Use of biological drugs in patients with psoriasis and psoriatic arthritis in Italy: Results from the PSONG survey.

This Italian multicenter retrospective study compared the drug survival and efficacy of different anti-TNF agents in psoriasis (PsO) and psoriatic arthritis (PsA) patients. A database of PsO/PsA patients treated with adalimumab, etanercept, and infliximab from May 2013 to May 2014 was analyzed. PASI 75, 90, and 100 was calculated at each time point to evaluate efficacy. Drug survival rate and probability of maintaining PASI response were evaluated. The impact of dependent variables on probability of PASI 75 loss was evaluated by logistic regression. 1,235 patients were included, 577 with PsO and 658 with PsA. Highest survival rates were observed with adalimumab followed by etanercept and infliximab in PsO and PsA patients. The probability of maintaining PASI response was significantly higher for adalimumab followed by infliximab. For PsO patients, the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 8.1; 95% CI: 4.2-15.6, p < .001) or infliximab (OR: 6.6; 95% CI: 2.6-16.3, p < .001) vs. adalimumab. Likewise, for PsA patients the odds of losing PASI 75 was higher in etanercept-treated patients (OR: 2.3; 95% CI: 1.4-3.8, p = .01) or infliximab (OR: 2.2; 95% CI: 1.1-4.1, p = .018) vs. adalimumab. Adalimumab could be the best therapeutic option over other anti-TNF agents for the treatment of PsO and PsA patients.

The GENDER ATTENTION Observational Study: Gender and Hormonal Status Differences in the Incidence of Adverse Events During Cyclosporine Treatment in Psoriatic Patients.

INTRODUCTION: Female sex has been shown to be a risk factor for the development of adverse drug reactions; however, this has not been studied for cyclosporine (CsA). The aim of this study was to investigate, in Italian dermatological practice, the influence of gender and menopause and related hormones on the incidence of adverse events (AEs) during CsA treatment in psoriatic patients. METHODS: Multicenter, prospective, observational study conducted from May 2011 to June 2013. Patients with plaque psoriasis, undergoing a new CsA administration course, or about to start it, were enrolled in the outpatient clinics of Italian dermatological centers. During the 2-6 months of study duration, patients had to note all AEs that occurred in a diary that was reviewed by the investigators at the follow-up visit. Sex hormone levels were measured within 7 days from the start date of a menstrual cycle. RESULTS: A total of 969 adult psoriatic patients were enrolled in the study, divided into four cohorts: fertile women and corresponding age-matched men; postmenopausal women and corresponding age-matched men. A significant difference in the percentage of patients with AEs was observed between fertile and postmenopausal women, but not between women and age-matched men. AE incidence rate was about 37% higher in fertile women than in age-matched men and about 18% higher in postmenopausal women than in age-matched men, but differences were not statistically significant. Incidence rate ratio of fertile vs. postmenopausal women was 0.67, reaching statistical significance. AEs were mild or moderate in severity in the great majority of patients of all cohorts and postmenopausal women had significantly less grade 1-2 AEs compared to fertile women, but more grade 3-4 AEs. FSH levels were significantly higher in postmenopausal women reporting no AEs, and DHEA sulfate levels were about 10% higher in men with no AEs, compared to those reporting at least one AE. Cortisol levels were slightly though significantly higher in postmenopausal women with no AE. CONCLUSIONS: A better understanding of sex- and hormone-related influences on drug responses may help to improve drug safety and efficacy, by permitting one to tailor pharmacological treatments to individual subjects or defined patient cohorts. FUNDING: Novartis Farma S.p.A., Italy.

The nitrobenzoxadiazole derivative MC3181 blocks melanoma invasion and metastasis.

