Pfizer (Austria)

Introduction: Abrocitinib, an oral, once-daily, JAK1-selective inhibitor, is approved in patients aged ≥12 years at the recommended doses of 100 mg and 200 mg for the treatment of moderate-to-severe atopic dermatitis (AD). JADE REAL (NCT04564755) was a global, open-label expanded access protocol initiated in 2020 (completed September 2024) to provide access to abrocitinib for patients with moderate-to-severe AD. This analysis evaluated dosing patterns and incidence of treatment-emergent adverse events (TEAEs) leading to a change in dose of abrocitinib inpatients with moderate-to-severe AD in an expanded access protocol simulating real-world use of abrocitinib. Procedure/Study: Eligible patients aged ≥12 years with moderate-to-severe AD initiated once-daily abrocitinib 100 mg or 200 mg (plus topical medication as needed). The dose could be changed throughout the treatment period. Initial dosing and the proportion of patients with continuous dosing, ≥1 dose change and >1 dose change were assessed. Safety was assessed via TEAE monitoring. Results: Of 312 patients, 120 (38.5%) and 192 (61.5%) patients initiated abrocitinib 100 mg and 200 mg, respectively (mean [SD] treatment duration: 379.1 days [203.3]). More patients of ages ≥12–18 and ≥65 years, Black/African American race, and with moderate AD initiated abrocitinib 100 mg, while more patients of ages ≥18–<65 years, Asian race, and with severe AD initiated abrocitinib 200 mg. Of patients who initiated abrocitinib 100 mg and 200 mg, 78 (65.0%) and 119 (62.0%) received continuous dosing, and 42 (35.0%) and 73 (38.0%) patients had ≥1 dose change, including 12 (28.6%) and 33 (45.2%) patients with >1 dose change, respectively. TEAEs led to dose reduction in 27 patients (8.7%), notably nausea (n=4 [1.3%]), thrombocytopenia (n=4 [1.3%]), acne (n=3 [1.0%]), fatigue (n=3 [1.0%]), and folliculitis (n=3 [1.0%]). TEAEs led to a dose escalation in 12 patients (3.8%); AD was the only TEAE that occurred in ≥1% of patients (n=10 [3.2%]) which led to a dose escalation. Conclusion: Most patients received consistent abrocitinib dosing throughout the study. TEAEs were not the primary reason leading to dosage reduction. These results may support clinical decision making around initial dose selection and dosage changes. JADE REAL demonstrated the potential benefits of flexible dosing and may simulate the real-world use of oral Janus kinase inhibitors. Funding/Disclosures: This study was funded by Pfizer.

Tick-borne encephalitis (TBE) is an infection by the tick-borne encephalitis virus (TBEV) with symptoms of central nervous system inflammation. TBE is endemic in Latvia and other parts of Europe. TBE vaccination is recommended for children in Latvia. TBE vaccine effectiveness (VE) was estimated in Latvia, a country with high TBE incidence, providing the first VE estimates against a range of TBEV infection outcomes in children 1-15 years-of-age. Rīga Stradinš University conducted nationwide surveillance for suspected TBE cases. Serum and cerebrospinal fluid were ELISA tested for TBEV-specific IgG and IgM antibodies. A fully vaccinated child was an individual who had received the 3-dose primary series and appropriately timed boosters. The proportion of laboratory-confirmed TBE cases fully vaccinated (PCV) was determined from interviews and medical records. The proportion of the general population fully vaccinated (PPV) was determined from national surveys conducted in 2019 and 2020. TBE VE in children 1-15 years-of-age was estimated using the screening method: VE = 1 - [PCV/(1 - PCV)/PPV/(1 - PPV)]. From 2018 to 2020, surveillance identified 36 TBE cases in children 1-15 years-of-age; all were hospitalized, 5 (13.9%) for >12 days. Of the TBE cases, 94.4% (34/36) were unvaccinated compared with 43.8% of children in the general population. VE against TBE hospitalization in children 1-15 years-of-age was 94.9% (95% confidence interval 63.1-99.3). In 2018-2020, vaccination in children 1-15 years-of-age averted 39 hospitalized TBE cases. Pediatric TBE vaccines were highly effective in preventing TBE in children. Increasing TBE vaccine uptake in children is essential to maximize the public health impact of TBE vaccination.

