Mapping exercise and status update of eight established registries within the TREatment of ATopic eczema Registry Taskforce.

BACKGROUND: The TREatment of ATopic eczema (TREAT) Registry Taskforce is a collaborative international network of registries collecting data of atopic eczema (AE) patients receiving systemic and phototherapy with the common goal to provide long-term real-world data on the effectiveness, safety and cost-effectiveness of therapies. A core dataset, consisting of domains and domain items with corresponding measurement instruments, has been developed to harmonize data collection. OBJECTIVES: We aimed to give an overview of the status and characteristics of the eight established TREAT registries, and to perform a mapping exercise to examine the degree of overlap and pooling ability between the national registry datasets. This will allow us to determine which research questions can be answered in the future by pooling data. METHODS: All eight registries were asked to share their dataset and information on the current status and characteristics. The overlap between the core dataset and each registry dataset was identified (according to the domains, domain items and measurement instruments of the TREAT core dataset). RESULTS AND CONCLUSIONS: A total of 4702 participants have been recruited in the eight registries as of 1st of May 2022. Of the 69 core dataset domain items, data pooling was possible for 69 domain item outcomes in TREAT NL (the Netherlands), 61 items in A-STAR (UK and Ireland), 38 items in TREATgermany (Germany), 36 items in FIRST (France), 33 items in AtopyReg (Italy), 29 items in Biobadatop (Spain), 28 items in SCRATCH (Denmark) and 20 items in SwedAD (Sweden). Pooled analyses across all registries can be performed on multiple important domain items, covering the main aims of analysing data on the (cost-)effectiveness and safety of AE therapies. These results will facilitate future comparative or joint analyses.

The impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biological therapies.

BACKGROUND: The beginning of 2020 has been marked by COVID-19 pandemic, with a strong impact on several national health systems worldwide. OBJECTIVE: To describe the impact of COVID-19 pandemic in a cohort of Italian psoriatic patients treated with biologics. METHODS: A telephone survey was conducted in May 4-10 2020 about the Italian lockdown period (March 9-May 3 2020) in a cohort of psoriatic patients treated with biologics, asking about any exposure to COVID-19, disease status, continuation of therapy, work activity and psychological status through Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale (PSS) and Brief Resilience Scale (BRS). RESULTS: 226 patients were interviewed, with no COVID-19 positive cases. Sixty-three of 226 (27.9%) described worsening of the disease with a correlation to drug withdrawal [43/226 (19%)]. Correlation was also found between the worsening of psoriasis and HADS anxiety, HADS depression, BRS and PSS abnormal scores considered both as categorical and continuous variables. No correlation was found between worsening of psoriasis and work activity. CONCLUSION: Uncertainty about whether biologics could increase the risk of SARS-CoV-2 infection led to drug withdrawal with subsequent worsening of psoriasis. Moreover, psychological status also had a direct influence on the clinical course of the disease.

Impact of Body Mass Index on the Efficacy of Biological Therapies in Patients with Psoriasis: A Real-World Study.

BACKGROUND: The efficacy of biological therapies used for the treatment of chronic plaque psoriasis can be influenced by numerous variables including  body mass index (BMI). OBJECTIVE: This study aimed to evaluate the impact of BMI on the short-term and long-term efficacy of biological therapies in clinical practice and to identify the best therapeutic options in obese patients (BMI ≥ 30 kg/m2). METHODS: A multicentric retrospective study was conducted in patients who initiated a biological therapy during the period January 2006-December 2019. The proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index at weeks 12 and 24 was calculated also recording the 12- and 24-month drug survival as a measure of long-term efficacy, performing multivariate analyses to assess the impact of different variables. RESULTS: Five hundred and four patients with psoriasis were included. After 12 and 24 weeks, the proportion of patients achieving a 90% improvement of baseline Psoriasis Area and Severity Index response was higher in patients with a BMI < 30 kg/m2 compared with those with a BMI ≥ 30 kg/m2 [54.90% vs 43.45% (p = 0.014) at week 12 and 66.84% vs 56.55% (p = 0.021) at week 24]. The Kaplan-Meier survival curves showed how obese patients had a higher probability of discontinuation due to a lack or loss of efficacy (p = 0.0192) compared with non-obese patients. The drug survival analysis also showed that BMI negatively affected the drug survival of secukinumab (odds ratio 1.27, p < 0.001) and ustekinumab (odds ratio 1.06, p = 0.050), while the long-term efficacy of adalimumab, etanercept, and ixekizumab was not influenced by BMI. CONCLUSIONS: Obesity (BMI ≥ 30 kg/m2) negatively affects the clinical response of biological drugs in psoriatic patients, with anti-interleukin drugs being more affected by BMI than anti-tumor necrosis factor drugs.