The novel nitrobenzoxadiazole (NBD) derivative MC3181 is endowed with remarkable therapeutic activity in mice bearing both sensitive and vemurafenib-resistant human melanoma xenografts. Here, we report that subtoxic concentrations of this compound significantly reduced invasiveness of BRAF-V600D mutated WM115 and WM266.4 melanoma cell lines derived from the primary lesion and related skin metastasis of the same patient, respectively. The strong antimetastatic activity of MC3181 was observed in both 2D monolayer cultures and 3D multicellular tumor spheroids, and confirmed in vivo by the significant decrease in the number of B16-F10 melanoma lung metastases in drug-treated mice. Our data also show that MC3181 affects the lactate production in the high glycolytic WM266.4 cell line. To unveil the MC3181 mechanism of action, we analyzed the ability of MC3181 to affect the degree of activation of different MAPK pathways, as well as the expression/activity levels of several proteins involved in angiogenesis, invasion, and survival (i.e. AP2, MCAM/MUC18, N-cadherin, VEGF and MMP-2). Our data disclosed both a decrease of the phospho-active form of JNK and an increased expression of the transcription factor AP2, events that occur in the very early phase of drug treatment and may be responsible of the antimetastatic effects of MC3181.

Efficacy of cyclosporine A as monotherapy in patients with psoriatic arthritis: a subgroup analysis of the SYNERGY Study.

BACKGROUND: The SYNERGY Study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNERGY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. METHODS: Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. RESULTS: Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexes of cutaneous and spinal involvement, PASI and BASDAI were significantly reduced over the study period, as were the number of swollen and tender peripheral joints, and enthesitis and dactylitis. CONCLUSIONS: Cyclosporine in monotherapy confirmed its efficacy in cutaneous psoriasis and suggested to be effective also on PsA, reducing spinal and peripheral joints' signs and symptoms.

New therapeutic approaches in the treatment of anogenital lichen sclerosus: does photodynamic therapy represent a novel option?

BACKGROUND: Lichen sclerosus et atrophicus (LSA) is an inflammatory, mucocutaneous disorder that affects male and especially female with a debilitating impact on the quality of life. Common localization is the anogenital area. If not treated LSA can leave scars, functional impairment and can evolve in squamous cell carcinoma. The first line of treatment is represented by topical, ultra-potent corticosteroids, but often patients are unresponsive; moreover this therapy is frequently associated to relapses of the disease after discontinuation. METHODS: In this prospective observational study, the efficacy of three different treatments - topical calcineurin inhibitors, avocado and soya beans extracts, and methyl aminolevulinate photodynamic therapy (MAL-PDT) - was evaluated, and an effort has been made to define a therapeutic algorithm according to the severity of the disease. RESULTS: Of the 150 patients who were referred to the outpatient clinic for a dermatological and gynecological visit, 33 met the inclusion criteria. Sixteen (88%) patients showed an improvement of the lesion and a reduction of the itch; 3 (16.7%) patients with sever itch and fissurated lesions were evaluated for the MAL-PDT therapy. A total of 9 patients, after accurate examination of the lesions, were treated with MAL-PDT. The totality of the patients experienced a resolution of the lesions. CONCLUSIONS: In the early stages the use of ASE can represent a valid alternative that is well tolerated by the patients reducing the itching, dryness and improving the mucosal texture. The use of MAL-PDT represents a valid treatment in the moderate-severe stages of LSA.

Atopic dermatitis and dental manifestations.

BACKGROUND: Atopic dermatitis is a chronic skin disease associated with epidermal dysfunction commonly seen in children. The aim of this study was to evaluate the possible correlation between atopic dermatitis and dental diseases in paediatric patients. METHODS: An observational study was conducted by the Department of Paediatric Dentistry of the Policlinico Tor Vergata among a group of 300 children, between 2 and 17 years of age and of both genders, for a period of 6 months from January 2013 to June 2013. Socio-demographic data including race, gender, and age were collected. Clinical and dermatological examinations were performed in all patients; family and medical history of atopy was recorded for each patient and relatives. RESULTS: Three hundred patients, aged between 2 and 17 years, with mean age of 8.9 (±2.12), were enrolled; 90/300 (30%) were affected by atopic dermatitis. Of those, 69/90 (76.6%) had a medical history of spoil habit, 49/90 (54%) had caries, 58/90 (64.4%) had malocclusion disease, 13/90 (14.4%) had anatomical dental abnormalities. CONCLUSIONS: In conclusion, in the current investigation we found a higher prevalence of atopic dermatitis in pediatric dentistry patients compared to the general population suggesting that dental diseases could be involved in the pathogenesis of AD.

Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics.

Actinic keratosis (AK) is a common keratinocyte intra-epidermal neoplasia. To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

Influence of body mass index and weight on etanercept efficacy in patients with psoriasis: A retrospective study.

AIM: To investigate the role of body mass index (BMI) and weight in the long-term efficacy of etanercept in patients with psoriasis. METHODS: Medical records were retrospectively analysed. Extracted data included weight, BMI, comorbidities and psoriasis area severity index (PASI). Patients were stratified by weight (<80 kg or ≥80 kg) and BMI (healthy, BMI 22 - 24.99 kg/m2; overweight, BMI 25 - 29.99 kg/m2; obese, BMI ≥30 kg/m2). RESULTS: The study included 66 patients. Body weight had no effect on etanercept efficacy. There was a significant reduction in etanercept efficacy in obese patients (n = 12) compared with healthy weight (n = 33) or overweight (n = 21) patients. CONCLUSION: Obesity has a negative effect on the efficacy of etanercept in psoriasis.

From patients' needs to treatment outcomes in psoriasis: Results from the 'pSORRIDI' experience.

OBJECTIVE: To evaluate results of the 'pSORRIDI' experience (which is a prevention campaign to evaluate the prevalence of comorbidities, multidisciplinary needs and appropriateness of the therapeutic approach for comorbidities) in patients already being treated for psoriasis. METHODS: Telephone interviews were conducted in patients with psoriasis, who then underwent comprehensive evaluation and investigation of comorbidities. If necessary, patients were referred to specialist cardiology, endocrinology and/or rheumatology services. RESULTS: Overall, 72.0% (54/75) of patients required a multidisciplinary consultation. Among patients referred to cardiology, therapeutic adjustment was needed in 33.3% (five of 15) patients and a redefined diagnosis in 26.7% (four of 15) cases. Among patients undergoing endocrinology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 61.1% (11/18) and 33.3% (six of 18) patients, respectively; for rheumatology evaluations, therapeutic adjustment and a redefined diagnosis were needed in 76.2% (16/21) and 19.0% (four of 21) of patients, respectively. CONCLUSIONS: Among patients with psoriasis, there may be a need for an improvement in the diagnosis of underlying comorbid conditions, and in disease management of both psoriasis and any comorbid conditions.

Combination therapy with etanercept in psoriasis: Retrospective analysis of efficacy and safety outcomes from real-life practice.

OBJECTIVE: To investigate the efficacy and safety outcomes of combination therapy used to optimize etanercept treatment in patients with psoriasis treated in real-life clinical practice. METHODS: Data from patients presenting with psoriasis, treated initially with etanercept monotherapy, were analysed retrospectively. Patients subsequently treated with combination therapy were further analysed. The Psoriasis Area and Severity Index (PASI) score was recorded for all patients receiving comedication; a subjective pain score was recorded in those with psoriatic arthritis receiving comedication after 12, 24 and 48 weeks' treatment and thereafter at 6-month intervals. RESULTS: From the database of 400 patients treated with etanercept, 37 patients (18 male; 19 female; mean age 59.43 years) underwent combination therapy due to lack of efficacy. Patients received mostly short-term (range 4-34 weeks) comedication with corticosteroids, cyclosporine, methotrexate, nonsteroidal anti-inflammatory drugs, acitretin or sulphasalazine. There were significant reductions in the mean PASI score from baseline at all timepoints. There were also significant reductions in the mean pain VAS score from baseline at all timepoints in patients with psoriatic arthritis. The drug survival rate was 59.6% over a mean duration of 323 weeks of etanercept treatment. The safety profile of combination therapy was satisfactory. CONCLUSIONS: Short-term comedication in combination with etanercept may optimize treatment options and improve long-term drug survival in patients with psoriasis.

