Marco Simonacci

Efficacy and maintenance strategies of two-compound formulation calcipotriol and betamethasone dipropionate gel (Xamiol® gel) in the treatment of scalp psoriasis: results from a study in 885 patients

Background: Previous studies showed the efficacy of a formulation containing calcipotriol and betamethasone dipropionate for the treatment of psoriasis. Objective: To investigate maintenance strategies of a formulation containing calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) for the treatment of scalp psoriasis. Materials and methods: Nine-hundred and four patients were screened and randomised on a 1:1 basis in two groups: maintenance of two applications per week (group A) versus on-demand therapy (group B). Clinical evaluation was performed at weeks 0, 2, 4, 8 and 12. Results: Eight-hundred and eighty-five patients were randomised: 441 in group A and 444 in group B. From week 2, both groups showed a significant clinical improvement compared with baseline; at weeks 8 and 12, group A demonstrated a higher clinical response compared with group B (p < 0.05). This difference was statistically significant (OR 0.47, 95% CI 0.37, 0.60). Conclusions: The maintenance of twice-weekly application versus on-demand treatment of calcipotriol/betamethasone dipropionate gel is more effective and is associated with a lower rate of relapse.

Relationship between cause of referral and diagnostic outcome in pigmented lesion clinics: a multicentre survey of the Italian Multidisciplinary Group on Melanoma (gipme)

&NA; Pigmented lesion clinics (PLCs) are permanent units to which subjects presenting with suspicious pigmented skin lesions can be rapidly referred and which can provide a prompt response to an individuals concern about melanoma. However, little is known about the melanoma detection rate in these clinics, in particular with regard to intermediate risk populations. We report a survey involving more than 1000 subjects consecutively referred by family doctors to six Italian PLCs. Using a histological diagnosis of melanoma as the endpoint, the pooled melanoma detection rate at these PLCs was 1.5% (one melanoma for diagnosed every 64 subjects examined), and the ratio between the number of melanomas and benign lesions excised for diagnostic verification was 1: 5.8 (16 melanomas and 93 benign lesions). Almost all the melanomas (15 out of 16) were detected in subjects who had requested referral for a specific doubtful lesion (group A) or for the presence of melanoma risk factors (previous melanoma, large number of common and atypical naevi, family history of melanoma) (group B). Only one melanoma was detected amongst the 418 subjects seeking consultation for concern about their moles (group C) (P = 0.004). The positive and negative predictive values of the referral groups A and B combined were 2.5% and 99.7%, respectively. Since the probability of detecting a melanoma in subjects referred only for reassurance about their moles, which nevertheless represented 43% of the subjects examined, is very low, an optimized role for PLCs in melanoma prevention would be to limit consultation to subjects who present for examination of a specific lesion or who have one or more risk factors for melanoma.

Treating psoriasis with etanercept in Italian clinical practice: Prescribing practices and duration of remission following discontinuation

AbstractBackground: Conventional antipsoriatic therapies are often administered until remission, with treatment resumed in the case of relapse, in order to reduce the likelihood of cumulative, dose-dependent toxicities. Biological agents have been safely used in continuous therapy. Objective: To assess the use of etanercept for psoriasis in clinical practice in Italy. Methods: This was an observational study carried out in 13 dermatological centres across Italy in patients with plaque psoriasis (with a Psoriasis Area and Severity Index [PASI] score ≥10) treated with etanercept. The study comprised a treatment and subsequent discontinuation period. Patients were eligible if they had plaque psoriasis and had begun treatment with etanercept between 1 September 2007 and 1 April 2008. Patients were evaluable for the duration of discontinuation analysis if they achieved a PASI reduction ≥50% (PASI50) and a PASI score <10 at the end of treatment. Etanercept treatment was restarted if the PASI score reached ≥10 or the patient had a clinical relapse. Data were collected retrospectively up to June 2008 and prospectively between July 2008 and January 2009. Patients received etanercept during the treatment period, followed by no etanercept treatment (other psoriasis treatment permitted) during the discontinuation period, and etanercept again during re-treatment. The main outcome measures were: PASI scores (type A responders: PASI reduction ≥75% [PASI75]; type B responders: PASI50 and PASI final score <10), Dermatology Life Quality Index (DLQI) scores and body surface area (BSA) involvement. Time from discontinuation to retreatment was evaluated. Use of other antipsoriatic medications was recorded throughout. Results: Eighty-five patients were evaluable for the treatment period. Overall, 55 (64.7%) of these patients were prescribed etanercept 50 mg twice weekly. The mean treatment duration was approximately 25 weeks. In total, 79 patients (92.9%) were considered type B responders and 77 of these patients were evaluable for the duration of discontinuation analysis. Overall, 68/85 (80%) were type A responders. During the treatment period, 7/85 (8.2%) patients received other antipsoriatic therapies. Improvements in mean DLQI score (−71.5%) and mean BSA involvement (−79.2%) were also observed. Etanercept was well tolerated. During the discontinuation period, 40/77 (51.9%) patients used other antipsoriatic medications (group 1) and 37/77 (48.1%) did not (group 2). The mean duration of discontinuation was significantly longer in group 1 (174 days) than in group 2 (117 days, log-rank test: p = 0.0013). Conclusion: In clinical practice, the duration of discontinuation from etanercept was in accordance with previously reported data, and was longer in patients who received other antipsoriatic drugs during discontinuation of etanercept than in those who did not. High rates of PASI50 and PASI75 response were obtained with etanercept, and these rates were higher than those observed in controlled clinical studies. Etanercept treatment was flexible, effective and well tolerated, and was associated with improved quality of life.