Management of patients with atopic dermatitis undergoing systemic therapy during COVID-19 pandemic in Italy: Data from the DA-COVID-19 registry.

BACKGROUND: Few and small studies have described the management of immunomodulant/immunosuppressive therapies or phototherapy in atopic dermatitis (AD) patients during coronavirus disease 2019 (COVID-19) pandemic. METHODS: A national registry, named DA-COVID-19 and involving 35 Italian dermatology units, was established in order to evaluate the impact of COVID-19 pandemic on the management of adult AD patients treated with systemic immunomodulant/immunosuppressive medications or phototherapy. Demographic and clinical data were obtained at different timepoints by teledermatology during COVID-19 pandemic, when regular visits were not allowed due to sanitary restrictions. Disease severity was assessed by both physician- and patient-reported assessment scores evaluating itch intensity, sleep disturbances, and AD severity. RESULTS: A total of 1831 patients were included, with 1580/1831 (86.3%) continuing therapy during pandemic. Most patients were treated with dupilumab (86.1%, 1576/1831) that was interrupted in only 9.9% (156/1576) of cases, while systemic immunosuppressive compounds were more frequently withdrawn. Treatment interruption was due to decision of the patient, general practitioner, or dermatologist in 39.9% (114/286), 5.6% (16/286), and 30.1% (86/286) of cases, respectively. Fear of increased susceptibility to SARS-CoV-2 infection (24.8%, 71/286) was one of the main causes of interruption. Sixteen patients (0.9%) resulted positive to SARS-CoV-2 infection; 3 of them (0.2%) were hospitalized but no cases of COVID-related death occurred. CONCLUSIONS: Most AD patients continued systemic treatments during COVID pandemic and lockdown period, without high impact on disease control, particularly dupilumab-treated patients.

Successful Combination of Systemic Agents for the Treatment of Atopic Dermatitis Resistant to Dupilumab Therapy.

BACKGROUND: Dupilumab, a monoclonal antibody inhibiting the signaling pathway of IL-4/IL-13, was shown to be safe and effective in the treatment of moderate/severe atopic dermatitis (AD) in several clinical trials and real-life experiences, with only a small percentage of patients showing to be resistant or to lose disease control. OBJECTIVES: In this study, we investigated the effectiveness and safety in combining dupilumab with systemic agents or phototherapy in patients experiencing an inadequate response to dupilumab. METHODS: This retrospective, monocentric, observational study consecutively included patients aged >18 years, with moderate-severe AD, under treatment with dupilumab. In this cohort of patients, we analyzed data of subjects who experienced an inadequate response to dupilumab, even when combined with topical corticosteroids, and for whom an additional systemic treatment or phototherapy was combined to dupilumab. RESULTS: In this study, we included a total population of 69 patients treated with dupilumab. In 12/69 patients (17.4%) showing an inadequate response to dupilumab, a combined treatment consisting of dupilumab plus methylprednisolone (n = 5), cyclosporine (n = 4), methotrexate (n = 2), or narrow band-UVB (n = 1) was administered. Overall, after 8 weeks of combined therapy, the majority of patients (11 of 12) obtained an improvement of signs and symptoms of AD. Patients treated with combined therapy did not experience any adverse events, neither did they withdraw treatment because of the occurrence of adverse events. CONCLUSIONS: This study suggests that the combination of dupilumab with a conventional drug or phototherapy may represent a valid therapeutic choice, maintaining a good safety profile in AD patients recalcitrant to dupilumab monotherapy.