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

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.

Small molecules and antibodies for the treatment of psoriasis: a patent review (2010-2015).

INTRODUCTION: Psoriasis is a chronic condition whose therapeutic armamentarium is increasingly being discussed, particularly when compared to past decades. The use of biologic agents has profoundly changed the history of this disease, as well as the management of psoriatic patients. Due to the enormous interest in psoriasis, as demonstrated within the scientific community and pharmaceuticals, new therapeutic targets have been identified and novel patented therapeutics are being tested. AREAS COVERED: This review sought to give an overview of small molecules and antibodies patented in the last five years for the treatment of psoriasis. Therapeutic agents either in the early or advanced phase of development have been described, primarily based on a systematic search using the PubMed Medline database. EXPERT OPINION: Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm.

Long-term use of a new topical formulation containing piroxicam 0.8% and sunscreen: efficacy and tolerability on actinic keratosis. A proof of concept study.

INTRODUCTION: Cyclooxygenase (COX) 1 and 2 enzyme up-regulation is involved in the pathogenetic process of actinic keratosis (A.K.) and non-melanoma skin cancers. Diclofenac, a non-steroidal anti-inflammatory (N.S.A.I.D.) drug, is used as topical treatment of A.K. Piroxicam is a N.S.A.I.D. characterized by a high COX-1 inhibition activity. STUDY AIM: We conducted an 18 month exploratory open-label study on A.K., to assess the efficacy and tolerability of a new topical formulation of piroxicam and sunscreen in A.K. PATIENTS: Enrolled subjects applied a galenic formulation of piroxicam 0.8%, vehiculated in a topical product containing sun filters with high (50+) and broad spectrum (UVA) actions, twice a day for 6 months. Subjects were then followed up for additional 12 months. Thirty-eight subjects with a total of 69 A.K. lesions participated in the trial. The primary outcome was the evolution of the Actinic Keratosis Erythema Scale Atrophy (A.K.E.S.A) score assessing erythema, scale, and atrophy of a target A.K. lesion. Secondary outcomes were the percentage of treated lesions with complete (100%) or partial (≥75%) clearance and the evaluation skin tolerability. RESULTS: A.K.E.S.A. mean (S.D.) score at baseline was 7.5 (1.2). After 6 months of treatment, A.K.E.S.A. score decreased to 0.9 (1.1), a -88% reduction versus baseline. At the end of follow-up, A.K.E.S.A. score was 0.8 (1.2). A complete response was achieved in 38 of the 69 lesions (55%, 95% C.I.: 43% to 66%) and clearance was maintained 1 year post-treatment. A partial clearance was observed in 57 of 69 treated lesions (83%, 95% C.I.: 73% to 91%). Adverse events were limited to mild local irritation. CONCLUSION: Our experience suggests that 6 month topical piroxicam 0.8% is efficacious and well tolerated in A.K. Clinical efficacy is maintained 1 year post-treatment. The main limitation of our study is that it was an open label non-controlled trial. Future controlled trials are warranted in order to compare the efficacy and tolerability of this topical piroxicam preparation with standard treatments in the management of A.K.

UVA1 Laser in the Treatment of Vitiligo.

