. Conclusiones: El diclofenaco tópico al 3 por ciento en gel de ácido hialurónico al 2,5 por ciento fue eficaz en el tratamiento de la QA y se toleró bien (AU)