Publications by authors named "Antonio Costanzo"

173 Publications

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

Drugs R D 2022 Aug 3. Epub 2022 Aug 3.

UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Largo Agostino Gemelli 8, 00168, Rome, Italy.

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.
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http://dx.doi.org/10.1007/s40268-022-00396-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9362214PMC
August 2022

Burden of Moderate to Severe Atopic Dermatitis in Adults from France, Italy, and the UK: Patient-Reported Outcomes and Treatment Patterns.

Dermatol Ther (Heidelb) 2022 Aug 1;12(8):1947-1965. Epub 2022 Aug 1.

Dermatology, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.

Introduction: Moderate to severe atopic dermatitis (AD) is associated with a significant disease burden, impacting sleep, quality of life, and treatment needs. The aim of this study was to characterize disease burden and treatment patterns for adults with moderate to severe AD in three European countries: France, Italy, and the UK.

Methods: This retrospective analysis of adult patients with moderate to severe AD in Europe used medical records and physician/patient survey data collected in August 2019 to April 2020. Demographic and baseline disease characteristics, information on current comorbidities, disease flares, and current and previous treatments were collected by the physician. Patient-perceived burden was assessed using patient-reported outcome (PRO) questionnaires, which were completed on a voluntary basis and included the following instruments: Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), EuroQol five-dimensional (EQ-5D), and Work Productivity and Activity Impairment (WPAI). Disease severity was subjectively assessed by physicians and was based on their own definition of the terms mild, moderate, and severe. Data were analyzed descriptively.

Results: The physician-reported sample included 912 patients with moderate to severe disease from France (n = 314), Italy (n = 309), and the UK (n = 289); approximately 30% of patients provided PRO data. Across these countries, 22-41% of patients reported current flares; mean POEM and DLQI scores were 10.6-13.1 and 9.5-11.1, respectively, indicating a high disease burden. However, systemic therapy use was low (e.g., conventional systemics were used by 18-24% of patients). Physician-assessed disease severity did not fully align with EASI scores, indicating that factors in addition to skin signs are impacting AD severity.

Conclusion: Patients with moderate to severe AD report significant disease burden, highlighting unmet treatment needs, particularly with respect to the underuse of systemic treatments despite AD being a systemic disease and the associated disease burden.
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http://dx.doi.org/10.1007/s13555-022-00777-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357584PMC
August 2022

Patient Characteristics and Treatment Patterns in European Pediatric Patients with Psoriasis: A Real-World, Cross-Sectional Study.

Dermatol Ther (Heidelb) 2022 Aug 7;12(8):1793-1808. Epub 2022 Jul 7.

Service de Dermatologie, Hôpital Victor Dupouy, 69, Rue du Lieutenant-Colonel Prud'hon, 95107, Argenteuil, France.

Introduction: This study evaluated patient characteristics and treatment patterns according to weight in pediatric patients with psoriasis in a real-world setting.

Methods: Primary care and specialist physicians treating pediatric patients with psoriasis aged 6-17 years in five European countries were surveyed in the 2019-2020 Adelphi Real World Pediatric Psoriasis Disease Specific Programme. At least two patients with current or previous biologic use were included per physician. Patient characteristics and treatment patterns were analyzed overall and for patients weighing 25-50 kg or more than 50 kg.

Results: Data from 772 patients weighing 25-50 kg and 1147 weighing more than 50 kg were analyzed. Median age at diagnosis was significantly less in lighter than heavier patients (10.0 vs. 14.0 years; p < 0.001), as was median disease duration (2.2 vs. 3.0 years; p < 0.001). Topical treatments were prescribed in 59.0% of patients overall (70.3% of lighter and 51.4% of heavier patients; p < 0.001), and were used to treat mild rather than moderate-to-severe psoriasis. Conventional systemic use was low (10.8% of patients overall) and predominantly for moderate-to-severe psoriasis. In this biologic-enriched sample, most biologics (78.2%) were prescribed in older (> 13 years) patients. Biologic use increased with line of therapy (6.6% of first-line, 18.0% of second-line, 33.7% of third-line, 44.7% of fourth-line treatments).

Conclusion: Biologics are predominantly prescribed in older (> 13 years) and heavier (> 50 kg) patients, with little first- or second-line use. The low use of biologics in European pediatric patients with psoriasis may represent an unmet treatment need, as topical or conventional systemic agents remain the main treatment option for moderate or severe psoriasis in these patients through the treatment pathway.
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http://dx.doi.org/10.1007/s13555-022-00761-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357581PMC
August 2022

Project R. Evolution for improving clinical research in Italy: challenges and strategies.

Curr Med Res Opin 2022 Jul 11:1-9. Epub 2022 Jul 11.

Comitato Etico Lazio 1, Rome, Italy.

Objective: The R.Evolution project aimed to reach a consensus on the main challenges of conducting clinical research in Italy and possible strategies and approaches to address them and optimize clinical research management.

Methods: A scientific board of experts initially discussed potentially critical areas in clinical research conduct and further explored them through an online national survey. The survey results were further examined by a group of 35 panelists representing different clinical research stakeholders. A Nominal Group Technique and a Delphi approach (two rounds) were used to generate a consensus on critical factors, tools and strategies in clinical research.

Results: Four main critical areas were identified: study feasibility, authorization procedures, operational aspects and patient management. The main issues are scarce awareness of the value of clinical research, lack of trained workforce and excessive complexity of protocols and administrative procedures. The Delphi panel identified six intervention areas: culture and patient involvement; procedures; staff, contracts, training and incentives; organization and infrastructure; administrative procedures; and ethics committee.