Characteristic of chronic plaque psoriasis patients treated with biologics in Italy during the COVID-19 Pandemic: Risk analysis from the PSO-BIO-COVID observational study.

Background: The susceptibility of patients with chronic plaque psoriasis and the risks or benefits related to the use of biological therapies for COVID-19 are unknown. Few data about prevalence, clinical course and outcomes of COVID-19 among psoriatic patients were reported. The aims of this study were 1) to assess the prevalence and severity of COVID-19 in psoriatic patients treated with biologic agents during the first phase of the emergency (22 February to 22 April 2020) in Italy, and 2) to report the clinical outcomes of patients who have been exposed to individuals with confirmed SARS-CoV-2 infection. Methods: Patients with moderate-to-severe chronic plaque psoriasis, aged ≥18 years and undergoing treatment with biologic agents as of 22 February 2020, were eligible to be included in PSO-BIO-COVID study. Demographic and clinical characteristics of patients using any biologic for psoriasis treatment between 22 February and 22 April 2020 were registered. Results: A total of 12,807 psoriatic patients were included in the PSO-BIO-COVID study. In this cohort 26 patients (0.2%) had a swab confirmation of SARS-CoV-2 infection. Eleven patients required hospitalization and two died. Conclusion: The incidence of COVID-19 observed in our cohort of psoriatic patients (0.2%) is similar to that seen in the general population (0.31%) in Italy. However, the course of the disease was mild in most patients. Biological therapies may likely lessen 'cytokine storm' of COVID-19, which sometimes lead to multiple organ failure, ARDS, and death.

The pharmacological management of patients with comorbid psoriasis and obesity.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease that is increasingly being recognized as a complex disorder affecting multiple systems. Systemic inflammation is considered the pathogenic link between psoriasis and its comorbid conditions that include arthritis, metabolic disorders, depression, and cardiovascular diseases. The presence of comorbid conditions modifies both its clinical management and the therapeutic approach in psoriatic patients. AREAS COVERED: This review describes the clinical, epidemiological, and pathogenic link between psoriasis and obesity. Furthermore, data related to the effects of synthetic antipsoriatic drugs on obesity are collated. EXPERT OPINION: Obesity is one of the most common comorbid conditions that is relevant both for a patient's overall health and the clinical outcomes of antipsoriatic therapies. Indeed, some treatments of psoriasis might be impaired by adiposity. Moreover, obesity's association with dyslipidemia, hypertension, and increased liver enzymes could further be worsened by acitretin, cyclosporine and methotrexate, respectively. Therefore, the identification of therapeutic targets whose blockade could have positive effects on both psoriasis and mechanisms regulating body weight homeostasis may be of great relevance to the treatment of patients with psoriasis.

Optimizing Anti-Inflammatory and Immunomodulatory Effects of Corticosteroid and Vitamin D Analogue Fixed-Dose Combination Therapy.

Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed-dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed-dose combination therapy of corticosteroid and vitamin D analog and highlight the added potential of innovative drug delivery for the treatment of psoriasis. FUNDING: LEO Pharma.

Role of IL-23 in the pathogenesis of psoriasis: a novel potential therapeutic target?

