217 results on '"Markus Magerl"'
Search Results
2. Berotralstat for hereditary angioedema with C1 inhibitor deficiency: a practical guide for clinicians
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Adil Adatia and Markus Magerl
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hereditary angioedema ,C1 inhibitor ,kallikrein ,berotralstat ,immunodeficiency ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2024
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3. Advent of oral medications for the treatment of hereditary angioedema
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Anna Valerieva, Teresa Caballero, Markus Magerl, Joao P. Frade, Paul K. Audhya, and Timothy Craig
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berotralstat ,deucrictibant ,hereditary angioedema ,oral ,sebetralstat ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life‐threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on‐demand treatment in all patients and the prevention of attacks (short‐term prophylaxis [STP] and long‐term prophylaxis [LTP]) in appropriate patients. All approved on‐demand and most LTP medications require subcutaneous or intravenous administration. Injection‐related challenges include trypanophobia (fear of needles), difficulty with self‐administration, injection‐site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers. Aim To review oral therapies, approved or in development, for on‐demand treatment and/or prevention of HAE attacks. Materials and Methods To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024). Results Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on‐demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on‐demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE‐4666, and VE‐4062) are in early development for LTP. Conclusion Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE.
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- 2024
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4. The real life experience goes on: update after 4 years on the first cohort treated with lanadelumab at our center
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Thomas Buttgereit, Carolina Vera Ayala, Seda Aykanat, Karsten Weller, Annika Gutsche, Marcus Maurer, and Markus Magerl
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lanadelumab ,hereditary angioedema ,real-life ,control ,quality of life ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionLanadelumab is a first-line long-term prophylaxis (LTP) in hereditary angioedema (HAE). Real-life data on its long-term efficacy and safety are limited. It is unknown whether patients using lanadelumab need short-term prophylaxis (STP).ObjectivesTo provide 4-year follow-up data for our first 34 patients treating with lanadelumab.MethodsPatients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AE-QoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab.ResultsOf 34 patients who started lanadelumab treatment, 32 were still using it after 4 years, with a median injection interval of 33 (range 14-90) days. HAE patients (n=28) reported longer intervals, i.e. 35 (14-90) days, than patients with angioedema due to acquired C1 inhibitor deficiency (n=4, 23 (14-31) days). With their current injection intervals, used for a mean duration of 29 ± 17 months, patients reported a yearly attack rate of 0.3 ± 0.1. More than 70% of patients were attack-free since starting their current injection interval. All patients reported well-controlled disease, i.e. ≥10 points in the AECT; 21 patients had complete control (16 points). AE-QoL scores improved further compared to our initial report, most prominently in the fears/shame domain (-6 points). Treatment satisfaction was very high. No angioedema occurred after 146 of 147 potentially attack-inducing medical procedures without STP.ConclusionsOur results demonstrate the long-term efficacy and safety of lanadelumab in real-life and question the need for STP in patients who use effective LTP.
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- 2024
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5. The current situation of hereditary angioedema patients in Germany: results of an online survey
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Markus Magerl, Inmaculada Martinez-Saguer, Lucia Schauf, Sven Pohl, and Klaus Brendel
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hereditary angioedema ,burden of disease ,long-term prophylaxis ,quality of life ,disease control ,disease management ,Medicine (General) ,R5-920 - Abstract
IntroductionHereditary angioedema (HAE) is a rare hereditary disease with an estimated prevalence of approximately 1 in 50,000.MethodsAn online survey was performed between January and June 2021 on a total of 99 HAE patients (with 92 of them aged 15 years and older and 7 of them being parents of patients under the age of 15 years). They were asked about their current situation, with a focus on the disease.ResultsThe survey results show that HAE has a strong influence on the patients’ quality of life. In particular, the anxiety and uncertainty of not knowing when a swelling attack will occur is considered burdensome by the patients. In addition, there can be physical problems during an attack (depending on its severity) that severely burden and limit patients in their everyday lives. Only one-third of the patients surveyed stated that no or only very minor physical limitations occurred during their most recent swelling attack. Almost three-quarters of all patients receive regular treatment at an HAE center. The patients are mostly satisfied with the therapy and particularly with long-term prophylactics (LTPs). When an LTP was used, the frequency and severity of the swelling attacks, and their duration, were significantly lower and/or shorter than when no LTP was used.DiscussionDespite the high level of satisfaction with their current medication, 62% of patients expressed a strong/very strong interest in an oral LTP. In the group of patients already using an LTP, 74% reported a strong/very strong interest in an oral medication for long-term prophylaxis. The simplicity and minimal time involved in LTP use are considered beneficial to patients’ quality of life.
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- 2024
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6. A multicenter chart review of patient characteristics, treatment, and outcomes in hereditary angioedema: unmet need for more effective long-term prophylaxis
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Joan Mendivil, Maral DerSarkissian, Aleena Banerji, Lavanya Diwakar, Constance H. Katelaris, Paul K. Keith, Harold Kim, Gina Lacuesta, Markus Magerl, Charlotte Slade, William B. Smith, Zia Choudhry, Angela Simon, Sujata P. Sarda, and Paula J. Busse
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Hereditary angioedema ,C1 inhibitor deficiency ,Long-term prophylaxis ,On-demand treatment ,Androgens ,Retrospective chart review ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Hereditary angioedema (HAE) is a rare disease characterized by unpredictable, recurring subcutaneous or submucosal swelling. Without effective therapy, HAE can negatively impact patients’ quality of life. Management of HAE includes on-demand treatment of attacks and short- and long-term prophylaxis (LTP) to prevent attacks. Newer therapies may be more tolerable and effective in managing HAE; however, therapies such as androgens are still widely used in some countries owing to their relative ease of access and adequate disease control for some patients. This study evaluated the characteristics, treatment patterns, clinical outcomes, and healthcare resource utilization of a multinational cohort of patients with HAE, with a focus on understanding reasons for recommending or discontinuing available therapies. Methods A retrospective chart review was conducted at 12 centers in six countries and included data from patients with HAE type 1 or 2 who were ≥ 12 years of age at their first clinical visit. The relationship between LTP use and attack rates was evaluated using a multivariable Poisson regression model. Data were collected between March 2018 and July 2019. Results Data from 225 patients were collected (62.7% female, 86.2% White, 90.2% type 1); 64.4% of patients had their first HAE-related visit to the center prior to or during 2014. Treatment patterns varied between countries. Overall, 85.8% of patients were prescribed on-demand treatment and 53.8% were prescribed LTP, most commonly the androgen danazol (53.7% of patients who used LTP). Plasma-derived C1 inhibitor (Cinryze®) was used by 29.8% of patients for LTP. Patients who received LTP had a significantly lower rate of HAE attacks than patients who did not receive any LTP (incidence rate ratio (95% confidence interval) 0.90 (0.84–0.96)). Androgens were the most commonly discontinued therapy (51.3%), with low tolerability cited as the most frequent reason for discontinuation (50.0%). Conclusions Overall, findings from this study support the use of LTP in the prevention of HAE attacks; a lower rate of attacks was observed with LTP compared with no LTP. However, the type of LTP used varied between countries, with tolerability and accessibility to specific treatments playing important roles in management decision-making.
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- 2023
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7. Could it be hereditary angioedema?—Perspectives from different medical specialties
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Markus Magerl, Anna Sala‐Cunill, Christina Weber‐Chrysochoou, Susanne Trainotti, Ilaria Mormile, and Giuseppe Spadaro
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bradykinin ,C1‐esterase inhibitor ,differential diagnosis ,hereditary angioedema ,rare disease ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Hereditary angioedema (HAE) is a rare autosomal dominant disease, with patients often suffering with associated symptoms for many years before receiving a correct diagnosis. The symptoms greatly impact a patient's quality of life (QoL) and include excruciating abdominal pain and angioedema of the skin and submucosa. Angioedema of the larynx represents a significant mortality risk in undiagnosed patients, and a large proportion of patients with HAE receive incorrect diagnoses and undergo unnecessary surgery. HAE‐specific treatments can control and prevent acute life‐threatening episodes, in addition to improving QoL, emphasizing the value of early diagnosis for patients. Diagnostic delay may be due to a lack of HAE awareness by healthcare professionals and the similarity of HAE symptoms with those of more common conditions, complicating differential diagnosis. The multifaceted nature of the condition may result in visits to one of many different medical settings, for example: the Emergency Room, pediatrics, general practice, otolaryngology, gastroenterology, and dermatology. Therefore, it is crucial that physicians in multiple healthcare specialties are aware of the disease to ensure that patients with HAE receive a timely diagnosis. Using patient cases from various medical specialties, this review highlights the necessity for cross‐specialty awareness of HAE and outlines the essential information for the various healthcare professionals that may encounter a patient with HAE symptoms, in order to effectively treat and/or diagnose HAE.
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- 2023
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8. Sensitivity to change and minimal clinically important difference of the angioedema control test
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Lauré M. Fijen, Carolina Vera, Thomas Buttgereit, Hanna Bonnekoh, Marcus Maurer, Markus Magerl, and Karsten Weller
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angioedema ,disease control ,minimal clinically important difference (MCID)7 ,patient‐reported outcome measures (PROMs) ,sensitivity to change ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The Angioedema Control Test (AECT) is a patient‐reported outcome measure developed and validated for the assessment of disease control in patients with recurrent angioedema. Its sensitivity to change and minimal clinically important difference (MCID) have hitherto not been established. Methods Patients with recurrent angioedema due to chronic spontaneous urticaria, hereditary angioedema, or acquired C1‐inhibitor deficiency were repeatedly asked to complete the AECT along with the Angioedema Quality of Life Questionnaire (AE‐QoL), Dermatology Life Quality Index (DLQI), and anchors for disease control and whether treatment was sufficient during routine care visits. The sensitivity to the change of the AECT was determined by correlating changes in its scores over time with changes in the applied anchors. The MCID was determined using anchor‐based and distributional criterion‐based approaches. Results Eighty‐six cases were used for this analysis. Changes in AECT scores correlated well with AE‐QoL changes (but less with changes in the DLQI) as well as other applied anchors, demonstrating its sensitivity to change. The MCID was found to be three points for improvement of angioedema control. The available number of cases with meaningful deterioration in our dataset was too low to reach a definite conclusion on the MCID for deterioration of angioedema control. Conclusion The AECT is a valuable tool to assess changes in disease control in patients with recurrent angioedema over time. The lowest AECT score change that reflects a meaningful improvement of disease control to patients (MCID) is three points.