Conclusion: According to the R.Evolution project, possible strategies to improve clinical research management in Italy include a deeper understanding of the value of clinical research, the creation of long-term plans for hiring, training, organizing and motivating clinical trial staff, the simplification and harmonization of administrative procedures, as well as protocol design, and the development of stronger networks of centers and stakeholders.
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http://dx.doi.org/10.1080/03007995.2022.2091332DOI Listing
July 2022

Comparative effectiveness of biologics in clinical practice: week 12 primary outcomes from an international observational psoriasis study of health outcomes (PSoHO).

J Eur Acad Dermatol Venereol 2022 Jun 29. Epub 2022 Jun 29.

Paul Sabatier University and Larrey Hospital, Toulouse, France.

Background: Clinical trials study treatment outcomes under stringent conditions, capturing incompletely the heterogeneity of patient populations and treatment complexities encountered in real-world practice.

Objectives: To compare the effectiveness of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis.

Methods: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year observational cohort study in adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. Primary study endpoint is the proportion of patients achieving 90% improvement in Psoriasis Area and Severity Index (PASI 90) and/or static Physician Global Assessment (sPGA) 0/1 at Week 12 (W12) in the anti-IL-17A cohort (ixekizumab [IXE], secukinumab) vs. all other approved biologics. Secondary outcomes include the proportion of patients who achieve PASI 75/90/100, absolute PASI scores ≤5, ≤2 and ≤1, Dermatology Life Quality Index (DLQI) score of 0/1 at W12 between the two cohorts and among the individual biologics. Comparative effectiveness analyses were conducted using Frequentist Model Averaging (FMA), a novel causal inference machine learning approach. Missing data for binary outcomes were imputed as non-response.

Results: Patient profiles in the anti-IL-17A cohort and other biologics cohort were similar, with more frequent comorbid psoriatic arthritis and less frequent exposure to conventional treatments in the patients receiving anti-IL-17A biologics. At W12, 71.4% of patients who received an anti-IL-17A biologic achieved PASI 90 and/or sPGA 0/1 compared to 58.6% of patients who received other biologics (odds ratios [OR], 1.9; 95% confidence intervals [CI], [1.6, 2.4]). Similar findings were observed for secondary outcomes.

Conclusions: These results reflect the high efficacy and early onset of skin clearance of IL-17A inhibitors observed in randomized clinical trials and confirm the effectiveness of anti-IL-17A biologics in the real-world setting.
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http://dx.doi.org/10.1111/jdv.18376DOI Listing
June 2022

Urban Seismic Network Based on MEMS Sensors: The Experience of the Seismic Observatory in Camerino (Marche, Italy).

Sensors (Basel) 2022 Jun 8;22(12). Epub 2022 Jun 8.

School of Architecture and Design, University of Camerino, 63100 Ascoli Piceno, Italy.

Urban seismic networks are considered very useful tools for the management of seismic emergencies. In this work, a study of the first urban seismic network in central Italy is presented. The urban seismic network, built using MEMS sensors, was implemented in the urban district of Camerino, one of the cities in central Italy with the greatest seismic vulnerability. The technological choices adopted in developing this system as well as the implemented algorithms are shown in the context of their application to the first seismic event recorded by this innovative monitoring infrastructure. This monitoring network is innovative because it implements a distributed computing and statistical earthquake detection algorithm. As such, it is not based on the traces received by the stations from the central server; rather, each station carries out the necessary checks on the signal in real time, sending brief reports to the server in case of anomalies. This approach attempts to shorten the time between event detection and alert, effectively removing the dead times in the systems currently used in the Italian national network. The only limit for an instant alarm is the latency in the tcp/ip packages used to send the short reports to the server. The presented work shows the infrastructure created; however, there is not enough data to draw conclusions on this new early warning approach in the field, as it is currently in the data collection phase.
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http://dx.doi.org/10.3390/s22124335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228205PMC
June 2022

An apparent primitive mass of the mesentery: A case report.

Medicine (Baltimore) 2022 Jun 17;101(24):e29464. Epub 2022 Jun 17.

General Surgery Department, IRCCS MultiMedica, Italy.

Introduction: Neuroendocrine tumours (NETs) are rare tumors. 55% of NETs originate in the gastrointestinal tract and the liver is the most common site of distant metastases. Serum chromogranin A is the most common biomarker for assessing the extent of disease and monitoring treatment; carcinoid syndrome occurs in 19% of NETs and is characterized by chronic diarrhea or flushing. Primary mesenteric NETs are rare and have been described only in case reports in literature; our case is an apparent primary mesenteric NETs with a surgical program to remove the mesenteric mass and subrenal interaortocaval and retrocaval lymphadenectomies.

Patient Concerns: A 73-year old man came to us because he had been experiencing abdominal pain for a year and he had recently developed diabetes mellitus. He was an active smoker with arterial hypertension.

Diagnosis: After a computed tomography scan and 68 Gallium-positron emission tomography, a diagnosis of what appeared to be a primary mesenteric NET with retrocaval and interaortocaval lymph nodes was made. Laparoscopic biopsy showed NET G2 positive for serotonin, chromogranin A, synaptophysin.

Interventions: The intraoperative finding of a primitive ileum-NET changed the surgical program. We removed the mesenteric mass with the lymph nodes of the superior mesenteric vessel and the middle distal ileum along with the cecum.

Outcomes: The postoperative course was normal, and the patient was discharged on the seventh postoperative day without signs of short bowel syndrome. Follow-up at 6 months revealed no evidence of short bowel syndrome or disease progression.

