Real-Life Effectiveness and Safety of Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Single-Center 16-Week Study.

INTRODUCTION: The treatment of severe atopic dermatitis (AD) includes cyclosporine and recently approved biologics and small molecules. Among these, upadacitinib is a selective inhibitor of Janus kinase 1, approved for the treatment of severe AD in adolescents/adults. Upadacitinib has shown efficacy and safety in several phase 3 clinical trials, but data on real-life patients are still lacking. METHODS: We conducted a retrospective real-life observational study to evaluate the effectiveness and safety of upadacitinib up to week 16 in a cohort of both bio-naïve and bio-experienced patients. This study was carried out by analyzing the AD database records of an Italian referral hospital. Thirty-eight patients were included in this study, and 35 completed 16 weeks of treatment. RESULTS: At week 16, out of 35 patients, the percentages of Eczema Area and Severity Index (EASI) 50, EASI 75, EASI 90 and EASI 100 responses were 94.29, 91.43, 74.29, and 60%, respectively. A decrease of at least 4 points from baseline of itch-NRS was reported by 94.74 and 91.43% of patients at weeks 8 and 16. Regarding the safety of upadacitinib, 26.32% of patients experienced at least one adverse event (AE), and a total of 13 AEs were recorded, including blood test abnormalities and papulopustular acne. None of our patients interrupted the drug because of an AE. CONCLUSIONS: We observed higher rates of EASI75/EASI90/EASI100 responses at week 16, compared with data from clinical trials. The safety profile of upadacitinib was favorable, as no AEs leading to discontinuation were experienced by our patients up to week 16.

Effectiveness and Safety of Upadacitinib in the Treatment of Moderate-Severe Atopic Dermatitis: A Multicentric, Prospective, Real-World, Cohort Study.

BACKGROUND: The efficacy and safety of upadacitinib in atopic dermatitis (AD) have been defined in clinical trials, but no real-world data are currently available. We aimed to assess the safety and effectiveness of upadacitinib in a real-world AD patient cohort that mostly included patients who failed the available systemic therapies, including dupilumab. METHODS: Prospective cohort study collecting data on upadacitinib-treated AD adult patients completing at least 16 weeks of therapy. RESULTS: Forty-three patients showed rapid and marked response to upadacitinib with significant reduction of all disease severity scores since the first follow-up visit. At week 16, Eczema Area and Severity Index (EASI) 75, EASI 90, and EASI 100 response was observed in 97.5%, 82.1%, and 69.2% of patients, respectively. EASI 90 response reflected the achievement of a clear or almost clear condition (POEM 0-2), self-evaluated by 79.5% of patients. Patients' quality of life improved as suggested by the achievement of DLQI 0/1 by 38.5% of patients at week 4, and by 76.9% at week 16. CONCLUSION: Elevated effectiveness and favorable safety of upadacitinib were confirmed in patients unresponsive to dupilumab, who were not included in upadacitinib trials.

Italian adaptation of EuroGuiDerm guideline on the systemic treatment of chronic plaque psoriasis.

SIDeMaST (Società Italiana di Dermatologia Medica, Chirurgica, Estetica e delle Malattie Sessualmente Trasmesse) contributed to the development of the present guideline on the systemic treatment of chronic plaque psoriasis. With the permission of EuroGuiDerm, SIDeMaST adapted the guideline to the Italian healthcare context to supply a reliable and affordable tool to Italian physicians who take care of patients affected by moderate to severe plaque psoriasis. The content of the guideline includes general information on the scope and purpose, health questions covered, target users and strength/limitations of the guideline, suggestions for disease severity grading and treatment goals. It presents the general treatment recommendations as well as detailed management and monitoring recommendations for the individual drugs including acitretin, cyclosporine, fumarates, methotrexate, adalimumab, apremilast, brodalumab, certolizumab pegol, etanercept, guselkumab, infliximab, ixekizumab, risankizumab, secukinumab, tildrakizumab and ustekinumab. Moreover, the guideline provides guidance for specific clinical situations such as patient with concomitant psoriatic arthritis, inflammatory bowel disease, a history of malignancies, a history of depression, diabetes, viral hepatitis, disease affecting the heart or the kidneys as well as concomitant neurological disease. Advice on how to screen for tuberculosis and recommendations on how to manage patients with a positive tuberculosis test result are given. It further covers treatment for pregnant women or those with childbearing potential. Information on vaccination, immunogenicity and systemic treatment during the COVID-19 pandemic is also provided.

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results.

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

Impact of delay in follow-up due to COVID-19 pandemic on skin cancer progression: a real-life experience from an Italian hub hospital.