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- 2023
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9. Patient‐physician interactions in hereditary angioedema—Key learnings from the coronavirus disease 2019 pandemic
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Marcus Maurer, Thomas Buttgereit, Markus Magerl, Kathrin Schön, Zsusanna Balla, and Henriette Farkas
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COVID‐19 pandemic ,disease control ,hereditary angioedema ,relationship ,shared decision‐making ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background The coronavirus disease pandemic and its containing measures have caused concerns for patients with hereditary angioedema (HAE) and their treating physicians. Both faced challenges surrounding interaction, and communication had to adapt to facilitate appropriate management. Specifically, the pandemic resulted in reduced in‐person contact in clinics. Where possible, telemedicine appointments were offered and treatment outside the hospital setting was encouraged. Body The pandemic markedly affected patient‐physician communication, which is essential to maintain partnerships and optimize care. Although patients with HAE are often experts in their condition, guidance by their physicians is essential, especially with the recent shift toward patient‐centered management for rare diseases and shared decision‐making (SDM). SDM enables patients to take control of their disease and allows the risks and benefits of treatment to be discussed with their physicians. This review explores perspectives from patients and physicians in the HAE clinical setting, particularly regarding their experiences with communication throughout the pandemic. We discuss the importance of SDM in rare diseases such as HAE, factors that impact effective communication, and potential solutions. Conclusion Since patient‐centered care and SDM have particular relevance in rare diseases in general, we believe our findings could be transferrable and applicable in the management of other rare diseases.
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- 2023
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10. Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series
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Marcus Maurer, Markus Magerl, Emel Aygören-Pürsün, Konrad Bork, Henriette Farkas, Hilary Longhurst, Sorena Kiani‑Alikhan, Laurence Bouillet, Isabelle Boccon-Gibod, Mauro Cancian, Andrea Zanichelli, and David Launay
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Angioedema, hereditary ,Prophylaxis ,Attenuated androgens ,Danazol ,Oxandrolone ,Case series ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects. As better tolerated targeted therapies become available, attenuated androgen withdrawal is increasingly considered by physicians and their patients with HAE. Attenuated androgens withdrawal has not been systematically studied in HAE, although examination of other disorders indicates that attenuated androgen withdrawal may result in mood disturbances and flu-like symptoms. Standardized protocols for attenuated androgen discontinuation that continue to provide control of attacks while limiting potential attenuated androgen withdrawal symptoms are not established as the outcomes of different withdrawal strategies have not been compared. We aim to describe the challenges of attenuated androgen discontinuation in patients with HAE and how these may continue into the post-androgen period. Case presentation We present a retrospective case series of 10 patients with confirmed type I HAE who have discontinued prophylactic treatment with attenuated androgens. The most common reason for attenuated androgen discontinuation was side effects. Attenuated androgens were either immediately withdrawn, tapered and/or overlapped with another treatment. The major challenge of discontinuation was the management of an increased frequency and severity of HAE attacks in some patients. Conclusions Healthcare teams need to undertake careful planning and monitoring after attenuated androgens discontinuation, and modify treatment strategies if HAE control is destabilized with an increased number of attacks. Discontinuation of attenuated androgens is definitively an option in an evolving HAE treatment landscape, and outcomes can be favourable with additional patient support and education.
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- 2022
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11. Case report: Recurrent angioedema: Diagnosing the rare and the frequent
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Thomas Buttgereit, Lauré M. Fijen, Carolina Vera, Karl-Christian Bergmann, Marcus Maurer, and Markus Magerl
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angioedema ,recurrent ,mast cell ,omalizumab ,normal C1INH ,HAE ,Medicine (General) ,R5-920 - Abstract
Hereditary angiodema with normal C1 inhibitor and unknown mutation (HAE-nC1INH-UNK), an exceedingly rare subtype of HAE, appears to be often diagnosed in patients who do not have this condition, but have mast cell-mediated angioedema. Here, we report two patients diagnosed with HAE-nC1INH-UNK by their physicians, who referred them to our center for treatment continuation with costly kallikrein-kinin-system targeted therapies. We describe how we established the correct diagnosis of recurrent mast cell-mediated angioedema after thorough investigation of both patients and initiated effective treatment with omalizumab. Also, we present and discuss the consensus criteria for diagnosing the very rare condition HAE-nC1INH in light of recent research and based on our own clinical experience. In conclusion, HAE-nC1INH-UNK should only be considered after more common differential diagnoses, i.e., mast cell-mediated angioedema, have thoroughly been investigated and ruled out. This approach reduces both the patients’ disease burden and healthcare costs and contributes to meaningful research.
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- 2022
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12. HAE patient self-sampling for biomarker establishment
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Toni M. Förster, Markus Magerl, Marcus Maurer, Selen Zülbahar, Susanne Zielke, Neil Inhaber, Donatello Crocetta, Arndt Rolfs, and Volha Skrahina
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Hereditary angioedema ,Observational clinical study ,Biomarker ,Cleaved high molecular weight Kininogen ,Self-sampling ,Medicine - Abstract
Abstract Background Hereditary Angioedema (HAE) is a genetic disorder that leads to frequent angioedema attacks in various parts of the body. In most cases it is caused by pathogenic variants in the SERPING1 gene, coding for C1-Inhibitor (C1-INH). The pathogenic variants in the gene result in reduced C1-INH levels and/or activity, which causes aberrant bradykinin production and enhanced vascular permeability. The standard-of-care diagnostic test is performed biochemically via measuring C1-INH level and activity as well as the C4 level. This, however, does not allow for the diagnosis of HAE types with normal C1-INH. There is an urgent need to identify and characterize HAE biomarkers for facilitating diagnostics and personalizing the treatment. The Hereditary Angioedema Kininogen Assay (HAEKA) study aims to measure the dynamics of cleaved High Molecular Weight Kininogen (HKa) and other metabolite levels during the angioedema and non-angioedema state of the disease. The metabolites will be analyzed and verified by liquid chromatography ion mobility high resolution mass spectrometry (LC/IM-QToF MS) of dried blood spot (DBS) cards upon the study completion. The study design is truly innovative: 100 enrolled participants provide blood samples via DBS: (1) every 3 months within 2 years during regular study site visits and (2) by at-home self-sampling during HAE attacks via finger pricking. We are presenting a project design that permits clinical study activities during pandemic contact restrictions and opens the door for other clinical studies during COVID-19. Results As of October 2020, there are 41 patients from 5 sites in Germany enrolled. 90 blood samples were collected during the regular visits, and 19 of the participants also performed self-sampling during the HAE attacks from which a total of 286 attack blood samples were collected. Participating patients rate the study procedures as easy to implement in their daily lives. The concept of home self-sampling is effective, reproducible, and convenient especially in times of contact restrictions due to the COVID-19 pandemic. Conclusions It is the hope that the HAEKA study will complete in 2023, reveal biomarker(s) for monitoring HAE disease activity, and may help to avoid HAE attacks via applying medication prior to the symptom onset.
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- 2021
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13. Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE)
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Faidra Parsopoulou, Gedeon Loules, Maria Zamanakou, Dorottya Csuka, Agnes Szilagyi, Maria Kompoti, Grzegorz Porebski, Fotis Psarros, Markus Magerl, Anna Valerieva, Maria Staevska, Krystyna Obtulowicz, Marcus Maurer, Matthaios Speletas, Henriette Farkas, and Anastasios E. Germenis
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C1-inhibitor deficiency ,genetic biomarkers ,functional variants ,hereditary angioedema ,long-term prophylaxis ,next-generation sequencing ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Existing evidence indicates that modifier genes could change the phenotypic outcome of the causal SERPING1 variant and thus explain the expression variability of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). To further examine this hypothesis, we investigated the presence or absence of 18 functional variants of genes encoding proteins involved in the metabolism and function of bradykinin, the main mediator of C1-INH-HAE attacks, in relation to three distinct phenotypic traits of patients with C1-INH-HAE, i.e., the age at disease onset, the need for long-term prophylaxis (LTP), and the severity of the disease. Genetic analyses were performed by a validated next-generation sequencing platform. In total, 233 patients with C1-INH-HAE from 144 unrelated families from five European countries were enrolled in the study. Already described correlations between five common functional variants [F12-rs1801020, KLKB1-rs3733402, CPN1-rs61751507, and two in SERPING1 (rs4926 and rs28362944)] and C1-INH-HAE severity were confirmed. Furthermore, significant correlations were found between either the age at disease onset, the LTP, or the severity score of the disease and a series of other functional variants (F13B-rs6003, PLAU-rs2227564, SERPINA1-rs28929474, SERPINA1-rs17580, KLK1-rs5515, SERPINE1-rs6092, and F2-rs1799963). Interestingly, correlations uncovered in the entire cohort of patients were different from those discovered in the cohort of patients carrying missense causal SERPING1 variants. Our findings indicate that variants other than the SERPING1 causal variants act as independent modifiers of C1-INH-HAE severity and could be tested as possible prognostic biomarkers.
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- 2022
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14. Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study
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William R. Lumry, Bruce Zuraw, Marco Cicardi, Timothy Craig, John Anderson, Aleena Banerji, Jonathan A. Bernstein, Teresa Caballero, Henriette Farkas, Richard G. Gower, Paul K. Keith, Donald S. Levy, H. Henry Li, Markus Magerl, Michael Manning, Marc A. Riedl, John-Philip Lawo, Subhransu Prusty, Thomas Machnig, Hilary Longhurst, and on behalf of the COMPACT Investigators
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C1-inhibitor protein ,Hereditary angioedema ,Patient-reported outcomes ,Health-related quality of life ,Productivity ,Subcutaneous ,Medicine - Abstract
Abstract Background Long-term prophylaxis with subcutaneous C1-inhibitor (C1-INH[SC]; HAEGARDA, CSL Behring) in patients with hereditary angioedema (HAE) due to C1-INH deficiency (C1-INH-HAE) was evaluated in an open-label extension follow-up study to the international, double-blind, placebo-controlled COMPACT study. The current analysis evaluated patient-reported health-related quality of life (HRQoL) data from 126 patients in the open-label extension study randomized to treatment with C1-INH(SC) 40 IU/kg (n = 63) or 60 IU/kg (n = 63) twice weekly for 52 weeks. HRQoL was evaluated at the beginning of the open-label study and at various time points using the European Quality of Life-5 Dimensions Questionnaire (EQ-5D), the Hospital Anxiety and Depression Scale (HADS), the Work Productivity and Activity Impairment Questionnaire (WPAI), and the Treatment Satisfaction Questionnaire for Medication. The disease-specific Angioedema Quality of Life Questionnaire (AE-QoL) and HAE quality of life questionnaire (HAE-QoL) instruments were administered in a subset of patients. Statistical significance was determined by change-from-baseline 95% confidence intervals (CIs) excluding zero. No adjustment for multiplicity was done. Results Mean baseline EQ-5D scores (Health State Value, 0.90; Visual Analog Scale, 81.32) were slightly higher (better) than United States population norms (0.825, 80.0, respectively) and mean HADS anxiety (5.48) and depression (2.88) scores were within “normal” range (0–7). Yet, patients using C1-INH(SC) 60 IU/kg demonstrated significant improvement from baseline to end-of-study on the EQ-5D Health State Value (mean change [95% CI], 0.07 [0.01, 0.12] and Visual Analog Scale (7.45 [3.29, 11.62]). In the C1-INH(SC) 60 IU/kg group, there were significant improvements in the HADS anxiety scale (mean change [95% CI], − 1.23 [− 2.08, − 0.38]), HADS depression scale (− 0.95 [− 1.57, − 0.34]), and WPAI-assessed presenteeism (mean change [95% CI], − 23.33% [− 34.86, − 11.81]), work productivity loss (− 26.68% [− 39.92, − 13.44]), and activity impairment (− 16.14% [− 26.36, − 5.91]). Clinically important improvements were achieved in ≥ 25% of patients for all domains except WPAI-assessed absenteeism (which was very low at baseline). Mean AE-QoL total score by visit ranged from 13.39 to 17.89 (scale 0–100; lower scores = less impairment). Mean HAE-QoL global scores at each visit (115.7–122.3) were close to the maximum (best) possible score of 135. Conclusions Long-term C1-INH(SC) replacement therapy in patients with C1-INH-HAE leads to significant and sustained improvements in multiple measures of HRQoL. Trial registration A Study to Evaluate the Long-term Clinical Safety and Efficacy of Subcutaneously Administered C1-esterase Inhibitor in the Prevention of Hereditary Angioedema, NCT02316353. Registered December 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02316353 .