OBJECTIVE: The purpose of this article was to evaluate the clinical efficacy and safety of a monochromatic 355 nm ultraviolet (UVA) laser in the treatment of vitiligo. BACKGROUND DATA: Broadband and narrow-band UV phototherapy has been proposed as an effective therapeutic option in vitiligo patients. METHODS: Seventeen consecutive, unselected patients (7 men and 10 women) were enrolled in an open-label, prospective study and treated twice weekly for 8 weeks at a fixed dose of 80-140 J/cm(2). Follow-up was 12 weeks. RESULTS: Clinical repigmentation was observed in 15/17 patients (88.23%), with limited side effects (mild post-treatment erythema and itching). Results were maintained during the 12 week phototherapy-free follow-up period. CONCLUSIONS: the present report suggests that UVA1 laser could be an applicable therapeutic option in patients with vitiligo.

Lack of efficacy of imiquimod in patients with basal cell carcinoma previously treated with rituximab for B cell lymphoma: two case reports.

BACKGROUND: Non-Hodgkin lymphomas are a heterogeneous group, which involve either B or T lymphocytes. The most used treatment is a chemotherapy regimen, which includes cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone combined with rituximab - a monoclonal antibody specific for CD20 - an antigen expressed on B lymphocyte membrane. Nonmelanoma skin cancers are the most common forms in patients who have lymphomas. CASE PRESENTATION: We reported the cases of two Caucasian men affected by non-Hodgkin disease, treated with chemotherapy and rituximab. After treatment, they both presented superficial basal cell carcinoma and we prescribed imiquimod 5 % cream. Unfortunately, the drug was not effective in either patient and the tumors were excised. CONCLUSIONS: We speculated about the effect of rituximab on B lymphocytes, on a particular population of T cells and on antigen-presenting dendritic cells that may have determined a lower expression of some surface antigens involved in antigen presentation. These cells are the specific targets of imiquimod to promote skin cancer cells apoptosis. A lack of action by imiquimod on skin cancer after treatment with rituximab is likely due to its transitory inhibitory effects on lymphocytes and Langherans cells. Further studies could be useful to understand the mechanism behind the lack of response.

Serum Protein Profile Changes in Psoriatic Patients Undergoing Treatment With Infliximab.

UNLABELLED: The therapeutic paradigm in psoriasis includes antitumor necrosis alpha agents that have been proved effective and safe as long-term therapy. Recently, it has been described a correlation between the use of biologic agents and the occurrence of monoclonal gammopathies, which are haematological conditions characterized by clonal plasma cells proliferation producing a monoclonal immunoglobulin that accumulates in the blood. OBJECTIVE: The aim of this study is to detect electrophoretic abnormalities in psoriatic patients undergoing treatment with infliximab. RESEARCH DESIGN AND METHODS: A retrospective study evaluating all charts from the clinic database of all patients treated with infliximab. The evaluation of serum protein profile is routinely performed in the clinical setting during biologic therapies. We reported the occurrence MGUS in infliximab-treated patients. RESULTS: The study analysis included 141 charts. Overall, 23 patients showed a MGUS in their electrophoretic profile, though in 6 cases MGUS was detected at the baseline. Thereby, 17 cases (12.06% of the study population) developed MGUS during infliximab therapy. CONCLUSIONS: Serum protein electrophoresis test represents a useful tool to detect and monitor any potentially harmful condition that could occur during treatment with a biologic agent. Particularly, it could be crucial for the detection of MGUS, which does not affect clinical response, and it does not represent a criteria to withdraw the treatment.

Rhodamine intense pulsed light versus conventional intense pulsed light for facial telangiectasias.

Facial telangiectasias represent the major aesthetic alterations of several chronic inflammatory disorders arising on facial skin. We herein report on relevant clinical results of a new subtype of intense pulsed light treatments, the so-called rhodamine intense pulsed light (r-IPL), in comparison with conventional IPL (c-IPL) treatments on forty-five patients affected by facial telangiectasias. The aim of this study is to determinate whether r-IPL represents an effective and safe treatment for the most common superficial vascular alterations and could be advised as a first choice therapy for facial telangiectasias.