BACKGROUND: The COVID-19 pandemic required the setting of a national lockdown in Italy from March 9, 2020, until May 18, 2020; therefore, most of the non-COVID-19 activities were postponed. As a consequence, many follow-up visits in patients with previously excised skin cancers were delayed. The aim of this retrospective real-life case-control study is demonstrating that delay in follow-up led to an increased incidence of advanced melanoma and keratinocyte cancers on the total of surgically excised skin cancers. METHODS: The incidence of excised advanced melanoma and keratinocyte cancers in our dermato-surgery division in the period May 18 to November 18, 2020, was compared to the same time span of 2019. All data were collected from the electronic database of our department. Odds ratio with 95% confidence interval was used to assess the risk of excised advanced skin cancers in 2020 compared to 2019. RESULTS: From May to November 2019, we performed 265 surgical excisions, while during the pandemic in 2020, we completed 280 surgeries. The number of advanced skin cancers excised between May 18 and November 18, 2020, was significantly higher compared with the same period in 2019 (54 vs. 22, OR: 2.64; 95% CI: 1.56-4.47; P = 0.0003). Significant differences were also observed regarding the number of surgically removed advanced BCCs (OR 2.15; 95% CI 1.14-4.07; P = 0.0187) and advanced SCCs (OR 4.60; 95% CI 1.31-16.18; P = 0.0175). CONCLUSION: These results confirm that delay in follow-up and, consequently, postponed surgical excisions are related to an increased incidence of advanced skin tumors, resulting in poorer prognosis lifelong. Follow-up visits should be carried on even during COVID-19 pandemic, avoiding significant delays as much as possible.

Incidence rates of hospitalization and death from COVID-19 in patients with psoriasis receiving biological treatment: A Northern Italy experience.

INTRODUCTION: Whether biologic therapies enhance the risk of coronavirus 2019 (COVID-19) or affect the disease outcome in patients with chronic plaque psoriasis remains to be ascertained. OBJECTIVE: We sought to investigate the incidence of hospitalization and death for COVID-19 in a large sample of patients with plaque psoriasis receiving biologic therapies compared with the general population. METHODS: This is a retrospective multicenter cohort study including patients with chronic plaque psoriasis (n = 6501) being treated with biologic therapy and regularly followed up at the divisions of dermatology of several main hospitals in the Northern Italian cities of Verona, Padua, Vicenza, Modena, Bologna, Piacenza, Turin, and Milan. Incidence rates of hospitalization and death per 10,000 person-months with exact mid-p 95% CIs and standardized incidence ratios were estimated in the patients with psoriasis and compared with those in the general population in the same geographic areas. RESULTS: The incidence rate of hospitalization for COVID-19 was 11.7 (95% CI, 7.2-18.1) per 10,000 person-months in patients with psoriasis and 14.4 (95% CI, 14.3-14.5) in the general population; the incidence rate of death from COVID-19 was 1.3 (95% CI, 0.2-4.3) and 4.7 (95% CI, 4.6-4.7) in patients with psoriasis and the general population, respectively. The standardized incidence ratio of hospitalization and death in patients with psoriasis compared with those in the general population was 0.94 (95% CI, 0.57-1.45; P = .82) and 0.42 (95% CI, 0.07-1.38; P = .19), respectively. CONCLUSIONS: Our data did not show any adverse impact of biologics on COVID-19 outcome in patients with psoriasis. We would not advise biologic discontinuation in patients on treatment since more than 6 months and not infected with severe acute respiratory syndrome coronavirus 2 to prevent hospitalization and death from COVID-19.

Autoinflammatory and autoimmune conditions at the crossroad of COVID-19.

Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known. In the remaining 20% of cases, the disease may become severe and/or critical. In most patients of this latter group, there is a phase characterized by the hyperresponsiveness of the immune system. A third phase corresponds to a state of hypercoagulability. Finally, in the fourth stage organ injury and failure occur. Appearance of autoinflammatory/autoimmune phenomena in patients with COVID-19 calls attention for the development of new strategies for the management of life-threatening conditions in critically ill patients. Antiphospholipid syndrome, autoimmune cytopenia, Guillain-Barré syndrome and Kawasaki disease have each been reported in patients with COVID-19. Here we present a scoping review of the relevant immunological findings in COVID-19 as well as the current reports about autoinflammatory/autoimmune conditions associated with the disease. These observations have crucial therapeutic implications since immunomodulatory drugs are at present the most likely best candidates for COVID-19 therapy. Clinicians should be aware of these conditions in patients with COVID-19, and these observations should be considered in the current development of vaccines.