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- 2021
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15. A Germany-wide survey study on the patient journey of patients with hereditary angioedema
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Markus Magerl, Holger Gothe, Simon Krupka, Anja Lachmann, and Christoph Ohlmeier
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Hereditary angioedema ,Diagnostic delay ,Germany ,Rare disease ,Survey ,Medicine - Abstract
Abstract Background Hereditary angioedema (HAE) is a rare genetic disease and characterized by clinical features such as paroxysmal, recurrent angioedema of the skin, the gastrointestinal tract, and the upper airways. Swelling of the skin occurs primarily in the face, extremities and genitals. Gastrointestinal attacks are accompanied by painful abdominal cramps, vomiting and diarrhea. Due to the low prevalence and the fact that HAE patients often present with rather unspecific symptoms such as abdominal cramps, the final diagnosis is often made after a long delay. The aim of this German-wide survey was to characterize the period between occurrence of first symptoms and final diagnosis regarding self-perceived health, symptom burden and false diagnoses for patients with HAE. Results Overall, 81 patients with HAE were included and participated in the telephone-based survey. Of those, the majority reported their current health status as “good” (47.5%) or “very good” (13.8%), which was observed to be a clear improvement compared to the year before final diagnosis (“good” (16.3%), “very good” (11.3%)). Edema in the extremities (85.2%) and in the gastrointestinal tract (81.5%) were the most currently reported symptoms and occurred earlier than other reported symptoms (mean age at onset 18.1 and 17.8 years, respectively). Misdiagnoses were observed in 50.6% of participating HAE patients with appendicitis and allergy being the most frequently reported misdiagnoses (40.0 and 30.0% of those with misdiagnosis, respectively). Patients with misdiagnosis often received mistreatment (80.0%) with pharmaceuticals and surgical interventions as the most frequently carried out mistreatments (65.6 and 56.3% of those with mistreatment, respectively). The mean observed diagnostic delay was 18.1 years (median 15.0 years). The diagnostic delay was higher in older patients and index patients. Conclusions This study showed that self-perceived status of health for patients is much better once the final correct diagnosis has been made and specific treatment was available. Further challenge in the future will still be to increase awareness for HAE especially in settings which are normally approached by patients at occurrence of first symptoms to assure early referral to specialists and therefore increase the likelihood of receiving an early diagnosis.
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- 2020
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16. A novel deep intronic SERPING1 variant as a cause of hereditary angioedema due to C1-inhibitor deficiency
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Sofia Vatsiou, Maria Zamanakou, Gedeon Loules, Fotis Psarros, Faidra Parsopoulou, Dorottya Csuka, Anna Valerieva, Maria Staevska, Grzegorz Porebski, Krystyna Obtulowicz, Markus Magerl, Marcus Maurer, Matthaios Speletas, Henriette Farkas, and Anastasios E. Germenis
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C1-inhibitor deficiency ,Hereditary angioedema ,Intronic mutations ,Next-generation sequencing ,SERPING1 gene ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: In about 5% of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) no mutation in the SERPING1 gene is detected. Methods: C1-INH-HAE cases with no mutation in the coding region of SERPING1 after conventional genotyping were examined for defects in the intronic or untranslated regions of the gene. Using a next-generation sequencing (NGS) platform targeting the entire SERPING1, 14 unrelated C1-INH-HAE patients with no detectable mutations in the coding region of the gene were sequenced. Detected variants with a global minor allele frequency lower than the frequency of C1-INH-HAE (0.002%), were submitted to in silico analysis using ten different bioinformatics tools. Pedigree analysis and examination of their pathogenic effect on the RNA level were performed for filtered in variants. Results: In two unrelated patients, the novel mutation c.-22-155G > T was detected in intron 1 of the SERPING1 gene by the use NGS and confirmed by Sanger sequencing. All bioinformatics tools predicted that the variant causes a deleterious effect on the gene and pedigree analysis showed its co-segregation with the disease. Degradation of the mutated allele was demonstrated by the loss of heterozygosity on the cDNA level. According to the American College of Medical Genetics and Genomics 2015 guidelines the c.-22-155G > T was curated as pathogenic. Conclusions: For the first time, a deep intronic mutation that was detected by NGS in the SERPING1 gene, was proven pathogenic for C1-INH-HAE. Therefore, advanced DNA sequencing methods should be performed in cases of C1-INH-HAE where standard approaches fail to uncover the genetic alteration.
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- 2020
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17. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update
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Marcus Maurer, MD, Markus Magerl, MD, Stephen Betschel, MD, Werner Aberer, MD, Ignacio J. Ansotegui, MD, PhD, Emel Aygören-Pürsün, MD, Aleena Banerji, MD, Noémi-Anna Bara, MD, Isabelle Boccon-Gibod, MD, Konrad Bork, MD, Laurence Bouillet, Pr, MD, PhD, Henrik Balle Boysen, Nicholas Brodszki, MD, PhD, Paula J. Busse, MD, Anette Bygum, MD, DMSci, Teresa Caballero, MD, PhD, Mauro Cancian, MD, PhD, Anthony J. Castaldo, Danny M. Cohn, MD, PhD, Dorottya Csuka, MD, Henriette Farkas, MD, PhD, DSc, Mark Gompels, MBBS, BSc, MD, Richard Gower, MD, Anete S. Grumach, MD, PhD, Guillermo Guidos-Fogelbach, MD, PhD, Michihiro Hide, MD, PhD, Hye-Ryun Kang, MD, PhD, Allen P. Kaplan, MD, Constance H. Katelaris, MBBS, PhD, Sorena Kiani-Alikhan, PhD, Wei-Te Lei, MD, Richard F. Lockey, MD, Hilary Longhurst, PhD, William Lumry, MD, Andrew MacGinnitie, MD, PhD, Alejandro Malbran, MD, PhD, Inmaculada Martinez Saguer, MD, Juan José Matta Campos, MD, Alexander Nast, MD, Dinh Nguyen, MD, PhD, Sandra A. Nieto-Martinez, MD, Ruby Pawankar, MD, PhD, Jonathan Peter, MB ChB, MMed, FCP (SA), PhD, Grzegorz Porebski, MD, Nieves Prior, MD, PhD, Avner Reshef, MD, Marc Riedl, MD, Bruce Ritchie, MD, Farrukh Rafique Sheikh, MBBS, William B. Smith, MBBS, PhD, Peter J. Spaeth, PhD, Marcin Stobiecki, MD, Elias Toubi, MD, Lilian Agnes Varga, PhD, Karsten Weller, MD, Andrea Zanichelli, MD, Yuxiang Zhi, MD, Bruce Zuraw, MD, and Timothy Craig, MD
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Hereditary angioedema ,C1-inhibitor ,diagnosis ,GRADE therapy ,management ,disease control ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Hereditary Angioedema (HAE) is a rare and disabling disease for which early diagnosis and effective therapy are critical. This revision and update of the global WAO/EAACI guideline on the diagnosis and management of HAE provides up-to-date guidance for the management of HAE. For this update and revision of the guideline, an international panel of experts reviewed the existing evidence, developed 28 recommendations, and established consensus by an online DELPHI process. The goal of these recommendations and guideline is to help physicians and their patients in making rational decisions in the management of HAE with deficient C1-inhibitor (type 1) and HAE with dysfunctional C1-inhibitor (type 2), by providing guidance on common and important clinical issues, such as: 1) How should HAE be diagnosed? 2) When should HAE patients receive prophylactic on top of on-demand treatment and what treatments should be used? 3) What are the goals of treatment? 4) Should HAE management be different for special HAE patient groups such as children or pregnant/breast feeding women? 5) How should HAE patients monitor their disease activity, impact, and control? It is also the intention of this guideline to help establish global standards for the management of HAE and to encourage and facilitate the use of recommended diagnostics and therapies for all patients.
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- 2022
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18. Chronic urticaria patients are interested in apps to monitor their disease activity and control: A UCARE CURICT analysis
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Ivan Cherrez‐Ojeda, Emanuel Vanegas, Annia Cherrez, Miguel Felix, Karsten Weller, Markus Magerl, Rasmus Robin Maurer, Valeria L. Mata, Alicja Kasperska‐Zajac, Agnieszka Sikora, Daria Fomina, Elena Kovalkova, Kiran Godse, Nimmagadda Dheeraj Rao, Maryam Khoshkhui, Sahar Rastgoo, Roberta F. J. Criado, Mohamed Abuzakouk, Deepa Grandon, Martijn B. A. Van Doorn, Solange Oliveira Rodrigues Valle, Eduardo Magalhães De Souza Lima, Simon Francis Thomsen, German D. Ramón, Edgar E. Matos Benavides, Andrea Bauer, Ana M. Giménez‐Arnau, Emek Kocatürk, Carole Guillet, Jose Ignacio Larco, Zuo‐Tao Zhao, Michael Makris, Carla Ritchie, Paraskevi Xepapadaki, Luis Felipe Ensina, Sofia Cherrez, and Marcus Maurer
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apps ,chronische induzierbare urtikaria ,chronische spontane urtikaria ,chronische urtikaria ,UCARE ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Information/communication technologies such as mobile phone applications (apps) would enable chronic urticaria (CU) patients to self‐evaluate their disease activity and control. Yet, recently Antó et al (2021) reported a global paucity of such apps for patients with CU. In this analysis, we assessed patient interest in using apps to monitor CU disease activity and control using questions from the chronic urticaria information and communication technologies (CURICT) study. Methods The methodology for CURICT has been reported. Briefly, a 23‐item questionnaire was completed by 1841 CU patients from 17 UCAREs across 17 countries. Here, we analyzed patient responses to the CURICT questions on the use of apps for urticaria‐related purposes. Results As previously published, the majority of respondents had chronic spontaneous urticaria (CSU; 63%; 18% chronic inducible urticaria (CIndU) [CIndu]; 19% with both), were female (70%) and in urban areas (75%). Over half of patients were very/extremely interested in an app to monitor disease activity (51%) and control (53%), while only ∼1/10 were not. Patients with both urticaria types versus those with CSU only (odds ratio [OR], 1.36 [1.03–1.79]) and females versus males (OR [95% CI], 1.47 [1.17–1.85]) were more likely to be very to extremely interested in an app to assess disease control. Conclusions Overall, half of the patients with CU were very to extremely interested in using an app to assess their disease activity and control. Development of well‐designed apps, specific to disease types (CSU, CIndU, CSU + CIndU, etc), validated by experts across platforms would help improve the management and possibly outcomes of CU treatment while providing important patient information to be used in future research.