Abstract Differences exist in the manifestation and disease course of atopic dermatitis (AD) between adult and adolescent patients. Long-term efficacy of abrocitinib (an oral, once-daily Janus kinase 1-selective inhibitor) was examined in the phase III extension study JADE EXTEND (NCT03422822). This interim post hoc analysis assessed abrocitinib treatment efficacy up to 96 weeks in adolescents and adults with moderate-to-severe AD who enrolled in JADE EXTEND. Eligible adolescents (aged 12 to < 18 years) and adults (≥ 18 years) from the phase III trials JADE MONO-1 (NCT03349060), MONO-2 (NCT03575871), COMPARE (NCT03720470), TEEN (NCT03796676) and DARE (NCT04345367) were enrolled in JADE EXTEND. Patients randomized to abrocitinib (200 mg or 100 mg) in the parent studies received blinded abrocitinib at the same dose in JADE EXTEND; those receiving placebo or dupilumab were randomized to either abrocitinib dose in JADE EXTEND. Patients from JADE DARE received abrocitinib 200 mg in JADE EXTEND. Analyses assessed the proportions of patients achieving an Investigator’s Global Assessment score of clear or almost clear (IGA 0/1); ≥ 75%, ≥ 90% and ≥ 100% improvement from baseline in Eczema Area and Severity Index (EASI-75, EASI-90 and EASI-100, respectively); ≥ 4-point improvement from baseline in Peak Pruritus Numerical Rating Scale score (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi); PP-NRS score of no or very little itch (PP-NRS 0/1); and ≥ 4-point improvement from baseline in the Patient Oriented Eczema Measure (POEM ≥ 4). The JADE EXTEND data cutoff date was 25 September 2021. This analysis included 357 adolescents and 1309 adults (excluding patients previously randomized to dupilumab). Age at parent study screening visit determined age categorization. Baseline disease severity was higher in adolescents than adults [IGA 4 (severe); 42.3% vs. 36.7%]. At week 96, responder proportions were comparable for adolescents and adults for EASI-75 (abrocitinib 200 mg: 84.4% vs. 85.7%; abrocitinib 100 mg: 81.3% vs. 76.1%), PP-NRS4 (200 mg: 69.4% vs. 69.3%; 100 mg: 60.3% vs. 59.8%) and POEM ≥ 4 (200 mg: 84.4% vs. 88.6%; 100 mg: 79.2% vs. 80.8%), and largely comparable for the stringent endpoints of EASI-90 (200 mg: 62.3% vs. 61.1%; 100 mg: 50.7% vs. 48.1%), EASI-100 (200 mg: 32.5% vs. 21.8%; 100 mg: 18.7% vs. 18.7%), IGA 0/1 (200 mg: 53.2% vs. 55.9%; 100 mg: 49.3% vs. 45.1%) and PP-NRS 0/1 (200 mg: 42.9% vs. 39.5%; 100 mg: 33.3% vs. 32.3%). Long-term efficacy of abrocitinib treatment up to 96 weeks was comparable for adolescents and adults with moderate-to-severe AD, including substantial proportions achieving stringent endpoints of EASI-90, EASI-100, IGA 0/1 or PP-NRS 0/1. Funding sources: Pfizer Inc.

Abstract Once-daily oral abrocitinib, a Janus kinase 1-selective inhibitor, was effective and well tolerated as a monotherapy in adult and adolescent patients with moderate-to-severe atopic dermatitis (AD), as well as in combination with medicated topical therapy in adolescents with moderate-to-severe AD. This study aims to investigate efficacy and safety of abrocitinib in adolescents with moderate-to-severe AD from the JADE clinical trial program. Patients aged 12–17 years with moderate-to-severe AD and an inadequate response to ≥4 consecutive weeks of topical medication or treatment with systemic therapy for AD, both within the past 6 months, were randomly assigned [2:2:1 JADE MONO-1/MONO-2 (NCT03349060/NCT03575871); 1:1:1 JADE TEEN (NCT03796676)] to receive once-daily oral abrocitinib (200 or 100 mg) or placebo as monotherapy (JADE MONO-1 and JADE MONO-2) or in combination with medicated topical therapy (JADE TEEN) for 12 weeks. Coprimary endpoints were proportion of patients achieving Investigator’s Global Assessment (IGA) response [clear (0) or almost clear (1) with ≥2-grade improvement from baseline] and proportion of patients who achieved ≥75% improvement in Eczema Area and Severity Index score (EASI-75) at Week 12. A key secondary endpoint was the proportion of patients achieving ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS4; used with permission from Regeneron Pharmaceuticals and Sanofi) at Week 12. Drug safety was also assessed. Overall, 285 and 124 adolescents in JADE TEEN and JADE MONO-1/MONO-2, respectively, were treated. In JADE TEEN, more abrocitinib-treated (200 mg, 100 mg) than placebo-treated patients achieved IGA (46.2%, 41.6% vs. 24.5%; P < 0.05 for both doses), EASI-75 (72.0%, 68.5% vs. 41.5%; P < 0.05 for both doses) and PP-NRS4 (55.4%, 52.6% vs. 29.8%; P < 0.01 for 200 mg vs. placebo) responses at Week 12. Adverse events (AEs) were reported for 62.8%, 56.8% and 52.1% of patients in 200 mg, 100 mg and placebo groups, respectively; 1 (1.1%), 0 and 2 patients (2.1%) had serious AEs. JADE MONO-1/MONO-2 safety results were similar, but efficacy results were lower, as expected for monotherapies. Results from JADE clinical trials suggest that abrocitinib was effective in adolescents with moderate-to-severe AD, with an acceptable safety profile.