Identifying locally advanced basal cell carcinoma eligible for treatment with vismodegib: an expert panel consensus

Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Most occur on the head and neck, where cosmetic and functional outcomes are critical. BCC can be locally destructive if not diagnosed early and treated appropriately. Surgery is the treatment of choice for the majority of high-risk lesions. Aggressive, recurrent or unresectable tumors can be difficult to manage. Until recently, no approved systemic therapy was available for locally advanced or metastatic BCC inappropriate for surgery or radiotherapy. Vismodegib provides a systemic treatment option. However, a consensus definition of advanced BCC is lacking. A multidisciplinary panel with expertise in oncology, dermatology, dermatologic surgery and radiation oncology proposes a consensus definition based on published evidence and clinical experience.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides

IntroductionBexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes.ObjectivesWe aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS.MethodsWe followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. “Mini” and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS).ResultsAfter induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades.ConclusionsWe observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

Differences in Clinicopathological Features and Distribution of Risk Factors in Italian Melanoma Patients

Background: No studies are available in the literature on the distribution of different melanoma features and risk factors in the Italian geographical areas. Objective: To identify the differences in clinical-pathological features of melanoma, the distribution of risk factors and sun exposure in various Italian macro-areas. Methods: Multicentric-observational study involving 1,472 melanoma cases (713 north, 345 centre, 414 south) from 26 referral centres belonging to the Italian Multidisciplinary Group for Melanoma. Results: Melanoma patients in northern regions are younger, with thinner melanoma, multiple primaries, lower-intermediate phototype and higher counts of naevi with respect to southern patients; detection of a primary was mostly connected with a physician examination, while relatives were more involved in the south. Northern patients reported a more frequent use of sunbeds and occurrence of sunburns before melanoma despite sunscreen use and a lower sun exposure during the central hours of the day. Conclusions: The understanding of differences in risk factors distribution could represent the basis for tailored prevention programmes.

Relationship Between Cause Of Referral And Diagnostic Outcome In Pigmented Lesion Clinics Aimed To Melanoma Screening: A Multicenter Survey Of The Italian Multidisciplinary Group On Melanoma (Gipme)

BackgroundPigmented lesion clinics (PLCs) are a permanent structure for the rapid referral of subjects presenting suspicious pigmented skin lesions and they represent a prompt response to an individuals concern about melanoma. However, little is known about the actual melanoma detection activity of these clinics, in particular in intermediate risk populations. MethodsWe report a survey involving more than 1,000 subjects consecutively referred by family doctors to six italian PLCs. Diagnostic measures refer to histologic diagnosis of melanoma. ResultsOverall, the pooled melanoma detection rate at PLCs was 1.5% (one melanoma diagnosed every 64 subjects examined), and the ratio between the number of melanomas and benign lesions excised for diagnostic verification was 1: 5.8 (16/93). Almost all melanomas (15 out of 16) were detected in subjects who requested referral for a specific doubtful lesion (group A) or for presence of melanoma risk factors (previous melanoma, large number of common and atypical nevi, family history) (group B). Only 1 melanoma was detected in 418 subjects seeking consultation for concern about their moles (group C) (P=0.004). The positive and negative predictive values of the causes of referral A+B combined were 2.5%, and 99.7%, respectively. ConclusionsSince the very low probability of detecting a melanoma in subjects referred only for reassurance about their moles, which nevertheless represented 43% of the subjects examined, the optimized role of PLCs in melanoma prevention strategy would be reached by limiting consultation to subjects who present for examination of a specific lesion or who present one or more risk factors for melanoma.

Effects of TNF-α inhibitors in patients with psoriasis and metabolic syndrome: a preliminary study

BACKGROUND Psoriasis is an inflammatory disease, that is increasingly being considered as a systemic disorder. Among associated comorbidities, metabolic syndrome plays an important role. The effects of biological therapies on metabolic syndrome is controversial. METHODS Thirty-one psoriatic patients with metabolic syndrome, eligible to treatment with anti-TNFα agents, were enrolled. Metabolic parameters were measured during 4 subsequent visits, one every 40 to 60 days. PASI, BSA and DLQI assessed the severity of psoriasis and the impact on quality of life. RESULTS We include 31 patients, 18 treated with etanercept and 13 with adalimumab. Metabolic parameters evaluated at V4 in both groups showed different trends in the blood glucose values: a slight decrease in adalimumab group, an increase in etanercept group, with an almost significant comparison test (p=0.073). Similarly, the lipid profile revealed an opposing trend, with an increase in triglycerides in adalimumab patients, and a decrease in the other group, without statistically significant differences. No statistically significant difference was recorded in HDL cholesterol. An improvement in systolic and diastolic pressure was appreciated in both groups, although not significantly. The waist circumference slightly decreased in both groups. PASI 75 score was reached in 60% of the patients. In addition, BSA and DLQI improved. CONCLUSIONS Our study showed a slight improvement of metabolic parameters, at times with a trend toward significance. Additional long-term studies and a larger number of patients are needed to more clearly define the association between psoriasis and cardiovascular disease and understand the effect of biological therapies on metabolic parameters.