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- 2021
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19. How are patients with chronic urticaria interested in using information and communication technologies to guide their healthcare? A UCARE study
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Ivan Cherrez-Ojeda, Emanuel Vanegas, Annia Cherrez, Miguel Felix, Karsten Weller, Markus Magerl, Rasmus Robin Maurer, Valeria L. Mata, Alicja Kasperska-Zajac, Agnieszka Sikora, Daria Fomina, Elena Kovalkova, Kiran Godse, Nimmagadda Dheeraj Rao, Maryam Khoshkhui, Sahar Rastgoo, Roberta FJ. Criado, Mohamed Abuzakouk, Deepa Grandon, Martijn B.A. Van Doorn, Solange Oliveira Rodrigues Valle, Eduardo Magalhães De Souza Lima, Simon Francis Thomsen, German D. Ramón, Edgar E. Matos Benavides, Andrea Bauer, Ana M. Giménez-Arnau, Emek Kocatürk, Carole Guillet, Jose Ignacio Larco, Zuo-Tao Zhao, Michael Makris, Carla Ritchie, Paraskevi Xepapadaki, Luis Felipe Ensina, Sofia Cherrez, and Marcus Maurer
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Chronic urticaria ,Information and communication technologies ,Internet ,e-mail ,WhatsApp ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Patients with chronic urticaria (CU) are increasingly using information and communication technologies (ICTs) to manage their health. What CU patients expect from ICTs and which ICTs they prefer remains unknown. We assessed why CU patients use ICTs, which ones they prefer, and what drives their expectations and choices. Methods: In this cross-sectional study, 1841 patients across 17 countries were recruited at UCAREs (Urticaria Centers of Reference and Excellence). Patients with CU who were >12 years old completed a 23-item questionnaire. Results: Most patients were interested in receiving disease information (87.3%), asking physicians about CU (84.1%), and communicating with other patients through ICTs (65.6%). For receiving disease information, patients preferred one-to-one and one-to-many ICTs, especially web browsers. One-to-one ICTs were also the ICTs of choice for asking physicians about urticaria and for communicating with other patients, and e-mail and WhatsApp were the preferred ICTs, respectively. Many-to-many ICTs such as Facebook, Instagram, LinkedIn, and Twitter were least preferred for all 3 purposes. Living in rural areas and higher education were linked to higher odds of being interested in receiving disease information, asking physicians, and communicating with patients through ICTs. Conclusions: Most patients and especially patients with higher education who live in rural areas are interested in using ICTs for their healthcare, but prefer different ICTs for different purposes, ie, web browsers for obtaining information, e-mail for asking physicians, and WhatsApp for communicating with other patients. Our findings may help to improve ICTs for CU.
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- 2021
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20. Correction to: Long-term health-related quality of life in patients treated with subcutaneous C1-inhibitor replacement therapy for the prevention of hereditary angioedema attacks: findings from the COMPACT open-label extension study
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William R. Lumry, Bruce Zuraw, Marco Cicardi, Timothy Craig, John Anderson, Aleena Banerji, Jonathan A. Bernstein, Teresa Caballero, Henriette Farkas, Richard G. Gower, Paul K. Keith, Donald S. Levy, H. Henry Li, Markus Magerl, Michael Manning, Marc A. Riedl, John-Philip Lawo, Subhransu Prusty, Thomas Machnig, Hilary Longhurst, and the COMPACT Investigators
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Medicine - Published
- 2021
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21. The usage, quality and relevance of information and communications technologies in patients with chronic urticaria: A UCARE study
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Marcus Maurer, Karsten Weller, Markus Magerl, Rasmus Robin Maurer, Emanuel Vanegas, Miguel Felix, Annia Cherrez, Valeria L. Mata, Alicja Kasperska-Zajac, Agnieszka Sikora, Daria Fomina, Elena Kovalkova, Kiran Godse, Nimmagadda Dheeraj Rao, Maryam Khoshkhui, Sahar Rastgoo, Roberta Fachini Jardim Criado, Mohamed Abuzakouk, Deepa Grandon, Martijn van Doorn, Solange Olliveira Rodrigues Valle, Eduardo Magalhães de Souza Lima, Simon Francis Thomsen, German D. Ramón, Edgar E. Matos Benavides, Andrea Bauer, Ana Maria Giménez-Arnau, Emek Kocatürk, Carole Guillet, Jose Ignacio Larco, Zuo-Tao Zhao, Michael Makris, Carla Ritchie, Paraskevi Xepapadaki, Luis Felipe Ensina, Sofia Cherrez, and Ivan Cherrez-Ojeda
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(3–5) ICT ,Information and communications technology ,Urticaria ,Self-management ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Chronic urticaria (CU) is characterized by itchy recurrent wheals, angioedema, or both for 6 weeks or longer. CU can greatly impact patients' physical and emotional quality of life. Patients with chronic conditions are increasingly seeking information from information and communications technologies (ICTs) to manage their health. The objective of this study was to assess the frequency of usage and preference of ICTs from the perspective of patients with CU. Methods: In this cross-sectional study, 1800 patients were recruited from primary healthcare centers, university hospitals or specialized clinics that form part of the UCARE (Urticaria Centers of Reference and Excellence) network throughout 16 countries. Patients were >12 years old and had physician-diagnosed chronic spontaneous urticaria (CSU) or chronic inducible urticaria (CIndU). Patients completed a 23-item questionnaire containing questions about ICT usage, including the type, frequency, preference, and quality, answers to which were recorded in a standardized database at each center. For analysis, ICTs were categorized into 3 groups as follows: one-to-one: SMS, WhatsApp, Skype, and email; one-to-many: YouTube, web browsers, and blogs or forums; many-to-many: Instagram, Twitter, Facebook, and LinkedIn. Results: Overall, 99.6% of CU patients had access to ICT platforms and 96.7% had internet access. Daily, 85.4% patients used one-to-one ICT platforms most often, followed by one-to-many ICTs (75.5%) and many-to-many ICTs (59.2%). The daily ICT usage was highest for web browsers (72.7%) and WhatsApp (70.0%). The general usage of ICT platforms increased in patients with higher levels of education. One-to-many was the preferred ICT category for obtaining general health information (78.3%) and for CU-related information (75.4%). A web browser (77.6%) was by far the most commonly used ICT to obtain general health information, followed by YouTube (25.8%) and Facebook (16.3%). Similarly, for CU-specific information, 3 out of 4 patients (74.6%) used a web browser, 20.9% used YouTube, and 13.6% used Facebook. One in 5 (21.6%) patients did not use any form of ICT for obtaining information on CU. The quality of the information obtained from one-to-many ICTs was rated much more often as very interesting and of good quality for general health information (53.5%) and CU-related information (51.5%) as compared to the other categories. Conclusions: Usage of ICTs for health and CU-specific information is extremely high in all countries analyzed, with web browsers being the preferred ICT platform.
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- 2020
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22. Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey
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Andrea Zanichelli, Markus Magerl, Hilary J. Longhurst, Werner Aberer, Teresa Caballero, Laurence Bouillet, Anette Bygum, Anete S. Grumach, Jaco Botha, Irmgard Andresen, Marcus Maurer, and the IOS Study Group
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Hereditary angioedema ,HAE ,C1-INH-HAE ,Diagnosis ,Delay in diagnosis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.
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- 2018
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23. Epidemiology of Bradykinin-mediated angioedema: a systematic investigation of epidemiological studies
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Emel Aygören-Pürsün, Markus Magerl, Andreas Maetzel, and Marcus Maurer
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Angioedema ,Bradykinin ,Epidemiology ,C1-inhibitor ,ACE-inhibitor ,Medicine - Abstract
Abstract Background Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management. Methods We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria. Results We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark. Conclusions Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.