ZusammenfassungRekombinantes humanes Wachstumshormon muss aufgrund seiner kurzen Halbwertszeit täglich injiziert werden. Dieses Behandlungsregime kann für Patient*innen und ihre Familien eine ganz erhebliche Belastung darstellen. Langwirksame Wachstumshormone (LAGH) sind eine neuartige Behandlungsoption, die durch eine 1‑mal wöchentliche Verabreichung eine reduzierte Injektionsfrequenz ermöglicht. Um erste Erkenntnisse über die Erwartungen an diese neuen LAGH-Formulierungen zu gewinnen, wurden zwei Umfragen bei Ärzt*innen sowie Eltern von Kindern, die täglich mit Wachstumshormon behandelt werden, in Österreich durchgeführt. Zwanzig Pädiater*innen/pädiatrische Endokrinolog*innen und 41 Eltern wurden befragt. Beide Umfragen zeigten, dass die LAGH-Formulierungen als positive Therapiealternative gesehen werden und dadurch eine Verbesserung der Lebensqualität erwartet wird.

Background:Lyme borreliosis (LB) is the most common tick-borne disease in Europe, but the burden of disease is incompletely described.Methods:We conducted a systematic review across PubMed, EMBASE, and CABI Direct (Global Health) databases, from January 1, 2005, to November 20, 2020, of epidemiological studies reporting incidence of LB in Europe (PROSPERO, CRD42021236906).Results:The systematic review yielded 61 unique articles describing LB incidence (national or subnational) in 25 European countries. Substantial heterogeneity in study designs, populations sampled, and case definitions restricted data comparability. The European Union Concerted Action on Lyme Borreliosis (EUCALB)–published standardized LB case definitions were used by only 13 (21%) of the 61 articles. There were 33 studies that provided national-level LB incidence estimates for 20 countries. Subnational LB incidence was available from an additional four countries (Italy, Lithuania, Norway, and Spain). The highest LB incidences (>100 cases per 100,000 population per year [PPY]) were reported in Belgium, Finland, the Netherlands, and Switzerland. Incidences were 20–40/100,000 PPY in the Czech Republic, Germany, Poland, and Scotland and <20/100,000 PPY in Belarus, Croatia, Denmark, France, Ireland, Portugal, Russia, Slovakia, Sweden, and the United Kingdom (England, Northern Ireland, and Wales); markedly higher incidences were observed at the subnational level (up to 464/100,000 PPY in specific local areas).Conclusions:Although countries in Northern (Finland) and Western (Belgium, the Netherlands, and Switzerland) Europe reported the highest LB incidences, high incidences also were reported in some Eastern European countries. There was substantial subnational variation in incidence, including high incidences in some areas of countries with low overall incidence. This review, complemented by the incidence surveillance article, provides a comprehensive view into LB disease burden across Europe that may guide future preventive and therapeutic strategies—including new strategies on the horizon.