Conclusion: 68 Gallium-positron emission tomography does not show NETs smaller than 0.5 mm. Accurate palpation of the intestine is essential during surgery for NETs for two reasons: to find the primitive, and because of the risk of multiple intestinal primitives.
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http://dx.doi.org/10.1097/MD.0000000000029464DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276447PMC
June 2022

The CANOVA Study Real-World Evidence of Biologic Treatments in Moderate-Severe Psoriasis in Italy: A Gender Perspective.

Womens Health Rep (New Rochelle) 2022 2;3(1):450-457. Epub 2022 May 2.

Novartis Farma S.p.A, Italy.

Background: In psoriasis, several studies have indicated sex differences in clinical characteristics, type of treatment, and outcomes. A higher impact of psoriasis on quality of life (QoL) and a lower treatment satisfaction have been reported in women by different authors.

Objectives: This article reports the results of a gender analysis of CANOVA study, aimed at assessing 16/24/52-week effectiveness of biologics in patients with moderate-severe plaque psoriasis.

Materials And Methods: CANOVA was a real-world, multicenter, noninterventional, retro-prospective study conducted in 17 Italian hospital dermatology clinics.

Results: Of the 669 eligible patients, 63.8% were men. Demographic and baseline characteristics and duration of disease were rather homogeneous between sexes. Slightly more women had been treated with biologics (50.4% vs. 46.5%) and had received ≥2 biologic treatment lines (17.2% vs. 12.4%) before study treatment. The most frequently used biologics were secukinumab, ustekinumab, adalimumab, and ixekizumab in both sexes. At 6 months, Psoriasis Area Severity Index (PASI) 75/90/100 responders were 90.8%/72.3%/45.3% of men and 89.2%/76.6%/48.2% of women. Sustained PASI responders were 79.5% of men and 75.9% of women. Treatment satisfaction was significantly lower in women at enrolment for all subscales, and was still lower at 6 months, no longer significantly. Gender distribution in Dermatology Life Quality Index total score classes showed a significantly greater effect of psoriasis on QoL in women, both at enrolment and at the 6-month follow-up.

Conclusions: In conclusion, this gender analysis confirms in both genders the efficacy of biologics in psoriasis. However, women reported a greater impact of the disease on QoL and lower treatment satisfaction.
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http://dx.doi.org/10.1089/whr.2021.0124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148641PMC
May 2022

Real life long-term efficacy and safety of ixekizumab in moderate-to-severe psoriasis: A 192 weeks multicentric retrospective study-IL PSO (Italian landscape psoriasis).

Dermatol Ther 2022 Aug 8;35(8):e15608. Epub 2022 Jun 8.

Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.

Psoriasis is one of the commonest inflammatory skin diseases determining a very high impact on patients' quality of life and daily activities and relationships. Several biologic therapies have been approved through the years for the treatment of moderate-to-severe plaque psoriasis, and efficacy and safety profile have been analyzed in clinical trials. Ixekizumab is an immunoglobulin G subclass 4 monoclonal antibody that selectively targets and binds IL-17A with high specificity and affinity. Inhibiting IL-17A activity, ixekizumab reduces and turns down levels of inflammation, resulting in the clinical improvement of the disease. Long-term efficacy and safety profile of ixekizumab have been investigated and reported in the UNCOVER trials, but in literature there are only few studies based on real life experience. We present the efficacy and safety profile of ixekizumab in a cohort of 779 patients affected by moderate-to-severe plaque psoriasis and treated with ixekizumab in 11 Italian dermatology hospitals, with a follow-up of care until 192 weeks.
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http://dx.doi.org/10.1111/dth.15608DOI Listing
August 2022

What Can IBD Specialists Learn from IL-23 Trials in Dermatology?

J Crohns Colitis 2022 May;16(Supplement_2):ii20-ii29

Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele (MI), Italy.

Background And Aims: The advent of biologic drugs revolutionised the treatment of many chronic inflammatory diseases in rheumatology, dermatology, and gastroenterology. The introduction of different targeted agents closely followed the increase in knowledge of pathogenic mechanisms. The identification of IL-23 as a master regulator of 'pathogenic' inflammation and the consequent efficacy of IL-23 blocking agents were first proofed in psoriasis and then in other inflammatory diseases such as psoriatic arthritis and Crohn's disease.

Methods: We reviewed all available results from anti-Il-23 clinical trials for psoriasis, focusing on data of IBDologists' interest. Regarding guselkumab, we analysed data from phase III clinical trials VOYAGE1, VOYAGE2, and NAVIGATE. For risankizumab, we reported efficacy and safety results from UltIMMa-1, UltIMMa-2, and IMMvent clinical trials, and tildrakizumab was evaluated by analysing data from reSURFACE1 and reSURFACE2 studies.

Results: Data from all the clinical trials that we reported showed both the efficacy of all three anti-IL-23 drugs in psoriasis and the safety of this class; in particular, no gastrointestinal side effects were observed in those studies. IL-23 blockers have shown promising short- and long-term results in psoriasis, with a major safety profile and no negative interactions with gastrointestinal system.

Conclusions: Anti-IL-23 indication for psoriatic arthritis is very recent and for IBD is still to come. Therefore, dermatologists are accumulating long-term experience with these drugs, both in clinical trials and in real-world evidence, which can help gastroenterologists in the management of IBD patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjac023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097670PMC
May 2022

Safety of Biologic Therapies in Patients with Moderate-to-Severe Plaque Psoriasis and Concomitant Viral Hepatitis: A Monocentric Retrospective Study.