INTRODUCTION: Psoriasis is a chronic inflammatory skin disorder determined by the activation of several immune cells and resident tissue cells. Various cytokines mediate inflammatory signals, including IL-23, which is an important factor involved in the differentiation of T helper (Th17) cells. AREAS COVERED: Increasing evidence suggests that IL-23 is a central cytokine to the pathogenesis of psoriasis. An overview on both experimental and human data will be reported in order to support the hypothesis of a key pathogenic role of IL-23/Th17 axis. EXPERT OPINION: Targeting IL-23 might be a more selective, valid and effective therapeutic approach, which, potentially, may show important advantages in terms of long-term efficacy and safety in the treatment of psoriasis.

New topical treatments for psoriasis.

INTRODUCTION: Psoriasis is a common immune-mediated disorder that in 70% of cases appears in mild or mild-to-moderate form. Psoriasis is usually treated with topical medications and/or phototherapy with variable efficacy in controlling the disease. AREAS COVERED: For the past three decades, research has been focused on systemic agents for the treatment of moderate-to-severe psoriasis, particularly with the introduction of biologic agents or 'small molecules'. In parallel, novel advances in topical antipsoriatic agents have been made, experiencing a 'new era', with the development of new formulations and the identification of new therapeutic targets. These agents, having a different spectrum of action from traditional agents, are actually being tested in pre-marketing clinical trials and they may potentially represent promising treatment options that could enlarge the therapeutic armamentarium for the treatment of psoriasis. EXPERT OPINION: Future antipsoriatic topical agents show new modality of action in blocking the pathogenic process leading to psoriatic plaque formation.

UVA-1 laser in the treatment of palmoplantar pustular psoriasis.

OBJECTIVE: The purpose of this study was to assess the efficacy of monochromatic UVA laser in the treatment of palmoplantar pustular psoriasis (PPP). BACKGROUND DATA: UVA-1 laser (355 nm) has been reported to be safe and effective in the treatment of psoriasis, but the range of potential applications has not been fully explored. METHODS: Thirty-three patients were enrolled in an open prospective study. Patients were treated from two to four times weekly at a fixed dose of 80-140 J/cm(2). Follow-up was 3 months. Clinical remission was observed in all patients who completed the study, with limited side effects (mild post-treatment erythema). CONCLUSIONS: We report for the first time that UVA-1 laser produces a therapeutic response in PPP.

Long-term ustekinumab treatment for refractory type I pityriasis rubra pilaris.

BACKGROUND: Pityriasis rubra pilaris is a rare, chronic erythematous squamous disorder of unknown etiology. The disease is characterized initially by small follicular papules that coalesce into yellowish pink scaly plaques, palmoplantar keratoderma, diffuse furfuraceous scale of the scalp, and frequent progression to exfoliative erythroderma. Generally it is difficult to discern pityriasis rubra pilaris from other skin conditions but key-clinical features help in the diagnosis such as "islands" of spared skin within generalized erythroderma, follicular keratotic plugs, and an orange hue of the involved skin. Treatment options include topical vitamin D analogues, keratolytics, systemic acitretin, methotrexate, cyclosporine, azathioprine, fumaric acid esters, phototherapy, and anti-TNFα agents. Cases, of pityriasis rubra pilaris, successfully treated with a short-course ustekinumab therapy, have been reported. MAIN OBSERVATIONS: We report a 31-year-old man with pityriasis rubra pilaris, refractory to conventional treatments, successfully treated with ustekinumab monotherapy for over 64 weeks. After failing conventional systemic agents (cyclosporine, aciretin and methotrexate), ustekinumab 45 mg has been prescribed, with the same dosing regimen as in psoriasis. The patient improved dramatically within 4 weeks of the first injection, with markedly less erythema and pruritus. Long-term control of the disease of the disease was achieved (64 weeks of treatment). CONCLUSION: We report this case in order to show the striking and rapid efficacy of ustekinumab in reducing the signs and symptoms of the disease. Complete remission was achieved after the third injection, but also a long-term control of the disease. The therapy was well-tolerated in our patient and no adverse events occurred.

Vitiligo treatment with monochromatic excimer light and tacrolimus: results of an open randomized controlled study.

