Piergiacomo Calzavara Pinton

Cost-effectiveness analysis of TNF-α blockers for the treatment of chronic plaque psoriasis in the perspective of the Italian health-care system

The cost‐effectiveness of biological treatments for psoriasis is not well determined and may vary from country to country. The objectives of this study was to perform a cost‐effectiveness analysis of infliximab compared with other anti‐tumor necrosis factor‐α agents for the treatment of psoriasis in Italy. The incremental cost‐effectiveness ratio per patients achieving at least 75% improvement in the psoriasis area and severity index assessed over 24‐ and 48–50‐week periods was calculated. Efficacy data were drawn from randomized controlled trials when available or from open label studies. Considering patients achieving psoriasis area and severity index at week 24 and 48–50, infliximab was dominant (more effective and less costly) over etanercept given at 50 mg twice weekly. In contrast, infliximab was not dominant over etanercept at other dosages or over adalimumab. When considering the impact of therapy on quality of life at Week 12 using the Dermatology Life Quality Index equal to zero, infliximab resulted more effective and less costly than etanercept. Therefore, infliximab seems to be cost‐effective in the therapy of psoriasis. Further cost‐efficacy evaluations based on head‐to‐head trials are necessary to address health economic considerations.

Differential management of mild-to-severe psoriasis with biologic drugs: An Italian Delphi consensus expert panel

Abstract Background: In the management of moderate-to-severe psoriasis, increasingly complex clinical scenarios necessitate practical tools for appropriate biologic therapy selection in individual patients. An Italian Delphi consensus panel provided guidance on biologic use in selected clinical scenarios. Methods: Ten experts defined statements under consideration, which were distributed as an online survey to a dermatologist panel. Plenary discussions of contentious statements were held to achieve consensus. Results: The survey was sent to 30 clinicians. After plenary discussions, consensus was reached on all 20 statements on the following topics: special populations; infections; comorbidities; immunogenicity; extra-cutaneous involvement; pregnancy; and adherence. Three statements required further discussion in order to gain consensus: use of subcutaneous biologics in mild liver impairment (final 94% agreement), use of any biologic in discoid lupus erythematosus (final 100% disagreement), and use of etanercept in patients with history of hypersensitivity reactions to drugs and/or food (final 75% disagreement). Conclusions: This Delphi expert consensus on the use of biologics in psoriasis provides practical recommendations for dermatologists to use when choosing an appropriate biologic in challenging but common clinical scenarios. More data are required to clarify clinical differences of biologic drugs used to treat psoriasis.

Treatment patterns with systemic antipsoriatic agents in childhood psoriasis: an Italian database analysis

BACKGROUND The majority of available systemic therapies have never been systematically investigated in moderate to severe childhood plaque psoriasis. For this reason, treatment preferences for moderate to severe psoriasis in childhood are still unknown. The aim of this study was to investigate the systemic treatment patterns of moderate to severe psoriasis in children and adolescents aged 18 or older in Italy. Additional secondary outcomes were duration of treatment and reasons for discontinuation. METHODS In order to define differences in treatment patterns, we performed a chart review of all consecutive patients treated with systemic drugs during an index period of 5 years. Consecutive sampling of all patients with psoriasis aged ≤18 years, who had been treated with at least one systemic drug over a 5-year period, was made. RESULTS The records of 58 consecutive patients, 27 males, 31 females. with moderate to severe psoriasis treated with at least one systemic therapy were reviewed. The median age (standard deviation) at the start of the first systemic treatment was 11.7±3.7 years. The most preferred first-line systemic treatment was cyclosporine, which was administered as first systemic treatment in 53.4% of patients, followed by acitretin in 22.4% of patients, etanercept and PUVA respectively in 8.6%, methotrexate in 6.8%. 48.2% of patients received a second systemic treatment due to inefficacy or side effects of the first-line therapy during the index period. Because of the small sample, and voluntary contribution, selection bias may have occurred. CONCLUSIONS A considerable variation in the management of the first-line systemic therapy in children with moderate to severe psoriasis was observed. Cyclosporine was most commonly preferred as a first-line treatment. The availability of new therapeutic agents could change the scenario of treatment patterns in childhood psoriasis.