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- 2018
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24. An open-label study to evaluate the long-term safety and efficacy of lanadelumab for prevention of attacks in hereditary angioedema: design of the HELP study extension
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Marc A. Riedl, Jonathan A. Bernstein, Timothy Craig, Aleena Banerji, Markus Magerl, Marco Cicardi, Hilary J. Longhurst, Mustafa M. Shennak, William H. Yang, Jennifer Schranz, Jovanna Baptista, and Paula J. Busse
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Hereditary angioedema ,Lanadelumab ,Monoclonal antibody ,Bradykinin ,Plasma kallikrein ,Prophylaxis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo-controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. Methods/design The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study (“rollover patients”) and those who did not participate in the double-blind study (“non-rollover patients”), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient’s first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non-rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Discussion Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT02741596
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- 2017
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25. Abstracts from the 10th C1-inhibitor deficiency workshop
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Alvin H. Schmaier, Marco Cicardi, Avner Reshef, Dumitru Moldovan, Attila Mócsai, Margarita López-Trascasa, Alberto López Lera, Nancy J. Brown, Anastasios E. Germenis, Rafael Filippelli-Silva, Diego A. Duarte, Renan P. Martin, Camila L. Veronez, Michel Bouvier, Michael Bader, Claudio M. Costa-Neto, João Bosco Pesquero, Xavier Charest-Morin, François Marceau, Georges-É. Rivard, Arnaud Bonnefoy, Éric Wagner, Márta L. Debreczeni, Zsuzsanna Németh, Erika Kajdácsi, Endre Schwaner, László Cervenak, Gábor Oroszlán, András Szilágyi, Ráhel Dani, Péter Závodszky, Péter Gál, József Dobó, Jacques Hébert, Matthieu Vincent, Jean-Nicolas Boursiquot, Hugo Chapdeleine, Marylin Desjardins, Benoit Laramée, Rémi Gagnon, Nancy Payette, Oleksandra Lepeshkina, Delphine Charignon, Arije Ghannam, Denise Ponard, Christian Drouet, Kusumam Joseph, Baby G. Tholanikunnel, Daniel J. Sexton, Allen P. Kaplan, Stefania Loffredo, Maria Bova, Anne Lise Ferrara, Angelica Petraroli, Chiara Suffritti, Nóra Veszeli, Andrea Zanichelli, Henriette Farkas, Gianni Marone, Samuel Luyasu, Bertrand Favier, Ludovic Martin, Kinga Viktória Kőhalmi, György Temesszentandrási, Katalin Várnai, Lilian Varga, Bruce L. Zuraw, Annette Feussner, Michael A. Tortorici, Dipti Pawaskar, Huamin Henry Li, John Anderson, Jonathan A. Bernstein, Ying Zhang, Ingo Pragst, on behalf of COMPACT investigators, Emel Aygören-Pürsün, Kraig Jacobson, Jim Christensen, Arthur Van Leerberghe, Yi Wang, Jennifer Schranz, Inmaculada Martinez-Saguer, Daniel Soteres, Urs Steiner, Vesna Grivcheva Panovska, William Rae, Werner Aberer, Aarnoud Huissoon, Anette Bygum, Markus Magerl, Jochen Graff, Hilary Longhurst, Ramón Lleonart, Lei Fang, Melanie Cornpropst, Desiree Clemons, Amanda Mathis, Phil Collis, Sylvia Dobo, William P. Sheridan, Marcus Maurer, Marc A. Riedl, Timothy Craig, Aleena Banerji, Mustafa Shennak, William Yang, Jovanna Baptista, Paula Busse, Ira Kalfus, Andrew McDonald, Shawn Qian, Anthony Roberts, Con Panousis, Tim Green, Andreas Gille, Maria Zamanakou, Gedeon Loules, Dorottya Csuka, Fotis Psarros, Faidra Parsopoulou, Matthaios Speletas, Davide Firinu, Tiziana Maria Angela De Pasquale, Alessandra Zoli, Anna Radice, Stefano Pizzimenti, Emmanouil Manoussakis, George N. Konstantinou, Valeria Bafunno, Vincenzo Montinaro, Mauro Cancian, Maurizio Margaglione, Konrad Bork, Karin Wulff, Guenther Witzke, Jochen Hardt, Laurence Bouillet, Teresa Caballero, Anete S. Grumach, Christelle Pommie, Irmgard Andresen, Carmen Escuriola Ettingshausen, Zeynep Gutowski, Karin Andritschke, Richard Linde, Noémi Andrási, Tamás Szilágyi, Iris Leibovich-Nassi, Christine Symons, John Dempster, Isabelle Boccon-Gibod, Anne Pagnier, Audrey Lehmann, Kristian B. Kreiberg, Sandra A. Nieto, Raquel Martins, Renata Martins, Alejandra Menendez, Solange O. R. Valle, Margarita Olivares, Maria E. Hernandez-Landeros, Elma Nievas, Natalia Fili, Olga M. Barrera, René Bailleau, Ana Maria Gallardo-Olivos, Masumi Grau, Julian Rodriguez-Galindo, Marlon J. O. Carabantes, Edison Zapata-Venegas, Mario Martinez Alfonso, Maria Rosario-Grauert, Manuel Ratti, Daniel Vaszquez, Dario Josviack, Luis Fernando Landivar-Salinas, Oscar M. E. Calderón-Llosa, Rolando Campilay-Sarmiento, Pablo Raby, Jose Fabiani, William R. Lumry, Henrike Feuersenger, Douglas J. Watson, Thomas Machnig, on behalf of the Investigators of the COMPACT study, Donatella Lamacchia, Adriana Hernanz, Ana Alvez, Mariana Lluncor, Maria Pedrosa, Rosario Cabañas, Nieves Prior, Patrik Nordenfelt, Mats Nilsson, Anders Lindfors, Carl-Fredrik Wahlgren, Janne Björkander, Roman Hakl, Pavel Kuklínek, Irena Krčmová, Jana Hanzlíková, Martina Vachová, Radana Zachová, Marta Sobotková, Jana Strenková, Jiří Litzman, Maria Palasopoulou, Gerasimina Tsinti, Panagiota Gianni, Maria Kompoti, Sofia Garrido, Wojciech Dyga, Anna Bogdali, Aleksander Obtułowicz, Mikolajczyk Tomasz, Ewa Czarnobilska, Krystyna Obtulowicz, Teofila Książek, Anna Koncz, Dominik Gulyás, Maria Staevska, Milos Jesenak, Katarina Hrubiskova, L. Bellizzi, A. Relan, Maddalena A. Wu, Antonio Castelli, Riccardo Colombo, Gianmarco Podda, Marta Del Medico, Emanuele Catena, Francesco Casella, Francesca Perego, Nada Afifi Afifi, Eleonora Tobaldini, Nicola Montano, for the IOS Study Group, Marta Sánchez-Jareño, Marcin Stobiecki, Krystyna Obtułowicz, Irina Guryanova, Ekaterina Polyakova, Viktar Lebedz, Andrej Salivonchik, Svetlana Aleshkevich, Mikhail Belevtsev, Melanie Nordmann-Kleiner, Susanne Trainotti, Janina Hahn, Jens Greve, Liudmyla Zabrodska, Maria L. Oliva Alonso, Rosangela P. Tórtora, Alfeu T. França, Marcia G. Ribeiro, Lisa Fu, Amin Kanani, Gina Lacuesta, Susan Waserman, Stephen Betschel, Melissa I. Espinosa, Francisco A. Contreras, Martin Hrubisko, Ludmila Vavrova, Peter Banovcin, Maryam Ayazi, Mohammad Reza Fazlollahi, Shiva Saghafi, Sajedeh Mohammadian, Susan Nabilou Deshiry, Kiana Bidad, Raheleh Shokouhi Shoormasti, Iraj Mohammadzadeh, Mohammad Hassan Bemanian, Seyed Alireza Mahdaviani, Zahra Pourpak, Anna Valerieva, Mariela Vasileva, Tsvetelina Velikova, Elena Petkova, Vasil Dimitrov, Ruggero Di Maulo, on behalf of participating centers, Raz Somech, Hava Golander, Erika J. Sifuentes, Catherine Mansard, Anne Gompel, Bernard Floccard, Claire Blanchard-Delaunay, David Launay, Olivier Fain, Alain Sobel, Stéphane Gayet, Stéphanie Amarger, Guillaume Armengol, Yann Ollivier, Ariane Zélinsky-Gurung, Pierre-Yves Jeandel, Gisèle Kanny, Brigitte Coppéré, Marie Dubrel, Fabien Pelletier, Aurélie Du Thanh, Sébastien Trouiller, Jérôme Laurent, Claire De Moreuil, Christine Audouin Pajot, Alexandre Belot, Ana Rodríguez, Dasha Roa, Alicia Prieto, Maria Luisa Baeza, Borislava Krusheva, Stephanie K. A. Almeida, Rosemeire N. Constantino-Silva, Nyla Melo, Joanna Araujo Simoes, Sandra Mitie U. Palma, Jane da Silva, Bruna F. de Azevedo, Eli Mansour, Teresa González-Quevedo, Carmen Marcos, Teófilo Lobera, Blanca Sáenz de San Pedro, Ernie Avilla, Jacquie Badiou, Karen Binkley, Rozita Borici-Mazi, Linda Howlett, Paul K. Keith, Anne Rowe, Peter Waite, Aurore Billebeau, Isabelle Boccon-Gibbod, Kristina Lis, Yael Laitman, Eitan Friedman, N. M. Gokmen, O. Gulbahar, H. Onay, Z. P. Koc, and A. Z. Sin
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2017
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26. Correction to: A Germany-wide survey study on the patient journey of patients with hereditary angioedema
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Markus Magerl, Holger Gothe, Simon Krupka, Anja Lachmann, and Christoph Ohlmeier
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Medicine - Abstract
An amendment to this paper has been published and can be accessed via the original article.
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- 2021
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27. Efficacy and Safety of an Intravenous C1-Inhibitor Concentrate for Long-Term Prophylaxis in Hereditary angioedema
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Timothy Craig D.O., Ralph Shapiro M.D., Arthur Vegh M.D., James W. Baker M.D., Jonathan A. Bernstein M.D., Paula Busse M.D., Markus Magerl M.D., Inmaculada Martinez-Saguer M.D., Marc A. Riedl M.D., William Lumry M.D., Debora Williams-Herman M.D., Jonathan Edelman M.D., Henrike Feuersenger Ph.D., Thomas Machnig M.D., and Mikhail Rojavin Ph.D.
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Otorhinolaryngology ,RF1-547 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background The plasma-derived, pasteurized, nanofiltered C1-inhibitor concentrate (pnfC1-INH) is approved in the United States as an intravenous (IV) on-demand treatment for hereditary angioedema (HAE) attacks, and, in Europe, as on demand and short-term prophylaxis. Objective This analysis evaluated Berinert Patient Registry data regarding IV pnfC1-INH used as long-term prophylaxis (LTP). Methods The international registry (2010–2014) collected prospective and retrospective usage, dosing, and safety data on individuals who used pnfC1-INH for any reason. Results The registry included data on 47 subjects (80.9% female subjects; mean age, 44.8 years), which reflected 4082 infusions categorized as LTP and a total of 430.2 months of LTP administration. The median absolute dose of pnfC1-INH given for LTP was 1000 IU (range, 500–3000 IU), with a median time interval between infusion and a subsequent pnfC1-INH–treated attack of 72.0 hours (range, 0.0–166.4 hours). Fifteen subjects (31.9%) had no pnfC1-INH–treated HAE attacks within 7 days after pnfC1-INH infusion for LTP; 32 subjects (68.1%) experienced 246 attacks, with rates of 0.06 attacks per infusion and 0.57 attacks per month. A total of 81 adverse events were reported in 16 subjects (34.0%) (0.02 events per infusion; 0.19 events per month); only 3 adverse events were considered related to pnfC1-INH (noncardiac chest pain, postinfusion headache, deep vein thrombosis in a subject with an IV port). Conclusion In this international registry, IV pnf-C1-INH given as LTP for HAE was safe and efficacious, with a low rate of attacks that required pnfC1-INH treatment, particularly within the first several days after LTP administration.
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- 2017
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28. Expert Perspectives on Hereditary Angioedema: Key Areas for Advancements in Care across the Patient Journey
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Aleena Banerji M.D., Murat Baş M.D., Jonathan A. Bernstein M.D., Isabelle Boccon-Gibod M.D., Maria Bova M.D., Ph.D., John Dempster, Anete Sevciovic Grumach M.D., Ph.D., Markus Magerl M.D., Kimberly Poarch PA-C, and Manuel Branco Ferreira M.D., Ph.D.
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Otorhinolaryngology ,RF1-547 ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background Published literature documents the substantial burden of hereditary angioedema (HAE) with C1 inhibitor deficiency on the quality of life and work productivity of patients. However, despite advances in the field and the availability of guidelines to advise health care providers (HCP) on the diagnosis and management of HAE, there are still many challenges to overcome. For example, delayed diagnosis and misdiagnosis are common, and treatment practices vary worldwide. Objective An international expert panel was convened to consider opportunities for improvements that would benefit patients with HAE. Methods Based on professional and personal experiences, the experts developed schematics to describe the journey of patients through the following stages: (1) onset of symptoms and initial evaluation; (2) referral/diagnosis; and (3) management of HAE. More importantly, the panel identified key areas in which it was possible to optimize the support provided to patients and HCPs along this journey. Results Overall, this approach highlighted the need for wider dissemination of algorithms and scientific data to more effectively educate HCPs from multiple disciplines and the need for more research to inform appropriate treatment decisions. Furthermore, HAE awareness campaigns, accurate online information, and referral to patient advocacy groups were all considered helpful approaches to support patients. Conclusion More detailed and widespread information on the diagnosis and management of HAE is needed and may lead to advancements in care throughout the journey of the patient with HAE.