BACKGROUND DATA: Narrow band ultraviolet B (UVB) is an effective and safe option for the treatment of vitiligo. However, a complete and long-lasting repigmention of vitiligo patches is difficult to achieve. Combined treatments with novel sources of phototherapy and topical agents represent possible new strategies. OBJECTIVE: The purpose of this study was to compare the efficacy of combined tacrolimus and 308-nm excimer light (MEL) vs 308-nm MEL monotherapy in treating vitiligo in a controlled study. METHODS: Fifty-three patients affected by vitiligo were enrolled in this open prospective study. Patients were divided into three groups: Group I included 20 patients treated with MEL 308 nm twice weekly and oral vitamin E; Group II included 20 patients treated with MEL 308 nm twice weekly combined with 0.1% tacrolimus once a day and oral vitamin E; and Group III included 13 patients treated only with oral vitamin E. Efficacy was assessed at the end of 12 weeks based on the percentage of repigmentation. RESULTS: Fifty-two patients completed 12 weeks of treatment. Group I (MEL + vitamin E) showed a moderate repigmentation in 35% of patients, good repigmentation in 30%, excellent repigmentation in 25%, and poor repigmentation in 10%; Group II (MEL + tacrolimus 0.1%+ vitamin E) presented moderate repigmentation in 25% of patients, good repigmentation in 40%, excellent repigmentation in 30%, and poor repigmentation in 5%; Group III (vitamin E) showed moderate repigmentation in 16% and 84% did not show signs of repigmentation. CONCLUSIONS: Our results demonstrate that the combination treatment of 0.1% tacrolimus ointment plus 308-nm MEL and 308-nm MEL monotherapy are effective, safe, and well tolerated for the treatment of vitiligo compared to treatment with vitamin E. Furthermore, this study suggests that an association with topical immunomodulators could enhance the clinical response in vitiligo, especially in more resistant anatomical sites.

Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly T(H)2/"T22" immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In patients with psoriasis, NB-UVB has been found to suppress T(H)1/T(H)17 polarization, with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in patients with AD. OBJECTIVE: We sought to evaluate the effects of NB-UVB on immune and barrier abnormalities in patients with AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. METHODS: Twelve patients with moderate-to-severe chronic AD received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and nonlesional skin biopsy specimens were obtained before and after treatment and evaluated by using gene expression and immunohistochemistry studies. RESULTS: All patients had at least a 50% reduction in SCORAD index scores with NB-UVB phototherapy. The T(H)2, T22, and T(H)1 immune pathways were suppressed, and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes and T(H)2/T22- associated cytokines and chemokines and normalized expression of barrier proteins. CONCLUSIONS: Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved T(H)2 and T22 inflammation in patients with chronic AD with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argue against a fixed genetic phenotype.

An occlusive dressing containing betamethasone valerate 0.1% for the treatment of prurigo nodularis.

INTRODUCTION: Prurigo nodularis is a distressing condition characterized by the presence of multiple nodules associated with intense pruritus. OBJECTIVE: To assess the clinical efficacy and safety of betamethasone valerate 0.1% tape and a moisturizing itch-relief cream in prurigo nodularis. METHODS: Twelve patients were enrolled in this pilot comparison of betamethasone valerate 0.1% tape versus a moisturizing itch-relief cream containing feverfew. The study period was 4 weeks. Clinical evaluation was performed weekly. RESULTS: Eleven subjects completed the 4 weeks of therapy. The mean visual analogue scale (VAS) for pruritus at baseline was 8.75 for both sides of the body. The side treated with betamethasone valerate 0.1% tape showed a higher clinical response (VAS score at week 4: 3.9; p < 0.005) compared with the side treated with moisturizing itch-relief cream (VAS score at week 4: 5.6; p < 0.005). CONCLUSION: Both treatments were effective. However, the occlusive dressing enhanced the efficacy of the treatment, preventing scratching.