Plasma levels of polychlorinated biphenyls and risk of cutaneous malignant melanoma: A hospital-based case-control study

Polychlorinated biphenyls (PCB) have been classified by the International Agency for Research on Cancer (IARC) in Group 1 as carcinogenic to human, based on sufficient evidence in humans of an increased risk of cutaneous malignant melanoma (CMM), however few studies have been done in the general population. This study examined the relationship between PCB plasma levels and risk of CMM adjusting for sun sensitivity and sun exposure in a province of Northern Italy (Brescia), where a chemical factory produced PCBs from 1938 to 1984 causing human contamination. A case-control study of 205 CMM patients and 205 control subjects was conducted. Cases and controls were assayed for plasma levels of 33 PCB congeners. No associations was found between risk of CMM and plasma levels of total PCB (OR = 0.81; 95% CI: 0.34-1.96 for highest vs lowest quartile) or specific congeners. The study confirmed the association with light skin colour (OR = 3.00; 95% CI: 1.91-4.73), cumulative lifetime UV exposure (OR = 2.56; 95% CI: 1.35-4.85) and high level of education (OR = 1.45; 95% CI: 1.03-2.05). This case-control study does not support the hypothesis of an association between current plasma levels of PCBs and CMM development in the general population.

Pseudolymphoma tattoo-induced

Tattooing has become more and more popular in today’s society. The most common dermatological tattoo complications are represented by hypersensitivity reaction to tattoo pigments like irritant and allergical contact dermatitis, development of lichenoid areas and granulomatous responses, such as sarcoid granulomas or foreign body granulomas. Less frequently patients developing discoid lupus erythematous have been reported. Pseudolymphoma is an uncommon reactive lymphocytic proliferation mimicking the histological and clinical features of a malignant skin lymphoma. We herein report a pseuldoymphoma limited to the red area of a multicolour tattoo of the leg.

Serum levels of tumor necrosis factor-alpha in patients with psoriasis before, during and after narrow-band UVB phototherapy

BACKGROUND Narrow-band UVB (NB-UVB) phototherapy is widely used worldwide for moderate and severe psoriasis, which is a chronic autoimmune inflammatory disease characterized by skin infiltrates of Th1-, Th17- and Th22-cells releasing locally pro-inflammatory cytokines. We investigate serum levels of tumor necrosis factor-α (TNF-α) in psoriatic patients before and after NB-UVB phototherapy. METHODS Twenty-eight subjects with moderate/severe plaque type psoriasis were enrolled. The severity of skin involvement was rated according to the Psoriasis Area and Severity Index (PASI) score at baseline (T0) and after 4 (T1) and 12 (T2) weeks of NB-UVB treatment. At the same time points, blood samples were taken for evaluation of TNF-α levels. NB-UVB phototherapy was administered twice weekly on non-consecutive days until 12 weeks. RESULTS The median PASI score significantly decreased from 12.0 at baseline (T0), to 6.9 after 4 weeks (T1, P<0.001) and to 0 after 12 weeks (T2, P<0.001). TNF-a serum levels significantly increased in respect to the baseline after 12 weeks of therapy. CONCLUSIONS NB-UVB phototherapy is highly effective against psoriasis but, as it increases the TNF-α serum level, it seems unlikely that it can decrease the chronic inflammatory state that is thought to be responsible of the systemic co-morbidities of psoriasis.

Reply to Scalone and Cortesi: “Cost-Utility Analysis of Biologic Therapies to Treat Chronic Plaque Psoriasis in Italy: The Importance of Using Updated and Adequate Social Tariffs to Calculate QALYs”