Dermatol Ther (Heidelb) 2022 May 22;12(5):1263-1270. Epub 2022 Apr 22.

Dermatology Unit, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy.

Introduction: There are no strong data regarding the treatment with biologics (especially for the most recent anti-IL-17 and anti-IL-23 drugs) of patients with psoriasis and concomitant viral hepatitis. We assessed the safety of biologic drugs in patients with psoriasis who are seropositive for hepatitis B or C and did not receive antiviral prophylaxis.

Methods: We conducted a retrospective single-center study. The efficacy of biologic treatments was evaluated by assessing the Psoriasis Area and Severity Index (PASI) score during all visits, for a minimum follow-up of 52 weeks. All patients were evaluated by a hepatologist before starting the treatment. They were monitored for reactivation of viral hepatitis.

Results: Twenty patients had positive markers of hepatitis B virus (HBV) or hepatitis C virus (HCV). Seventeen patients had positive markers of HBV infection, and four patients had antibodies for HCV (one patient had serologic evidence of both infections). Anti-IL-23 biologics were the most used in our population, with risankizumab being the most prescribed drug. No patient had evidence of viral reactivation during our study. Study limitations include its retrospective nature and our inclusion of patients with different serological status receiving different biologic drugs.

Conclusion: Biologic therapies (including anti-IL-23 drugs) appear to be safe in patients seropositive for HCV or HBV core antibody who did not receive antiviral prophylaxis.
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http://dx.doi.org/10.1007/s13555-022-00726-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110615PMC
May 2022

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

Ital J Dermatol Venerol 2022 Feb;157(Suppl. 1 to No. 1):1-78

Section of Dermatology, Department of Clinical-Surgical, Diagnostic, and Pediatric Sciences, Foundation IRCCS Polyclinic San Matteo, University of Pavia, Pavia, Italy.

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.
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http://dx.doi.org/10.23736/S2784-8671.21.07132-2DOI Listing
February 2022

RIPK4 regulates cell-cell adhesion in epidermal development and homeostasis.

Hum Mol Genet 2022 Feb 26. Epub 2022 Feb 26.

Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.

Epidermal development and maintenance are finely regulated events requiring a strict balance between proliferation and differentiation. Alterations in these processes give rise to human disorders such as cancer or syndromes with skin and annexes defects, known as ectodermal dysplasias (EDs). Here, we studied the functional effects of two novel receptor-interacting protein kinase 4 (RIPK4) missense mutations identified in siblings with an autosomal recessive ED with cutaneous syndactyly, palmoplantar hyperkeratosis and orofacial synechiae. Clinical overlap with distinct EDs caused by mutations in transcription factors (i.e. p63 and interferon regulatory factor 6, IRF6) or nectin adhesion molecules was noticed. Impaired activity of the RIPK4 kinase resulted both in altered epithelial differentiation and defective cell adhesion. We showed that mutant RIPK4 resulted in loss of PVRL4/nectin-4 expression in patient epidermis and primary keratinocytes, and demonstrated that PVRL4 is transcriptionally regulated by IRF6, a RIPK4 phosphorylation target. In addition, defective RIPK4 altered desmosome morphology through modulation of plakophilin-1 and desmoplakin. In conclusion, this work implicates RIPK4 kinase function in the p63-IRF6 regulatory loop that controls the proliferation/differentiation switch and cell adhesion, with implications in ectodermal development and cancer.
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http://dx.doi.org/10.1093/hmg/ddac046DOI Listing
February 2022

Early predictors of psoriatic arthritis: a Delphi-based consensus from Italian dermatology centers.

Ital J Dermatol Venerol 2022 Jun 10;157(3):231-234. Epub 2022 Jan 10.

Unit of Dermatology, IRCCS Humanitas Clinic, Rozzano, Milan, Italy.

Background: Psoriatic arthritis (PsA) is an inflammatory condition which can affect up to 41% of psoriatic patients [1]. In 40-60% of patients, PsA can determine cartilage destruction and joint deformities, hereby heavily impacting physical function and quality of life, even increasing the risk of death compared to the general population [1]. PsA manifestations usually develop after psoriasis onset; therefore, dermatologists play a crucial role in the detection of early signs of arthritis. In our study, we aimed to identify simply detectable clinical and ecographic signs of early PsA and to assess their reliability.

Methods: We assessed the opinion of a group of expert dermatologists, who were asked to express their opinion on the level of association between the selected anamnestic, clinical or instrumental signs and the onset of psoriatic arthritis by giving a score to each item.

Results: Psoriatic onycopathy, signs of dactylitis and ultrasonographic alterations of selected joints were, respectively, the dermatologic, rheumatologic and imaging signs which had the strongest significance in the opinion of the experts.

Conclusions: These signs should be carefully looked for during dermatological examinations in order to detect early PsA.
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http://dx.doi.org/10.23736/S2784-8671.21.07203-0DOI Listing
June 2022

Physician‒Scientists in Italian Dermatology: Hurdles and Perspectives.

JID Innov 2022 Jan 25;2(1):100077. Epub 2021 Nov 25.

Dermatology Unit, Department of Biomedical Sciences, Humanitas University, Rozzano-Milan, Italy.

Physicians, including dermatologists, with expertise in clinical and basic research, play a pivotal role in the advancement of medical science. Although the number of residents in dermatology has been increasing and our specialty is among the most requested in Italy, the disaffection of young dermatologists for research is a chronic and apparently irreversible trend. This commentary analyzes the reasons and suggests some ideas to counteract this alarming tendency.
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http://dx.doi.org/10.1016/j.xjidi.2021.100077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717572PMC
January 2022

The biological basis of disease recurrence in psoriasis: a historical perspective and current models.

