Shergill B.,University of Sussex |
Zokaie S.,LEO Pharma |
Patient Preference and Adherence | Year: 2014
Background: There is limited information on the patterns of use, adherence rates, and factors that impact adherence with topical treatments for actinic keratosis (AK). Objectives: To establish patterns of use and adherence with topical treatments for AK and to identify treatment-related factors that impact on adherence. Methods: A community-based, cross-sectional study was performed using a standardized questionnaire completed online or via telephone interview. Patients were stratified according to the presence of AK lesions on the scalp and/or other extremities; and presence of scarring resulting from treatment. Results: This study included 305 patients with AK who were currently using a patient-applied topical therapy for AK or had used one within the previous 12 months. In total, 88% (n = 268/305) of patients were either non-adherent, non-persistent or both non-adherent and non-persistent to topical therapy. Duration of treatment was associated with increasing rates of non-adherence (adjusted odds ratio [OR]; for treatment durations greater than 4 weeks, 2.2, P, 0.01): 52% of patients were non-adherent with 3-4 week treatment duration; 69% of patients with 4-8 week treatment duration; and 71% of patients with 6-12 week treatment duration. There were similar increases in non-persistence with increasing treatment duration (adjusted OR; for treatment durations greater than 4 weeks, 2.1, P, 0.05). Conclusion: This study found high rates of non-adherence and non-persistence in patients with AK. Duration of treatment was a significant factor contributing to non-adherence and non-persistence to topical treatments. Patient-applied topical therapies that require less frequent application and have shorter treatment duration may be associated with improved adherence rates. © 2014 Shergill et al.
Lebwohl M.,Mount Sinai School of Medicine |
Swanson N.,Oregon Health And Science University |
Anderson L.L.,Dermatology Associates of Tyler |
Melgaard A.,Data Management |
And 2 more authors.
New England Journal of Medicine | Year: 2012
BACKGROUND: Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field therapy) can eradicate clinical and subclinical actinic keratoses. Topical field therapy currently requires weeks or months of treatment. We investigated the efficacy and safety of a new topical field therapy for actinic keratosis, ingenol mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities). METHODS: In four multicenter, randomized, double-blind studies, we randomly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo (vehicle), self-applied to a 25-cm 2 contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities. Complete clearance (primary outcome) was assessed at 57 days, and local reactions were quantitatively measured. RESULTS: In a pooled analysis of the two trials involving the face and scalp, the rate of complete clearance was higher with ingenol mebutate than with placebo (42.2% vs. 3.7%, P<0.001). Local reactions peaked at day 4, with a mean maximum composite score of 9.1 on the local-skin-response scale (which ranges from 0 to 4 for six types of reaction, yielding a composite score of 0 to 24, with higher numbers indicating more severe reactions), rapidly decreased by day 8, and continued to decrease, approaching baseline scores by day 29. In a pooled analysis of the two trials involving the trunk and extremities, the rate of complete clearance was also higher with ingenol mebutate than with placebo (34.1% vs. 4.7%, P<0.001). Local skin reactions peaked between days 3 and 8 and declined rapidly, approaching baseline by day 29, with a mean maximum score of 6.8. Adverse events were generally mild to moderate in intensity and resolved without sequelae. CONCLUSIONS: Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses. (Funded by LEO Pharma; ClinicalTrials.gov numbers, NCT00742391, NCT00916006, NCT00915551, and NCT00942604.) Copyright © 2012 Massachusetts Medical Society.
Bornholdt J.,Copenhagen University |
Felding J.,LEO Pharma |
Kristensen J.L.,Copenhagen University
Journal of Organic Chemistry | Year: 2010
Enantiopure 3-substituted morpholines were assembled through ring-opening of a N-2-benzothiazolesulfonyl (Bts) activated aziridine with organocuprates followed by a ring annulation reaction with a vinylsulfonium salt under microwave conditions. Deprotection of the N-Bts group proceeds under very mild conditions with 2-mercaptoacetic acid and LiOH at rt. © 2010 American Chemical Society.
Kamp S.,Roskilde Hospital |
Fiehn A.M.,Roskilde Hospital |
Stenderup K.,Aarhus University Hospital |
Rosada C.,Aarhus University Hospital |
And 4 more authors.
British Journal of Dermatology | Year: 2011
Background: The pathogenesis of hidradenitis suppurativa (HS) is not clearly understood. The nomenclature suggests an important role for the apocrine glands but recent evidence implicates the pilosebaceous unit as a more likely candidate to play a central role in the pathogenesis. Objectives: Our aim was to estimate the volume of the follicular epithelium, the follicular lumen and the sebaceous glands of patients with HS and healthy controls by means of stereology. Methods: Four-millimetre punch biopsies were taken from 21 patients with HS and nine healthy controls, fixed in formalin, embedded in paraffin and stained with haematoxylin and eosin prior to volume estimation using the Cavalieri principle. Results: Sebaceous gland tissue could be visualized in only 10 of 15 suitable hair follicle biopsies from patients with HS but was present in all biopsies from healthy controls (P = 0·05) and the mean sebaceous gland volume per follicle was one-seventh of that of healthy controls (P = 0·03). There was no significant difference between patients with HS and healthy controls with regard to follicular epithelium and follicle lumen volume. Conclusions: Our results suggest that the absence or reduced volume of the sebaceous gland may play a role in the pathogenesis of HS. The presence of fibrosis suggests that sebaceous glands are obliterated early in the pathogenesis of HS. © 2011 British Association of Dermatologists.
Segaert S.,University Hospital Leuven |
Ropke M.,LEO Pharma
Journal of Drugs in Dermatology | Year: 2013
Topical corticosteroids and vitamin D analogs are well established as safe and effective first-line treatments for mild to moderate plaque psoriasis. They act via distinct and complementary mechanisms of action: vitamin D analogs primarily counter epidermal dysregulation, inhibiting epidermal hyperproliferation and inducing keratinocyte differentiation, whereas corticosteroids act primarily as immunosuppressors, targeting pro-inflammatory cytokines and chemokines. Furthermore, both agents have additional activity that may complement their main effects: vitamin D analogs have some immunomodulatory properties and corticosteroids may impact on keratinocyte differentiation. Based on their dominant mechanisms of action, there is a strong scientific rationale for the combination of corticosteroids and vitamin D analogs in the treatment of plaque psoriasis. Indeed, the combination has been shown to have a greater effect on the immune-mediated mechanisms of psoriasis than either monotherapy used alone. There is also a strong biological rationale for decreased side effects with the combination. Vitamin D may restore epidermal barrier function, which is impaired with corticosteroid use, and counteract steroid-induced skin atrophy. Corticosteroids may reduce perilesional skin irritation induced by vitamin D analogs. Although clinical data strongly support improved efficacy and tolerability with a combination of calcipotriol and betamethasone dipropionate, additional studies are needed to further investigate their underlying mechanisms. Copyright © 2013 Journal of Drugs in Dermatology.