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- 2016
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29. WAO Guideline for the Management of Hereditary Angioedema
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Timothy Craig, DO, Emel Aygören Pürsün, MD, Konrad Bork, MD, Tom Bowen, MD, Henrik Boysen, Henriette Farkas, MD PhD, Anete Grumach, MD PhD, Constance H. Katelaris, MB BS PhD, Richard Lockey, MD, Hilary Longhurst, MD, William Lumry, MD, Markus Magerl, MD, Immaculada Martinez-Saguer, MD PhD, Bruce Ritchie, MD, Alexander Nast, MD, Ruby Pawankar, MD PhD, Bruce Zuraw, MD, and Marcus Maurer, MD
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Hereditary Angioedema (HAE) is a rare disease and for this reason proper diagnosis and appropriate therapy are often unknown or not available for physicians and other health care providers. For this reason we convened a group of specialists that focus upon HAE from around the world to develop not only a consensus on diagnosis and management of HAE, but to also provide evidence based grades, strength of evidence and classification for the consensus. Since both consensus and evidence grading were adhered to the document meets criteria as a guideline. The outcome of the guideline is to improve diagnosis and management of patients with HAE throughout the world and to help initiate uniform care and availability of therapies to all with the diagnosis no matter where the residence of the individual with HAE exists. Keywords: Hereditary Angioedema, Guidelines, HAE, therapy, management, diagnosis, medications, international
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- 2012
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30. Efficacy and safety of garadacimab, a factor XIIa inhibitor for hereditary angioedema prevention (VANGUARD): a global, multicentre, randomised, double-blind, placebo-controlled, phase 3 trial
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Timothy J Craig, Avner Reshef, H Henry Li, Joshua S Jacobs, Jonathan A Bernstein, Henriette Farkas, William H Yang, Erik S G Stroes, Isao Ohsawa, Raffi Tachdjian, Michael E Manning, William R Lumry, Inmaculada Martinez Saguer, Emel Aygören-Pürsün, Bruce Ritchie, Gordon L Sussman, John Anderson, Kimito Kawahata, Yusuke Suzuki, Petra Staubach, Regina Treudler, Henrike Feuersenger, Fiona Glassman, Iris Jacobs, and Markus Magerl
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General Medicine - Published
- 2023
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31. CRUSE – What the first 100 days have taught us
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Sophia Neisinger, Bernardo Sousa Pinto, Aiste Ramanauskaite, Jean Bousquet, Karsten Weller, Martin Metz, Markus Magerl, Emek Kocatürk, Ivan Cherrez Ojeda, Ana M Gimenez-Arnau, and Marcus Maurer
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General Medicine - Published
- 2023
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32. Hereditary Angioedema: A Review of the Current and Evolving Treatment Landscape
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Stephen D. Betschel, Aleena Banerji, Paula J. Busse, Danny M. Cohn, and Markus Magerl
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Immunology and Allergy - Published
- 2023
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33. An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema : a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trial
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Emel Aygören-Pürsün, Andrea Zanichelli, Danny M Cohn, Mauro Cancian, Roman Hakl, Tamar Kinaciyan, Markus Magerl, Inmaculada Martinez-Saguer, Marcin Stobiecki, Henriette Farkas, Sorena Kiani-Alikhan, Vesna Grivcheva-Panovska, Jonathan A Bernstein, H Henry Li, Hilary J Longhurst, Paul K Audhya, Michael D Smith, Christopher M Yea, Andreas Maetzel, Daniel K Lee, Edward P Feener, Richard Gower, William R Lumry, Aleena Banerji, Marc A Riedl, Marcus Maurer, Vascular Medicine, ACS - Atherosclerosis & ischemic syndromes, and Amsterdam Cardiovascular Sciences
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General Medicine - Abstract
Background: Guidelines recommend effective on-demand therapy for all individuals with hereditary angioedema. We aimed to assess the novel oral plasma kallikrein inhibitor, sebetralstat, which is in development, for on-demand treatment of hereditary angioedema attacks. Methods: In this two-part phase 2 trial, individuals with type 1 or 2 hereditary angioedema aged 18 years or older were recruited from 25 sites, consisting of specialty outpatient centres, across nine countries in Europe and the USA. Individuals were eligible if they had experienced at least three hereditary angioedema attacks in the past 93 days, were not on prophylactic therapy, and had access to and the ability to self-administer conventional attack treatment. In part 1 of the trial, participants were given a single 600 mg open-label oral dose of sebetralstat to assess safety, pharmacokinetics, and pharmacodynamics of the dose. Part 2 was a randomised, double-blind, placebo-controlled, two-sequence, two-period (2 × 2) crossover trial; participants were randomly assigned (1:1) to either sequence 1, in which they were given a single dose of 600 mg of sebetralstat to treat the first eligible attack and a second dose of placebo to treat the second eligible attack, or sequence 2, in which they were given placebo to treat the first eligible attack and then 600 mg of sebetralstat to treat the second eligible attack. Participants and investigators were masked to treatment assignment. The primary endpoint was time to use of conventional attack treatment within 12 h of study drug administration, which was assessed in all participants who were randomly assigned to treatment and who received study drug for two attacks during part 2 of the study. Safety was assessed in all participants who received at least one dose of study drug, starting in part 1. This study is registered with ClinicalTrials.gov, NCT04208412, and is completed. Findings: Between July 2, 2019, and Dec 8, 2020, 84 individuals were screened and 68 were enrolled in part 1 and received sebetralstat (mean age 38·3 years [SD 13·2], 37 [54%] were female, 31 [46%] were male, 68 [100%] were White). 42 (62%) of 68 participants completed pharmacokinetic assessments. Sebetralstat was rapidly absorbed, with a geometric mean plasma concentration of 501 ng/mL at 15 min. In a subset of participants (n=6), plasma samples obtained from 15 min to 4 h after study drug administration had near-complete protection from ex vivo stimulated generation of plasma kallikrein and cleavage of high-molecular-weight kininogen. In part 2, all 68 participants were randomly assigned to sequence 1 (n=34) or sequence 2 (n=34). 53 (78%) of 68 participants treated two attacks (25 [74%] in the sequence 1 group and 28 [82%] in the sequence 2 group). Time to use of conventional treatment within 12 h of study drug administration was significantly longer with sebetralstat versus placebo (at quartile 1: >12 h [95% CI 9·6 to >12] vs 8·0 h [3·8 to >12]; p=0·0010). There were no serious adverse events or adverse event-related discontinuations. Interpretation: Oral administration of sebetralstat was well tolerated and led to rapid suppression of plasma kallikrein activity, resulting in increased time to use of conventional attack treatment and faster symptom relief versus placebo. Based on these results, a phase 3 trial to evaluate the efficacy and safety of two dose levels of sebetralstat in adolescent and adult participants with hereditary angioedema has been initiated (NCT05259917). Funding: KalVista Pharmaceuticals.
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- 2023
34. Garadacimab, a Factor XIIa Inhibitor for Hereditary Angioedema Prevention (VANGUARD Study)
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Timothy Craig, Avner Reshef, Huamin Henry Li, Joshua S. Jacobs, Jonathan A. Bernstein, Henriette Farkas, William H. Yang, Erik Stroes, Isao Ohsawa, Raffi Tachdjian, Michael E. Manning, William R. Lumry, Inmaculada Martinez Saguer, Emel Aygören-Pürsün, Bruce Ritchie, Gordon L. Sussman, John Anderson, Kimito Kawahata, Yusuke Suzuki, Petra Staubach, Regina Treudler, Henrike Feuersenger, Fiona Glassman, Iris Jacobs, and Markus Magerl
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- 2023
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35. Patients with hereditary angioedema and their treatment patterns in Germany: a Delphi consensus study
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Inmaculada, Martinez-Saguer, Nina, Dominas, Ulrich, Straben, Jens, Greve, Randolf, Brehler, Markus, Magerl, Lisa M., Knipps, Jana, Knop, Amadeus, Flemming, Tino, Schubert, and Marcus, Maurer
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Delphi Technique ,Germany ,Angioedemas, Hereditary ,Quality of Life ,Humans ,Dermatology ,Complement C1 Inhibitor Protein - Abstract
Little is known about how many patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) receive on-demand and/or prophylactic treatment and what their clinical features are. Here, we estimated, using Delphi-based consensus, prevalence and treatment patterns in Germany as well as patient features linked to long-term prophylaxis.Eight experts, who together treat approximately 75% of all German HAE-C1-INH patients, participated in a classic, two-round Delphi survey. Consensus was defined as agreement between at least 75% of participants.Experts agreed that an estimated 1,350 patients in Germany have HAE-C1-INH, i.e. 1.62 per 100,000. One in four patients was estimated to receive long-term prophylaxis. Patient features linked to the use of prophylactic treatment included reduced quality of life, frequent swellings and swellings that affect the upper airways, andtwo attacks per month.The rate of prophylactic treatment in Germany is low, but is expected to increase. The level of disease activity and its impact and control are and should be considered in the choice for prophylactic treatment.
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- 2022
36. Untersuchung genetischer Einflüsse auf Riechstörungen bei Patienten mit hereditärem Angioödem Typ 1 und 2
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Marcus Maurer, Heidi Olze, André Ellrich, G Pierchalla, Markus M. Nöthen, Markus Magerl, Christiane Stieber, U Förster-Ruhrmann, Sven Cichon, and Stefanie Heilmann-Heimbach
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Dermatology - Published
- 2021
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37. The characteristics and impact of pruritus in adult dermatology patients: A prospective, cross-sectional study
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Ezzat Alarbeed, Karsten Weller, Michał Steć, Marlena Hawro, Max Spindler, Marcus Maurer, Sabine Altrichter, Ola Alraboni, Martin Metz, Markus Magerl, Katarzyna Przybyłowicz, Ulrich Reidel, and Tomasz Hawro
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Adult ,Male ,medicine.medical_specialty ,Visual analogue scale ,Cross-sectional study ,Dermatology ,Disease ,Hospital Anxiety and Depression Scale ,Severity of Illness Index ,Dermatitis, Atopic ,Suicidal Ideation ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Cost of Illness ,Quality of life ,Prevalence ,medicine ,Humans ,Prospective Studies ,skin and connective tissue diseases ,Depression (differential diagnoses) ,Aged ,Aged, 80 and over ,integumentary system ,business.industry ,Pruritus ,Atopic dermatitis ,Middle Aged ,medicine.disease ,body regions ,Cross-Sectional Studies ,030220 oncology & carcinogenesis ,Chronic Disease ,Quality of Life ,Anxiety ,Female ,medicine.symptom ,business - Abstract
Background Pruritus often accompanies chronic skin diseases, exerting considerable burden on many areas of patient functioning; this burden and the features of pruritus remain insufficiently characterized. Objective To investigate characteristics, including localization patterns, and burden of pruritus in patients with chronic dermatoses. Methods We recruited 800 patients with active chronic skin diseases. We assessed pruritus intensity, localization, and further characteristics. We used validated questionnaires to assess quality of life, work productivity and activity impairment, anxiety, depression, and sleep quality. Results Nine out of every 10 patients had experienced pruritus throughout their disease and 73% in the last 7 days. Pruritus often affected the entire body and was not restricted to skin lesions. Patients with moderate to severe pruritus reported significantly more impairment to their sleep quality and work productivity, and they were more depressed and anxious than control individuals and patients with mild or no pruritus. Suicidal ideations were highly prevalent in patients with chronic pruritus (18.5%) and atopic dermatitis (11.8%). Conclusions Pruritus prevalence and intensity are very high across all dermatoses studied; intensity is linked to impairment in many areas of daily functioning. Effective treatment strategies are urgently required to treat pruritus and the underlying skin disease.