Br J Dermatol 2022 05;186(5):773-781

Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.

A key challenge in psoriasis therapy is the tendency for lesions to recur in previously affected anatomical locations after treatment discontinuation following lesion resolution. Available evidence supports the concept of a localized immunological 'memory' that persists in resolved skin after complete disappearance of visible inflammation, as well as the role of a specific subpopulation of T cells characterized by the dermotropic CCR4 phenotype and forming a local memory. Increasing knowledge of the interleukin (IL)-23/T helper 17 (Th17) cell pathway in psoriasis immunopathology is pointing away from the historical classification of psoriasis as primarily a Th1-type disease. Research undertaken from the 1990s to the mid-2000s provided evidence for the existence of a large population of CD8 and CD4 tissue-resident memory T cells in resolved skin, which can initiate and perpetuate immune responses of psoriasis in the absence of T-cell recruitment from the blood. Dendritic cells (DCs) are antigen-presenting cells that contribute to psoriasis pathology via the secretion of IL-23, the upstream regulator of Th17 cells, while plasmacytoid DCs are involved via IL-36 signalling and type I interferon activation. Overall, the evidence discussed in this review indicates that IL-23-driven/IL-17-producing T cells play a critical role in psoriasis pathology and recurrence, making these cytokines logical therapeutic targets. The review also explains the clinical efficacy of IL-17 and IL-23 receptor blockers in the treatment of psoriasis.
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http://dx.doi.org/10.1111/bjd.20963DOI Listing
May 2022

Long-term management of moderate-to-severe adult atopic dermatitis: a consensus by the Italian Society of Dermatology and Venereology (SIDeMaST), the Association of Italian Territorial and Hospital Allergists and Immunologists (AAIITO), the Italian Association of Hospital Dermatologists (ADOI), the Italian Society of Allergological, Environmental and Occupational Dermatology (SIDAPA), and the Italian Society of Allergy, Asthma and Clinical Immunology (SIAAIC).

Ital J Dermatol Venerol 2022 Feb 21;157(1):1-12. Epub 2021 Dec 21.

Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy.

Atopic dermatitis (AD) is a common chronic-relapsing inflammatory skin disease, burdened by various comorbidities. AD most commonly occurs in children but may persist or present in adulthood becoming a lifelong condition. Therefore, AD requires an effective long-term treatment improving disease signs and symptoms but also of patients' quality of life (QoL). However continuous long-term use of most traditional AD immunosuppressive treatments is not recommended for safety reasons or insufficient efficacy data. Despite the available guidelines, there is still need for knowledge of AD long-term treatment, taking into account new disease measures and recent treatment options. Five Italian scientific societies implemented a joint consensus procedure to define the most appropriate clinical practice for the long-term management of adult moderate-severe AD. Through a modified Delphi procedure, consensus was reached by overall 51 Italian dermatologists and allergists (The Italian AD Study Group) experienced in the management of adult AD on 14 statements covering three AD areas of interest, namely diagnosis, definition of disease severity and clinimetrics, and a treat-to-target approach. This paper reports and discusses the agreed statements, which define disease and patient impact measures, therapeutic approach, and a treatment decision algorithm to support clinicians in the long-term management of adult patients with moderate-to-severe AD in their daily clinical practice.
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http://dx.doi.org/10.23736/S2784-8671.21.07129-2DOI Listing
February 2022

DNA Methylation Signature in Monozygotic Twins Discordant for Psoriatic Disease.

Front Cell Dev Biol 2021 24;9:778677. Epub 2021 Nov 24.

Division of Rheumatology and Clinical Immunology, Humanitas Research Hospital IRCCS, Rozzano, Italy.

Psoriatic disease is a multifactorial inflammatory condition spanning from skin and nail psoriasis (Pso) to spine and joint involvement characterizing psoriatic arthritis (PsA). Monozygotic twins provide a model to investigate genetic, early life environmental exposure and stochastic influences to complex diseases, mainly mediated by epigenetics. We performed a genome-wide DNA methylation study on whole blood of monozygotic twins from 7 pairs discordant for Pso/PsA using the Infinium Methylation EPIC array (Illumina). MeDiP-qPCR was used to confirm specific signals. Data were replicated in an independent cohort of seven patients with Pso/PsA and 3 healthy controls. Transcriptomic profiling was performed by RNAsequence on the same 7 monozygotic twin pairs. We identified 2,564 differentially methylated positions between psoriatic disease and controls, corresponding to 1,703 genes, 59% within gene bodies. There were 19 regions with at least two DMPs within 1 kb of distance and significant within-pair Δ-values ( < 0.005), among them SNX25, BRG1 and SMAD3 genes, all involved in TGF-β signaling pathway, were identified. Co-expression analyses on transcriptome data identified IL-6/JAK/STAT3 and TNF-α pathways as important signaling axes involved in the disease, and they also suggested an altered glucose metabolism in patients' immune cells, characteristic of pro-inflammatory T lymphocytes. The study suggests the presence of an epigenetic signature in affected individuals, pointing to genes involved in immunological and inflammatory responses. This result is also supported by transcriptome data, that altogether suggest a higher activation state of the immune system, that could promote the disease status.
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http://dx.doi.org/10.3389/fcell.2021.778677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653905PMC
November 2021

A Technological System for Post-Earthquake Damage Scenarios Based on the Monitoring by Means of an Urban Seismic Network.

Sensors (Basel) 2021 Nov 26;21(23). Epub 2021 Nov 26.

