Down syndrome and biological treatments in dermatology: Efficacy and safety in our real-life experience and review of literature.

Down syndrome (DS) is the most common chromosomal disorder; several dermatological conditions are common in these patients; among them, psoriasis and atopic dermatitis can be frequently encountered. From 2017 to today, we retrospectively identified 4 adults and 3 under 18-year-old patients treated with biological drugs, from our research database. The first endpoint of this study was to evaluate whether the biological drugs work in these special population, and a secondary endpoint was to evaluate any loss of efficacy or any side effects during follow-up. All patients were treated with biological drugs experience resolution of their psoriasis. Mean PASI (Psoriasis Area Severity Index), BSA (Body Surface Area) and DLQI (Dermatology Life Quality Index) at baseline were 20, 16.5 and 25. At week 4, mean PASI, BSA and DLQI decreased, respectively, to 8, 6 and 12, while at week 24, mean values were, respectively, 3, 1.3 and 1. The patients that started therapy earlier, at week 52, do not have signs of recurrence and side effects. We highlighted that no official guidelines exist to approach these patients, from a literature evaluation the most employed drugs are anti-TNFα and in particular adalimumab. In our experience, the new anti-interleukin drugs seem to be well-tolerated, with no sides effect, good compliance and no loss of efficacy.

Is Apremilast a Safe Option in Patients with History of Melanoma? A Case Series and a Review of the Literature.

Background: Recently it has been reported that apremilast might promote melanogenesis and it would therefore not be safe to use this drug in patients with psoriasis who have a history of melanoma. Methods: From January 2017 to December 2020, we retrospectively identified, within a cohort of 635 patients in follow-up care for melanoma, 16 cases of patients with psoriasis treated with apremilast and history of melanoma. Patients were monitored at our unit for a mean duration of 36 months of follow up. Results: The use of apremilast, in our case series was, thus, effective in managing psoriasis without causing recurrence of previous melanoma or any new suspicious lesions which would need removal. Discussion: It has been speculated that apremilast might not be safe in patients who have a history of melanoma as it would be involved in the stimulation of melanogenesis and consequent possibility of recurrence of previous melanoma. Conclusion: Our data show that none of the patients treated with apremilast developed recurrence of melanoma at 36 months of follow-up. Further studies are necessary to confirm the safety of apremilast in a larger number of patients with concurrent malignancies, specifically melanoma, and for a longer follow-up period.

Topical and Conventional Systemic Treatments in Atopic Dermatitis: Have They Gone Out of Fashion?

Atopic dermatitis is a Th2 disease, due to relapse of IL-4 and IL-13 by Th2 cells. Despite the approval by FDA of dupilumab, the first monoclonal antibody for the severe forms, traditional drugs remain a milestone for the treatment of this dermatosis. Dermatologists need a good knowledge of all therapies for an integrated and personalized management of patients.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

CMV Infection: A Clinical Challenge in Biological Therapy? The Case of Asymptomatic Patients with Persistent Positive Immunoglobulin M Anti-CMV Treated with Secukinumab.

The use of biological therapy is now common practice in the treatment of immune-mediated inflammatory diseases (IMID). Currently, there are no guidelines related to the management of cytomegalovirus (CMV) infections or reactivation during therapy with biological agents. Furthermore, there is a lack of guidance on the management of asymptomatic patients with persistent positive immunoglobulin (Ig)M anti-CMV after an extended period and who have to undergo therapy with biological agents. We report the case of a patient in this situation for whom treatment with biological drugs for psoriasis was indicated. A good clinical response was obtained with secukinumab and maintained during 6 months of follow-up. No infectious disease or reactivation of CMV infection occurred. We suggest some possible guidelines for the management of such cases.