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- 2021
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38. Impact of lanadelumab on health‐related quality of life in patients with hereditary angioedema in the HELP study
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Marcus Maurer, Hannah B Lewis, Aleena Banerji, Peng Lu, Markus Magerl, Giovanna Devercelli, Gagan Jain, William R. Lumry, Karsten Weller, Marc A. Riedl, Help Study Investigators, and Hilary Longhurst
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0301 basic medicine ,medicine.medical_specialty ,lanadelumab ,Immunology ,Atopic Dermatitis, Urticaria and Skin Disease ,AE‐QoL ,Lanadelumab ,Placebo ,Antibodies, Monoclonal, Humanized ,long‐term prophylaxis ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,Internal medicine ,Surveys and Questionnaires ,medicine ,Immunology and Allergy ,Humans ,In patient ,Angioedema ,business.industry ,Minimal clinically important difference ,Angioedemas, Hereditary ,medicine.disease ,humanities ,hereditary angioedema ,030104 developmental biology ,Mood ,030228 respiratory system ,quality of life ,Hereditary angioedema ,Original Article ,medicine.symptom ,ORIGINAL ARTICLES ,business - Abstract
Background An objective of the phase 3 HELP Study was to investigate the effect of lanadelumab on health‐related quality of life (HRQoL) in patients with hereditary angioedema (HAE). Methods Patients with HAE‐1/2 received either lanadelumab 150 mg every 4 weeks (q4wks; n = 28), 300 mg q4wks (n = 29), 300 mg every 2 weeks (q2wks; n = 27), or placebo (n = 41) for 26 weeks (days 0–182). The Angioedema Quality of Life Questionnaire (AE‐QoL) was administered monthly, consisting of four domain (functioning, fatigue/mood, fears/shame, nutrition) and total scores. The generic EQ‐5D‐5L questionnaire was administered on days 0, 98, and 182. Comparisons were made between placebo and (a) all lanadelumab‐treated patients and (b) individual lanadelumab groups for changes in scores (day 0–182) and proportions achieving the minimal clinically important difference (MCID, −6) in AE‐QoL total score. Results Compared with the placebo group, the lanadelumab total group demonstrated significantly greater improvements in AE‐QoL total and domain scores (mean change, −13.0 to −29.3; p, In the phase 3 HELP Study, HRQoL (health‐related quality of life) of patients with HAE (hereditary angioedema)‐1/2 was evaluated using the angioedema‐specific AE‐QoL (Angioedema Quality of Life Questionnaire). After 26 weeks, lanadelumab‐treated patients experienced significantly greater HRQoL improvements than placebo‐treated patients. Patients receiving lanadelumab 300 mg q2wks (every 2 weeks) were most likely to see clinically meaningful benefit, with 81% reaching the MCID (minimal clinically important difference) and seven times greater odds vs placebo for this achievement. Abbreviations: AE‐QoL, Angioedema Quality of Life Questionnaire; HAE, hereditary angioedema; HRQoL, health‐related quality of life; MCID, minimal clinically important difference; q2wks, every 2 weeks; q4wks, every 4 weeks.
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- 2020
39. A novel deep intronic SERPING1 variant as a cause of hereditary angioedema due to C1-inhibitor deficiency
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Faidra Parsopoulou, Grzegorz Porebski, Anna Valerieva, Krystyna Obtułowicz, Anastasios E. Germenis, Sofia Vatsiou, Gedeon Loules, Marcus Maurer, Maria Zamanakou, Matthaios Speletas, Markus Magerl, Henriette Farkas, Dorottya Csuka, Maria Staevska, and Fotis Psarros
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lcsh:Immunologic diseases. Allergy ,Genotype ,Intronic mutations ,Genomics ,Biology ,DNA sequencing ,C1-inhibitor deficiency ,Loss of heterozygosity ,symbols.namesake ,Gene Frequency ,Humans ,Immunology and Allergy ,Coding region ,Genetic Predisposition to Disease ,Allele ,Alleles ,Genetics ,Sanger sequencing ,Hereditary angioedema ,Angioedemas, Hereditary ,intronic mutations ,Computational Biology ,High-Throughput Nucleotide Sequencing ,General Medicine ,Introns ,hereditary angioedema ,Minor allele frequency ,Mutation ,Mutation (genetic algorithm) ,symbols ,Next-generation sequencing ,SERPING1 gene ,next-generation sequencing ,lcsh:RC581-607 ,Complement C1 Inhibitor Protein - Abstract
Background In about 5% of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) no mutation in the SERPING1 gene is detected. Methods C1-INH-HAE cases with no mutation in the coding region of SERPING1 after conventional genotyping were examined for defects in the intronic or untranslated regions of the gene. Using a next-generation sequencing (NGS) platform targeting the entire SERPING1, 14 unrelated C1-INH-HAE patients with no detectable mutations in the coding region of the gene were sequenced. Detected variants with a global minor allele frequency lower than the frequency of C1-INH-HAE (0.002%), were submitted to in silico analysis using ten different bioinformatics tools. Pedigree analysis and examination of their pathogenic effect on the RNA level were performed for filtered in variants. Results In two unrelated patients, the novel mutation c.-22-155G > T was detected in intron 1 of the SERPING1 gene by the use NGS and confirmed by Sanger sequencing. All bioinformatics tools predicted that the variant causes a deleterious effect on the gene and pedigree analysis showed its co-segregation with the disease. Degradation of the mutated allele was demonstrated by the loss of heterozygosity on the cDNA level. According to the American College of Medical Genetics and Genomics 2015 guidelines the c.-22-155G > T was curated as pathogenic. Conclusions For the first time, a deep intronic mutation that was detected by NGS in the SERPING1 gene, was proven pathogenic for C1-INH-HAE. Therefore, advanced DNA sequencing methods should be performed in cases of C1-INH-HAE where standard approaches fail to uncover the genetic alteration.
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- 2020
40. Cool bleiben beim akuten Angioödem
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Thomas Buttgereit and Markus Magerl
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medicine.medical_specialty ,business.industry ,medicine ,business ,Dermatology - Published
- 2020
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41. Development of the Angioedema Control Test—A patient‐reported outcome measure that assesses disease control in patients with recurrent angioedema
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Torsten Zuberbier, Denise Freier, Marcus Maurer, Frank Siebenhaar, Karoline Krause, Martin Metz, Tamara Donoso, Emel Aygören-Pürsün, Petra Staubach, Sabine Altrichter, Karsten Weller, Inmaculada Martinez-Saguer, Markus Magerl, and Tomasz Hawro
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0301 basic medicine ,medicine.medical_specialty ,Immunology ,Validity ,Context (language use) ,Bradykinin ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Content validity ,Humans ,Immunology and Allergy ,Patient Reported Outcome Measures ,Angioedema ,Retrospective Studies ,Recall ,business.industry ,Reproducibility of Results ,medicine.disease ,Disease control ,030104 developmental biology ,030228 respiratory system ,Hereditary angioedema ,Physical therapy ,Patient-reported outcome ,medicine.symptom ,business - Abstract
Background Recurrent angioedema (AE) is an important clinical problem in the context of chronic urticaria (mast cell mediator-induced), ACE-inhibitor intake and hereditary angioedema (both bradykinin-mediated). To help patients obtain control of their recurrent AE is a major treatment goal. However, a tool to assess control of recurrent AE is not yet available. This prompted us to develop such a tool, the Angioedema Control Test (AECT). Methods After a conceptional framework was developed for the AECT, a list of potential AECT items was generated by a combined approach of patient interviews, literature review and expert input. Subsequent item reduction was based on impact analysis, inter-item correlation, additional predefined criteria for item performance, and a review of the item selection process for content validity. Finally, an instruction section was generated, and an US-American-English version was developed by a structured translation process. Results A 4-item AECT with recall periods of 4 weeks and 3 months was developed based on 106 potential items tested in 97 patients with mast cell mediator-induced (n = 49) or bradykinin-mediated recurrent AE (n = 48). Eighty-four items were excluded based on impact analysis. The remaining 22 items could be further reduced by a method-mix of inter-item correlation, additional predefined criteria for item performance and review for content validity. Conclusions The AECT is the first tool to assess disease control in recurrent AE patients. Its retrospective approach, its brevity and its simple scoring make the AECT ideally suited for clinical practice and trials. Its validity and reliability need to be determined in future independent studies.
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- 2020
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42. International Consensus on the Use of Genetics in the Management of Hereditary Angioedema
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Jose Fabiani, Emel Aygören-Pürsün, Sladjana Andrejevic, Christian Drouet, Nóra Veszeli, Matija Rijavec, Georg Dewald, Markus Magerl, Michael Kirschfink, Marco Cicardi, Camila Lopes Veronez, Imola Beatrix Nagy, Massimo Triggiani, Maria Zamanakou, Henrik Halle Boysen, Matthaios Speletas, Maria Bova, Maria Staevska, Maurizio Margaglione, Sandra C. Christiansen, Teresa Caballero, Milos Jesenak, Vesna Grivcheva-Panovska, Allen P. Kaplan, Kinga Viktoria Köhalmi, Anthony J. Castaldo, Roman Hakl, Gaëlle Hardy, Walter A. Wuillemin, Inmaculada Martinez Saguer, Margarita López Trascasa, João Bosco Pesquero, Sven Cichon, Jonathan A. Bernstein, Grzegorz Porebski, Patrik Nordenfelt, C. Katelaris, Anette Bygum, Maria Teresa Gonzalez-Quevedo, Stephen Jolles, Henriette Farkas, Sandra A. Nieto, William R. Lumry, Hilary Longhurst, Spath Peter, Iris Leibovich, Nihal M. Gökmen, Christina Weber, Noemi-Anna Bara, Konrad Bork, Alberto López Lera, Dorottya Csuka, Fotis Psarros, Laurence Bouillet, Marc A. Riedl, Bruce L. Zuraw, Anete Sevciovic Grumach, Farrukh R. Sheikh, Marcin Stobiecki, Anastasios E. Germenis, Ágnes Szilágyi, Avner Reshef, Susan Waserman, and J. Gooi
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Consensus ,Genetic counseling ,Genetic Counseling ,Disease ,C1-inhibitor ,03 medical and health sciences ,0302 clinical medicine ,Genetics ,medicine ,Humans ,Immunology and Allergy ,Genetic Testing ,030212 general & internal medicine ,Angioedema ,Disease management (health) ,Genotyping ,Genetic testing ,Hereditary angioedema ,biology ,medicine.diagnostic_test ,ClinVar ,Variant pathogenicity curation ,business.industry ,Angioedemas, Hereditary ,medicine.disease ,030228 respiratory system ,biology.protein ,medicine.symptom ,business ,Complement C1 Inhibitor Protein - Abstract
Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories, and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex. With this in mind, an international multidisciplinary group of 14 experts in HAE genetics and disease management was convened in October 2018. The objective was to develop clear, actionable, evidence- and consensus-based statements aiming to facilitate the communication between physicians treating patients with HAE and clinical geneticists, and thus promote the effective use of genetics in the management of the disease. Eleven consensus statements were generated, encompassing considerations regarding the clinical indications for genotyping patients with angioedema, the methods of detection of HAE-causative variants, the variant pathogenicity curation, the genotyping of patients with HAE in the clinic, and genetic counseling. These statements are intended both to guide clinicians and to serve as a framework for future educational and further genetic testing developments as the field continues to evolve rapidly.