National Earthquake Observatory, Istituto Nazionale di Geofisica e Vulcanologia, 00143 Rome, Italy.

A technological system capable of automatically producing damage scenarios at an urban scale, as soon as an earthquake occurs, can help the decision-makers in planning the first post-disaster response, i.e., to prioritize the field activities for checking damage, making a building safe, and supporting rescue and recovery. This system can be even more useful when it works on densely populated areas, as well as on historic urban centers. In the paper, we propose a processing chain on a GIS platform to generate post-earthquake damage scenarios, which are based: (1) on the near real-time processing of the ground motion, that is recorded in different sites by MEMS accelerometric sensor network in order to take into account the local effects, and (2) the current structural characteristics of the built heritage, that can be managed through an information system from the local public administration authority. In the framework of the EU-funded H2020-ARCH project, the components of the system have been developed for the historic area of Camerino (Italy). Currently, some experimental fragility curves in the scientific literature, which are based on the damage observations after Italian earthquakes, are implemented in the platform. These curves allow relating the acceleration peaks obtained by the recordings of the ground motion with the probability to reach a certain damage level, depending on the structural typology. An operational test of the system was performed with reference to an ML3.3 earthquake that occurred 13 km south of Camerino. Acceleration peaks between 1.3 and 4.5 cm/s were recorded by the network, and probabilities lower than 35% for negligible damage (and then about 10% for moderate damage) were calculated for the historical buildings given this low-energy earthquake.
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http://dx.doi.org/10.3390/s21237887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659508PMC
November 2021

Apremilast for the treatment of palmo-plantar non-pustular psoriasis: A real-life single-center retrospective study.

Dermatol Ther 2022 02 26;35(2):e15253. Epub 2021 Dec 26.

Dermatology Unit, Humanitas Clinical and Research Center - IRCCS, Milan, Italy.

Palmoplantar psoriasis (PP) is a type of psoriasis that involves the skin of the palms and soles and can present as hyperkeratotic, similar to the vulgaris psoriasis of the body. Apremilast, as an oral inhibitor of phosphodiesterase 4 (PDE4), is currently approved for the treatment of psoriatic arthritis and for moderate-to-severe psoriasis in adult patients who have not responded or have contraindications or do not tolerate other systemic treatments. We evaluated the efficacy and safety of apremilast in the treatment of non-pustular palmo-plantar psoriasis in a cohort of 12 patients. We found a clinical response of clear/almost clear palmoplantar psoriasis (PPPGA score 0/1) in 83.33% of our patients, at week 16. No significant safety issues were reported and none of our patients had to discontinue the drug.
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http://dx.doi.org/10.1111/dth.15253DOI Listing
February 2022

Assessing the Beneficial Impact of a Patient Support Program in Secukinumab-Treated Patients with Psoriasis in Italy.

Patient Prefer Adherence 2021 19;15:2551-2562. Epub 2021 Nov 19.

Dermatology Unit, Tor Vergata University Hospital, Rome, Italy.

Purpose: For patients with psoriasis, treatment adherence and persistence are fundamental if therapeutic goals are to be met. Patient Support Programs (PSPs) may be used as a support tool to assist patients and health care professionals optimize treatment and improve disease management.

Patients And Methods: In Italy, the PSP PSOLife CARE, which began on the 9th of February 2017 and is ongoing, aimed to support patients with psoriasis under therapy with secukinumab (Cosentyx). A team of medical professionals including Dermatologists, Psychologists, Nutritionists, and field Nurses provided outpatient treatment as well as remote support via phone calls. Patients had a standard duration in the Program of 6 months. This report analyzes the data of patients who benefited from the Program from February 2017 to August 2020, for a total observation of 42 months.

Results: We provide here a descriptive report on the benefits of participation in the PSOLife CARE Program for patients with psoriasis and medical professionals involved in their care. Throughout their time in the PSOLife CARE Program, patient satisfaction remained consistently high with sustained improvements observed in all aspects of quality of life (ie emotional, social, physical, and economic). Despite exiting from the Program, most patients continued to adhere to secukinumab. Medical professionals also reported positive outcomes on their interactions with patients, with more than half of those surveyed rating the overall quality of the Program as "Outstanding".

Conclusion: By supporting treatment adherence, the PSOLife CARE Program may have empowered patients to better manage their psoriasis, increasing their satisfaction with treatment and quality of life.
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http://dx.doi.org/10.2147/PPA.S326498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8610754PMC
November 2021

Anti-IL17 and anti-IL23 biologic drugs for scalp psoriasis: A single-center retrospective comparative study.

Dermatol Ther 2022 02 30;35(2):e15228. Epub 2021 Nov 30.

Department of Dermatology, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy.

Scalp is a frequent localization of psoriasis that has a massive impact on patient's quality of life. Managing this psoriasis' manifestation is often challenging, thus biologic drugs are widely used as a treatment option in refractory scalp psoriasis. The aim of our study is to retrospectively compare the efficacy of anti-interleukin (IL) 23 drugs (guselkumab, tildrakizumab, risankizumab) and anti-IL17 or anti-IL17RA biologics (secukinumab, ixekizumab, and brodalumab) in real-life patients affected by scalp psoriasis. One hundred twenty-seven patients with a clinical diagnosis of scalp psoriasis and a baseline scalp Physician Global Assessment ≥3 were enrolled; 65 patients were treated with anti-IL23 and anti-IL62 with anti-IL17 or anti-IL17RA. Statistical analysis trough χ test was performed in order to evaluate the percentage of response among the two groups of patients. Responders' percentage of patients under anti-IL23 was 41.5%, 75.4%, 88.1%, 87.5%, 93.7%, and 100% at Week 4, 16, 48, 96, and 144, respectively. In the group on anti-IL17 was 62.9%, 90.3%, 91.2%, 97.3%, 96.9%, and 95.2% at Week 4, 16, 48, 96, and 144, respectively. Both anti-IL17 and anti-IL23 appeared to be effective on scalp psoriasis; in particular patients treated with anti-IL17 drugs reached a faster significant reduction of the lesions; on the other hand, anti-IL23 monoclonal antibodies were slightly superior in maintaining the clinical improvement through the follow-up.
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http://dx.doi.org/10.1111/dth.15228DOI Listing
February 2022

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.