Background:Public surveillance of Lyme borreliosis (LB) occurs in 9 out of 16 federal states of Germany and remains a critical facet of disease epidemiology and trends. We describe the incidence, time trends, seasonality, and geographic distribution of LB in Germany using publicly reported surveillance data.Methods:We obtained LB cases and incidence (2016−2020) from the online platform SurvStat@RKI 2.0, maintained by the Robert Koch Institute (RKI). Data included clinically diagnosed and laboratory-confirmed LB reported by nine out of 16 federal states of Germany where LB notification is mandatory.Results:During 2016−2020, the nine federal states reported 63,940 LB cases, of which 60,570 (94.7%) were clinically diagnosed, and 3370 (5.3%) also had laboratory confirmation, with an average of 12,789 cases annually. Incidence rates were mostly stable over time. The average annual LB incidence was 37.2/100,000 person-years and varied by spatial level, ranging from 22.9 to 64.6/100,000 person-years among nine states; from 16.8 to 85.6/100,000 person-years among 19 regions; and from 2.9 to 172.8/100,000 person-years among 158 counties. Incidence was lowest among persons 20–24 years old (16.1/100,000 person-years) and highest among those 65–69 years old (60.9/100,000 person-years). Most cases were reported between June and September, with a peak in July of every year.Conclusion:The risk of LB varied substantially at the smallest geographic unit and by age group. Our results underscore the importance of presenting LB data at the most spatially granular unit and by age to allow implementation of efficient preventive interventions and reduction strategies.

<b>Background:</b> Community-acquired pneumonia (CAP) is associated with major morbidity and mortality. Limited data are available on the burden of adult CAP in Greece. <b>Aims and objectives:</b> Our study aimed to estimate the incidence rates of adult hospitalized CAP in Greece during the period Nov2017-Oct2020. <b>Methods:</b> EGNATIA is a prospective study of adults ≥19yo hospitalized with clinical and radiographically-confirmed CAP in the Ioannina and Kavala regions of Greece. All hospitals of both cities that had departments routinely treating CAP patients were included in the study. Screening logs documented eligible but not enrolled patients. To identify eligible patients possibly missed by the screening procedures, we conducted a retrospective review of chest radiographs performed in all hospitals during Dec2019-Jan2020. <b>Results:</b> The overall hospitalized CAP incidence rate, before adjustment for patients missed by screening, was estimated at 1.65/1,000 population/year – 0.75 in 19-64yo and 4.1 in ≥65yo. After adjustment, it was estimated at 2.49/1,000 population/year - 0.88 in 19-64yo and 6.87 in ≥65yo (Table 1). <b>Conclusions:</b> Incidence rates of hospitalized CAP varied by region and year. Retrospective assessment revealed a considerable percentage of patients missed by study screening process, especially in the ≥65-year-old cohort, possibly due to comorbidities that took priority for treatment over CAP.

<b>Background:</b> SARS-CoV-2 has emerged as a novel pathogen of community-acquired pneumonia (CAP). <b>Aims and objectives:</b> We aimed to compare characteristics, clinical outcomes and pneumococcal identification in patients with COVID-19 vs non-COVID-19 CAP. <b>Methods:</b> EGNATIA is an ongoing, prospective study of adults ≥19yo hospitalized with clinical and radiographically-confirmed CAP in Greece. The primary objective is to estimate the proportion of CAP due to pneumococcal serotypes included in 13-valent pneumococcal conjugate vaccine (PCV13). Pneumococcus was identified using serotype-specific urinary antigen detection assays (UAD 1/2), BinaxNow® and conventional cultures. Testing for SARS-CoV-2 was performed as per national guidelines. <b>Results:</b> We compared 202 patients with COVID-19 pneumonia during Apr2020-Mar2021 vs 1033 patients with non-COVID-19 CAP during Nov2017-Oct2020. Patients with COVID-19 were younger (median age 68.8 vs 75.8 years) and had fewer comorbidities (67.8% with ≥1 underlying condition vs 79.2%) than non-COVID-19 patients. Patients with COVID-19 less frequently reported past pneumonia episodes (0.5% vs 7.7%) but were more frequently nursing home residents (13.9% vs 6%). Patients with COVID-19 had less severe pneumonia presentation (CURB 65 3-5 6.4% vs 30.5%; PSI IV-V 41.1% vs 55.2%) but required mechanical ventilation more frequently (7.4% vs 1.9%) and had a longer hospital stay (mean 17.4 vs 9.6 days). In-hospital mortality was similar between the 2 groups (7.9% in COVID-19 vs 8.9% in non-COVID-19). Pneumococcus was identified less frequently in patients with COVID-19 vs non-COVID-19 CAP (4% vs 11.1%). <b>Conclusions:</b> Significant differences were identified in patients with COVID-19 vs non-COVID-19 CAP.