Scalone and Cortesi [1] point out that our paper does not mention the social tariffs used to convert EQ-5D-3L into quality-adjusted life-years (QALYs). The answer is straightforward: we applied the UK social tariffs—those most employed in Italy at the time of our research. Indeed, just a few months before our paper was published, Scalone et al. [2] published new tariffs, specific for Italy, but our elaborations had already been finalized when their paper was published. The subject of transferability is of great interest, and consequently it would seem worthwhile to provide a few more comments. In the first place, having a specific algorithm for Italy is undoubtedly very important; it is also certainly desirable that this be referred to in the future for that which regards work carried out for the Italian population. But, in the specific case of our paper, the aim was not so much to calculate the value of the cost per QALY of treatments for the purpose of reimbursement decisions, as whether or not to confirm the results of the pivotal trials in real practice. Our results may obviously be relevant to public authorities in terms of organization of assistance in addition to (and perhaps more than) terms of pricing/reimbursement. It is from this retrospective viewpoint that we believe that use of the new social tariffs would establish a bias in the comparison; in fact, most of the previous studies used the UK social tariffs. Coming back to the prospective impact of the new evidence provided by Scalone et al. [2], obviously in the presence of analysis aimed at making prospective decisions regarding public reimbursement for a certain treatment, the use of country-specific data regarding the population being

Echocardiographic evaluation of diastolic dysfunction in young and healthy patients with psoriasis: A case-control study

Psoriasis is a systemic inflammatory disease with a great prevalence in general population. The inappropriate activation of the cellular immune system has been hypothesized to be an independent cardiovascular risk factor, given the higher incidence of cardiovascular disorders in psoriatic patients. Echocardiographic abnormalities have been demonstrated too: the aim of our study was to evaluate the presence of preclinical cardiac dysfunction in a cohort of psoriatic patients without cardiovascular risk factors. We enrolled 52 patients with the diagnosis of chronic plaque psoriasis, compared with a control group not affected by any relevant systemic diseases and inflammatory disorders. In all patients and control group, echocardiographic conventional and tissue Doppler (TDI) studies were conducted. The analysis of echocardiographic parameters revealed normal dimension, mass and systolic function of the left ventricle. Left ventricular diastolic dysfunction was found in 36.5% patients in the psoriasis group versus 0% in control group, and significant reduction of the E/A ratio was found also for the right ventricle. A significant increase of mitral regurgitation has been found in psoriatic patients (p=0.005). The early recognition of cardiovascular pre-clinic disease in psoriatic patients may guide a strict follow up and an early treatment, potentially improving cardiovascular prognosis.

Back to the future: a new topical approach for mild-to-moderate psoriasis

Psoriasis is a chronic-relapsing skin disorder which requires long-term treatments. Therapeutic options for psoriasis include topical treatments, phototherapy and systemic therapy. However, those treatments, and particularly the topical drug therapies, may present some limitations, including poor efficacy/tolerability ratio and lack of adherence. Recently, the supersaturated aerosol foam formulation of the fixed combination calcipotriene plus betamethasone dipropionate (Cal/BD) has gained major attention because it overcomes some of the limitations associated with other topical treatments. This fixed-combination has increased efficacy compared with its individual components. Moreover, the alcohol-free aerosol foam formulation allows a higher penetration of the active ingredients into the skin, resulting in enhanced bioavailability and, consequently, in better clinical outcomes than other products with the same components. Given the short duration of therapy course and the fast onset of action, a reduced amount of Cal/BD foam formulation would be required for the treatment of psoriasis patients, resulting also in cost saving. Therefore this novel formulation could represent an alternative to other topical agents and a first-line therapy in the treatment of mild and mild-to-moderate psoriasis.

Letter: Onychocryptosis of the Toenail: The Effectiveness of Surgical Matricectomy

The detection system used to measure bubble sizes was calibrated to convert pixel coordinates to actual coordinates. Each pixel of the camera corresponds to 1.08 lm. The smallest bubbles analyzed had a size of about 10 pixels in diameter to assure sufficient accuracy (the error in each diameter is ~1 lm). In each picture, approximately 300 bubbles were analyzed in a semi-automated manner, taking advantage of the clear image of the diffraction line as indicated in Figure 3 to improve accuracy. The bubbles appeared in the first layers adjacent to the observation window of the sample holder. As explained in the original study, the sample height was 7 mm. The foam was freshly generated using the Tessari method, indicating that the foam had a homogeneous composition before it was emptied into the sample holder. When timedependent degradation was studied, two procedures were followed; the foam was kept in the 7-mm-high test sample (Figure 6), and the syringe was placed horizontally to avoid only the bottom part of its deteriorated content being examined (Figure 5), which explains the difference between Figures 5 and 6. Bubble size distribution was measured as a laboratory experiment to determine whether this essential characteristic of foam affects the stability and rheological properties of foam and