Dermatol Ther 2022 01 23;35(1):e15166. Epub 2021 Nov 23.

Dermatology, A.O.U. Città della Salute e della Scienza PO Molinette, Turin, Italy.

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.
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http://dx.doi.org/10.1111/dth.15166DOI Listing
January 2022

Connective tissue panniculitis and vitiligo in a patient with stage IV melanoma achieving complete response to dabrafenib and trametinib combination therapy.

Melanoma Res 2021 12;31(6):586-588

Department of Biomedical Sciences - Humanitas University, Pieve Emanuele (MI).

The combination of BRAF and MEK inhibitors, such as dabrafenib and trametinib, respectively, is an established treatment option for patients with advanced BRAFV600-mutated melanoma. With the wide adoption of these therapies, a range of cutaneous adverse effects has been reported. We describe the case of a 47-year-old woman with BRAFV600E-mutated stage IV melanoma treated with dabrafenib and trametinib for 30 months who presented to our attention for painful skin lesions that had been present on her limbs since the start of targeted therapy. We also observed vitiligo-like lesions on the extensor surface of both legs. Despite achieving a complete oncological response, the patient had to discontinue the treatment because of persisting fever, nausea and painful skin nodules that significantly impaired her quality of life. The recognition of cutaneous signs of efficacy of such drugs for advanced melanoma is of primary importance in order to identify patients with potential long-term clinical benefits.
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http://dx.doi.org/10.1097/CMR.0000000000000787DOI Listing
December 2021

Real-life Effectiveness and Safety of Risankizumab in Moderate-to-severe Plaque Psoriasis: A 40-week Multicentric Retrospective Study.

Acta Derm Venereol 2021 Nov 30;101(11):adv00605. Epub 2021 Nov 30.

Department of Biomedical Sciences, Humanitas University, Dermatology Unit, Humanitas Clinical and Research Center - IRCCS, Via Rita Levi Montalcini, 4, IT-20090 Pieve Emanuele MI, Italy.

Risankizumab is a humanized monoclonal antibody that binds the p19 subunit of interleukin-23. It is approved for treatment of moderate-severe chronic plaque psoriasis. This retrospective study included 66 consecutive adults with moderate-to-severe psoriasis vulgaris treated with risankizumab in monotherapy up to week 40 in a "real-life" setting. At week 40, 98.7%, 85.7% and 62.3% of patients achieved a Psoriasis Area and Severity Index (PASI) reduction ≥ 75% (PASI 75), PASI 90 and PASI 100, respectively. Patients who had not responded to 2 or more previous biologic treatments were significantly less likely to achieve PASI 75/90 at week 16 and PASI 90/100 at week 40 compared with those who had been previously treated with only 1 biologic, and compared with those treated with risankizumab as a first-line biologic. Increasing body mass index decreased the chances of reaching PASI 90 at week 40. No significant safety findings were recorded throughout the study, and none of the patients had to interrupt the treatment. These data suggest that the efficacy of risankizumab for plaque psoriasis in "real-life" clinical practice could differ from pivotal clinical trials data.
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http://dx.doi.org/10.2340/actadv.v101.283DOI Listing
November 2021

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

BMC Health Serv Res 2021 Sep 6;21(1):924. Epub 2021 Sep 6.

A.O.U. Città della Salute e della Scienza PO Molinette, Turin, Italy.

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.
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http://dx.doi.org/10.1186/s12913-021-06866-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422702PMC
September 2021

Unmet needs in atopic dermatitis management: an expert consensus.

J Dermatolog Treat 2022 Aug 27;33(5):2459-2465. Epub 2021 Aug 27.

Department of Medicine, Section of Dermatology, University of Verona, Verona, Italy.

Introduction: Atopic dermatitis (AD) has substantial negative impact on patients' quality of life. Although considerable advances have been made in understanding the pathogenesis and its treatment, there is still limited transfer of this knowledge into daily management. Aiming to identify unmet needs in clinical management of patients with AD, we used a Delphi consensus process.

Methods: A set of statements regarding diagnosis, management, prognosis, and treatment was identified by five experts (Steering Committee). Then, the Steering Committee and a second group of four clinicians were involved in a Delphi process. Lastly, agreement was assessed in a larger panel of Italian clinicians.

Results: Overall, 37 clinicians participated to the process. 17 statements reached strong agreement and 2 reached weak agreement.

Conclusions: In general, the statements reflected the need for accurate and effective diagnostic criteria to support clinical experience, especially in the atypical forms of AD. Moreover, prognostic criteria are needed to predict the duration of adult-onset AD. The identification of biomarkers was considered to be useful for clinical management of AD at all stages of disease. Lastly, greater emphasis should be placed on patient education and development of effective tools that can aid informing patients about their disease and its treatment.
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http://dx.doi.org/10.1080/09546634.2021.1967267DOI Listing
August 2022

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

J Allergy Clin Immunol 2022 03 14;149(3):977-987.e14. Epub 2021 Aug 14.

Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

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.
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http://dx.doi.org/10.1016/j.jaci.2021.07.036DOI Listing
March 2022

Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial.

JAMA Dermatol 2021 Sep;157(9):1047-1055

Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.

Importance: Atopic dermatitis (AD) is a chronic, recurrent, inflammatory skin disease with an unmet need for treatments that provide rapid and high levels of skin clearance and itch improvement.

Objective: To assess the safety and efficacy of upadacitinib vs dupilumab in adults with moderate-to-severe AD.

Design, Setting, And Participants: Heads Up was a 24-week, head-to-head, phase 3b, multicenter, randomized, double-blinded, double-dummy, active-controlled clinical trial comparing the safety and efficacy of upadacitinib with dupilumab among 692 adults with moderate-to-severe AD who were candidates for systemic therapy. The study was conducted from February 21, 2019, to December 9, 2020, at 129 centers located in 22 countries across Europe, North and South America, Oceania, and the Asia-Pacific region. Efficacy analyses were conducted in the intent-to-treat population.

Interventions: Patients were randomized 1:1 and treated with oral upadacitinib, 30 mg once daily, or subcutaneous dupilumab, 300 mg every other week.

Main Outcomes And Measures: The primary end point was achievement of 75% improvement in the Eczema Area and Severity Index (EASI75) at week 16. Secondary end points were percentage change from baseline in the Worst Pruritus Numerical Rating Scale (NRS) (weekly average), proportion of patients achieving EASI100 and EASI90 at week 16, percentage change from baseline in Worst Pruritus NRS at week 4, proportion of patients achieving EASI75 at week 2, percentage change from baseline in Worst Pruritus NRS (weekly average) at week 1, and Worst Pruritus NRS (weekly average) improvement of 4 points or more at week 16. End points at week 24 included EASI75, EASI90, EASI100, and improvement of 4 points or more in Worst Pruritus NRS from baseline (weekly average). Safety was assessed as treatment-emergent adverse events in all patients receiving 1 or more dose of either drug.

Results: Of 924 patients screened, 348 (183 men [52.6%]; mean [SD] age, 36.6 [14.6] years) were randomized to receive upadacitinib and 344 were randomized to receive dupilumab (194 men [56.4%]; mean [SD] age, 36.9 [14.1] years); demographic and disease characteristics were balanced among treatment groups. At week 16, 247 patients receiving upadacitinib (71.0%) and 210 patients receiving dupilumab (61.1%) achieved EASI75 (P = .006). All ranked secondary end points also demonstrated the superiority of upadacitinib vs dupilumab, including improvement in Worst Pruritus NRS as early as week 1 (mean [SE], 31.4% [1.7%] vs 8.8% [1.8%]; P < .001), achievement of EASI75 as early as week 2 (152 [43.7%] vs 60 [17.4%]; P < .001), and achievement of EASI100 at week 16 (97 [27.9%] vs 26 [7.6%]; P < .001). Rates of serious infection, eczema herpeticum, herpes zoster, and laboratory-related adverse events were higher for patients who received upadacitinib, whereas rates of conjunctivitis and injection-site reactions were higher for patients who received dupilumab.

Conclusions And Relevance: During 16 weeks of treatment, upadacitinib demonstrated superior efficacy vs dupilumab in patients with moderate-to-severe AD, with no new safety signals.

Trial Registration: ClinicalTrials.gov Identifier: NCT03738397.
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http://dx.doi.org/10.1001/jamadermatol.2021.3023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340015PMC
September 2021

Real-life efficacy of guselkumab in patients with early psoriatic arthritis.

Rheumatology (Oxford) 2022 03;61(3):1217-1221

Dipartimento di Medicina di Precisione, Rheumatology Unit.

Objectives: To assess the efficacy of the novel anti-IL-23 monoclonal antibody guselkumab in a real-life observational cohort of patients with early PsA.

Methods: We conducted an observational study on patients with early PsA followed by the joint dermatology-rheumatology clinics of two Italian centres starting therapy with guselkumab for severe skin involvement. Each patient was evaluated at baseline and every 24 weeks for one year, recording Disease Activity Index for PsA (DAPSA), PASI, VAS Pain, VAS Prutitus, Patient's Global Assessment (PtGA) and assessing DAPSA response.

Results: Twenty-four patients were recruited (16 women). The mean duration of skin disease was 12.5 years (CI 8; 17), but all patients had a shorter articular disease duration, 21.29 months (CI 15.9; 26.68). At baseline, all patients displayed a moderate cutaneous disease with a mean PASI of 15.2 (CI 11.7-18.6) and high disease activity, characterized by mean DAPSA of 26.84 (CI 22.49-31.19). An inflammatory low back pain was reported by five patients (20%) with a mean BASDAI 5.1 (CI 4,38-5,85) at baseline. The majority of guselkumab-treated patients (n = 18; 75%) reached DAPSA remission or DAPSA low disease activity after six months. Seventeen out of 24 patients completed 12 months of treatment, 11 of them (65%) in low disease activity, six (35%) in remission. All patients with axial disease reported improvement of inflammatory low back pain at week 24 with a mean BASDAI 2.98 (CI 2,18- 3,77). No significant side effects were reported.

Conclusions: Real-life data on a cohort of early PsA patients confirm the efficacy and safety of guselkumab on peripheral and axial manifestations.
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http://dx.doi.org/10.1093/rheumatology/keab509DOI Listing
March 2022
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