Ester Del Duca

Pharmacodynamic assessment of apremilast for the treatment of moderate-to-severe plaque psoriasis

ABSTRACT Introduction: Psoriasis is a chronic inflammatory skin disease affecting 2–3% of the population. Certain systemic drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. Moreover, tolerability issues, parenteral administration, and barriers to patient access, such as high cost and specialist management lead to treatment failure. Areas covered: Apremilast is an oral small molecule inhibitor of phosphodiesterase 4 (PDE4i). PDE is the major enzyme class responsible for the hydrolysis of cyclic adenosine monophosphate in immune cells (cAMP). With PDE4 inhibition, apremilast works intracellularly to modulate pro-inflammatory and anti-inflammatory mediator production critically involved in psoriasis. The aim of this paper is to focus the attention on apremilast pharmacodynamics effects, its efficacy and safety in treating moderate-to-severe plaque psoriasis. Expert opinion: Apremilast is an effective and well-tolerated option in treating moderate-to-severe plaque psoriasis. Its safety profile and the oral administration offer significant advantages in prescribing apremilast for the treatment of psoriasis, particularly in some subsets of patients.

Nonconventional Use of Flash-Lamp Pulsed-Dye Laser in Dermatology

Flash-lamp pulsed-dye laser (FPDL) is a nonablative technology, typically used in vascular malformation therapy due to its specificity for hemoglobin. FPDL treatments were performed in a large group of patients with persistent and/or recalcitrant different dermatological lesions with cutaneous microvessel involvement. In particular, 149 patients (73 males and 76 females) were treated. They were affected by the following dermatological disorders: angiokeratoma circumscriptum, genital and extragenital viral warts, striae rubrae, basal cell carcinoma, Kaposis sarcoma, angiolymphoid hyperplasia, and Jessner-Kanof disease. They all underwent various laser sessions. 89 patients (59.7%) achieved excellent clearance, 32 patients (21.4%) achieved good-moderate clearance, 19 patients (12.7%) obtained slight clearance, and 9 subjects (6.1%) had low or no removal of their lesion. In all cases, FPDL was found to be a safe and effective treatment for the abovementioned dermatological lesions in which skin microvessels play a role in pathogenesis or development. Further and single-indication studies, however, are required to assess a standardized and reproducible method for applying this technology to “off-label” indications.

Cost-efficacy analysis of 3% diclofenac sodium, ingenol mebutate, and 3.75% imiquimod in the treatment of actinic keratosis:

Actinic keratosis (AK) is a clinical condition characterized by keratinocytic dysplastic lesions of the epidermis, affecting individuals chronically exposed to sunlight. Topical therapies allow the treatment of a whole area of affected skin and currently include diclofenac sodium gel, 5-fluorouracil cream, 5-fluorouracil and acetylsalicylic acid solution, imiquimod cream, and ingenol mebutate gel. Due to the comparable efficacy of 3% diclofenac, ingenol mebutate, and 3.75% imiquimod in treating AK multiple lesions, a pharmacoeconomic evaluation of cost-effectiveness of the three treatments was needed. A cost-efficacy analysis comparing 3% diclofenac sodium with ingenol mebutate and 3.75% imiquimod was performed. In this analysis, efficacy data were combined with quality-of-life measurement derived from previous studies as well as the costs associated with the management of these lesions in Italy. Patients’ demographics and clinical characteristics were assumed to reflect those from the clinical studies considered.

Update of calcineurin inhibitors to treat inverse psoriasis: A systematic review

Inverse psoriasis commonly involves skin fold areas including the axillae, perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and retroauricular folds. Topical calcineurin inhibitors are indicated for the treatment of atopic dermatitis but have also been studied in the treatment of psoriasis. The object of the present study is to define the efficacy of topical calcineurin inhibitors in the treatment of psoriasis. We checked for English‐vernacular articles conveyed since 1990 in PubMed, Ovid/Cochrane, and Embase using “tacrolimus,” “pimecrolimus,” or “topical calcineurin inhibitors,” and “psoriasis” as keywords. Eight double‐blind studies and seven open studies displayed the ampleness of topical tacrolimus in psoriasis. Included studies demonstrated a considerable efficacy of topical administration of tacrolimus and pimecrolimus in the treatment of psoriasis, especially for facial, genital, and intertriginous areas. The role of topical tacrolimus and pimecrolimus in the treatment of psoriasis seems to be promising as shown by the results of double‐blind and open studies. Because these agents do not cause cutaneous atrophy, they have a special role in facial, genital, and intertriginous psoriatic lesions. Both agents await additional investigation to determine their roles.

Superiority of a vitamin B12-containing emollient compared to a standard emollient in the maintenance treatment of mild-to-moderate plaque psoriasis

Psoriasis is a chronic inflammatory skin disease affecting 2%–3% of the population. The wide range of drugs currently available for its treatment could be associated, in the long term, with organ toxicity and adverse events, thus, clinical monitoring throughout treatment is required. This investigator-initiated trial (IIT) evaluated the efficacy and the safety of a vitamin B12-containing ointment in comparison with glycerol-petrolatum-based emollient cream used twice a day to treat mild-to-moderate plaque psoriasis for a period over 12 weeks followed by a wash-out observation period of 4 weeks. This study was conducted as a randomized, controlled, single-blind, intra-patient left- to right-side trial comparing the efficacy and safety of vitamin B12-containing ointment (M-treatment) with a glycerol-petrolatum-based emollient cream (C-treatment). The Psoriasis Area Severity Index (PASI) was determined at baseline (T0), at time points T2 (14 days), T4 (4 weeks), T8 (8 weeks), T12 (12 weeks) and 4 weeks after the end of the wash-out period (F1). In total, 24 patients with plaque psoriasis were randomized to receive left- or right-side treatment with B12 ointment. From time point T2 to time point F1, there was a statistically significant difference in PASI reduction between M-treatment side and C-treatment side. At time point T 12, the difference between the mean reductions from baseline PASI scores by 5.92 ± 2.49 (87, 6%) in the M-treatment side versus 1.08 ± 1.02 (23, 1%) C-treatment side was statistically highly significant (PWex < 0.001). On the contemporary panorama in the treatment of psoriasis, we conclude that vitamin B12 ointment will represent a new concrete therapy option and should be considered in the update of therapeutic algorithm for the treatment of psoriasis

Ablative fractional laser improves treatment of actinic keratoses with Ingenol Mebutate

Actinic keratoses (AK) are pre-neoplastic lesions related to an excessive ultraviolet exposure that represent an emerging issue in the area of skin diseases which undergo high risk for developing squamous cell carcinoma (SCC). In this open study, we tested the safety efficacy profile of sequential ablative laser and Ingenol Mebutate gel (IngMeb). Thirteen patients with a total of 99 lesions were selected for this open study. When multiple lesions on the same area were found, the treatment area was split in half. In one group, fractional CO2 laser microablative treatment was performed the day before three daily applications of IngMeb 150 lg/g; the other group received IngMeb without previous laser ablation. Fifty-six lesions were treated with laser and IngMeb and a total of 43 lesions in the second group were treated with IngMeb alone. Results at the 12-week follow-up visit showed that a clearance rate of 50/56 (89.2%) had been achieved. On the side that was not pre-treated with laser, 31 out of 43 lesions were cleared (72.1%). In our opinion, ablative fractional laser treatment could improve topical treatment of AKs, or provide a further therapeutic option for resistant patients.