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- 2020
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43. The international EAACI/GA²LEN/EuroGuiDerm/APAAACI guideline for the definition, classification, diagnosis, and management of urticaria
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Corinna Dressler, Paulo Ricardo Criado, Christian Vestergaard, Alexander Kapp, Alexander Nast, Luca Stingeni, Martine Grosber, R. Y. Meshkova, Barbara Ballmer-Weber, Bettina Wedi, Aharon Kessel, Paolo D. Pigatto, Frank Siebenhaar, Jonathan A. Bernstein, Clive Grattan, Angèle Soria, Torsten Zuberbier, Andrea Szegedi, Riccardo Asero, Petra Staubach-Renz, Désirée Larenas-Linnemann, Knut Brockow, Allen P. Kaplan, Charlotte G. Mortz, Mohamed Abuzakouk, Michihiro Hide, Daniel Micallef, Margarida Gonçalo, S. Aquilina, María Isabel Rojo Gutiérrez, Herberto José Chong Neto, Gordon Sussman, Tabi A. Leslie, Aslı Gelincik, Peter Schmid-Grendelmeier, Zahava Vadasz, Amir Hamzah Abdul Latiff, Hanna Siiskonen, Markus Magerl, Simon Francis Thomsen, Eckard Hamelmann, Sarbjit S. Saini, A. Giménez-Arnau, Luis Felipe Ensina, Bulent Enis Sekerel, Hanneke Oude-Elberink, I V Danilycheva, Zenon Brzoza, Hector Ratti Sisa, Michael Makris, Kiran Godse, Jacques Hébert, Antti Lauerma, Moshe Ben-Shoshan, Luz Fonacier, Emek Kocatürk, Zuotao Zhao, Kanokvalai Kulthanan, Matthew Gaskins, Carsten Bindslev-Jensen, Diane Baker, Krisztián Gáspár, Martin K. Church, Marcus Maurer, Ruby Pawankar, Martin Metz, Christine Bangert, Groningen Research Institute for Asthma and COPD (GRIAC), Publica, Gerontology, Surgical clinical sciences, Skin function and permeability, and Dermatology
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medicine.medical_specialty ,Evidence-based practice ,hives ,media_common.quotation_subject ,Immunology ,education ,Dermatology ,Angioedema/diagnosis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,urticaria ,0302 clinical medicine ,Quality of life ,Excellence ,immune system diseases ,evidence-based ,parasitic diseases ,medicine ,Prevalence ,Immunology and Allergy ,media_common.cataloged_instance ,Humans ,itch ,European union ,skin and connective tissue diseases ,wheal ,Asthma ,media_common ,Angioedema ,business.industry ,angioedema ,Consensus conference ,GUIDELINES ,consensus ,evidence2̆010based ,mast cell ,Guideline ,medicine.disease ,3. Good health ,ddc ,030228 respiratory system ,Family medicine ,Chronic Disease ,Quality of Life ,Urticaria/diagnosis ,medicine.symptom ,business ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.
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- 2022
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44. Efficacy and Safety of Subcutaneous Garadacimab for the Prophylaxis of Hereditary Angioedema Attacks in Adults and Adolescent Patients with HAE: Results from a Multicenter, Placebo-Controlled Phase 3 Trial
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Timothy Craig, Markus Magerl, Avner Reshef, Huamin Li, Joshua Jacobs, Jonathan Bernstein, Henriette Farkas, William Yang, Erik Stroes, Isao Ohsawa, Raffi Tachdjian, Michael Manning, William Lumry, Inmaculada Martinez Saguer, Emel Aygören-Pürsün, Bruce Ritchie, Gordon Sussman, John Anderson, Kimito Kawahata, Yusuke Suzuki, Petra Staubach, Regina Treudler, Henrike Feuersenger, Lolis Wieman, and Iris Jacobs
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Immunology ,Immunology and Allergy - Published
- 2023
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45. Berotralstat Improved Quality of Life through 96 Weeks Across Multiple Subgroups of Patients with Hereditary Angioedema
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Daniel Soteres, William Lumry, Markus Magerl, Remi Gagnon, Bhavisha Desai, Dianne Tomita, Douglas Johnston, and Marcus Maurer
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Immunology ,Immunology and Allergy - Published
- 2023
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46. Efficacy And Safety Of Bradykinin B2 Receptor Inhibition With Oral PHVS416 In Treating Hereditary Angioedema Attacks: Results Of RAPIDe-1 Phase 2 Trial
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Marcus Maurer, John Anderson, Emel Aygören-Pürsün, Laurence Bouillet, María Luisa Baeza, Hugo Chapdelaine, Danny Cohn, Aurélie Du-Thanh, Olivier Fain, Henriette Farkas, Jens Greve, Mar Guilarte, David Hagin, Roman Hakl, Joshua Jacobs, Aharon Kessell, Sorena Kiani-Alikhan, Pavlína Králíčková, Huamin Li, Ramon Lleonart Bellfill, Markus Magerl, Michael Manning, Avner Reshef, Bruce Ritchie, Giuseppe Spadaro, Maria Staevska, Petra Staubach, Marcin Stobiecki, Gordon Sussman, Michael Tarzi, Anna Valerieva, William Yang, Marie-Helene Jouvin, Rafael Crabbé, Simone van Leeuwen, Huaihou Chen, Li Zhu, Jochen Knolle, Anne Lesage, Peng Lu, and Marc Riedl
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Immunology ,Immunology and Allergy - Published
- 2023
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47. Consensus on treatment goals in hereditary angioedema:a global Delphi initiative
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Anthony J. Castaldo, Anete Sevciovic Grumach, H. Henry Li, Paula J. Busse, Bruce L. Zuraw, Marc A. Riedl, Constance H. Katelaris, Inmaculada Martinez-Saguer, Yuxiang Zhi, Jonathan A. Bernstein, Anette Bygum, Henriette Farkas, Michihiro Hide, Teresa Caballero, W. Lumry, Marcus Maurer, Aleena Banerji, Emel Aygören-Pürsün, Timothy J. Craig, Markus Magerl, Hilary Longhurst, Henrik Balle Boysen, and Sandra C. Christiansen
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medicine.medical_specialty ,Consensus ,Immunology ,Delphi method ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,medicine ,Animals ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Disease management (health) ,Skin ,Hereditary angioedema ,Angioedema ,business.industry ,Angioedemas, Hereditary ,Disease Management ,acute treatment ,Guideline ,Emergency department ,C1-INH deficiency ,medicine.disease ,Treatment Outcome ,030228 respiratory system ,quality of life ,Family medicine ,Practice Guidelines as Topic ,Quality of Life ,prophylaxis ,treatment goals ,medicine.symptom ,business ,Complement C1 Inhibitor Protein - Abstract
Background: Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder characterized by recurrent episodes of subcutaneous or submucosal angioedema. The ultimate goals of treatment for HAE remain ill-defined. Objectives: The aim of this Delphi process was to define the goals of HAE treatment and to examine which factors should be considered when assessing disease control and normalization of the patient's life. Methods: The Delphi panel comprised 23 participants who were selected based on involvement with scientific research on HAE or coauthorship of the most recent update and revision of the World Allergy Organization/European Academy of Allergy and Clinical Immunology guideline on HAE. The process comprised 3 rounds of voting. The final round aimed to aggregate the opinions of the expert panel and to achieve consensus. Results: Two direct consensus questions were posed in round 2, based on the responses received in round 1, and the panel agreed that the goals of treatment are to achieve total control of the disease and to normalize the patient's life. For the third round of voting, 21 statements were considered, with the participants reaching consensus on 18. It is clear from the wide-ranging consensus statements that the burdens of disease and treatment should be considered when assessing disease control and normalization of patients’ lives. Conclusions: The ultimate goal for HAE treatment is to achieve no angioedema attacks. The availability of improved treatments and disease management over the last decade now makes complete control of HAE a realistic possibility for most patients.
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- 2021
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48. HAE patient self-sampling for biomarker establishment
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Neil Inhaber, Selen Zülbahar, Susanne Zielke, Arndt Rolfs, Volha Skrahina, Toni M Förster, Markus Magerl, Marcus Maurer, and Donatello Crocetta
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medicine.medical_specialty ,Bradykinin ,Disease ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Pandemics ,Genetics (clinical) ,Observational clinical study ,Hereditary angioedema ,Angioedema ,SARS-CoV-2 ,business.industry ,Research ,Angioedemas, Hereditary ,Genetic disorder ,COVID-19 ,Self-sampling ,Biomarker ,General Medicine ,medicine.disease ,Dried blood spot ,chemistry ,Cleaved high molecular weight Kininogen ,Medicine ,Biomarker (medicine) ,medicine.symptom ,business ,Complement C1 Inhibitor Protein ,Biomarkers ,Self sampling - Abstract
Background Hereditary Angioedema (HAE) is a genetic disorder that leads to frequent angioedema attacks in various parts of the body. In most cases it is caused by pathogenic variants in the SERPING1 gene, coding for C1-Inhibitor (C1-INH). The pathogenic variants in the gene result in reduced C1-INH levels and/or activity, which causes aberrant bradykinin production and enhanced vascular permeability. The standard-of-care diagnostic test is performed biochemically via measuring C1-INH level and activity as well as the C4 level. This, however, does not allow for the diagnosis of HAE types with normal C1-INH. There is an urgent need to identify and characterize HAE biomarkers for facilitating diagnostics and personalizing the treatment. The Hereditary Angioedema Kininogen Assay (HAEKA) study aims to measure the dynamics of cleaved High Molecular Weight Kininogen (HKa) and other metabolite levels during the angioedema and non-angioedema state of the disease. The metabolites will be analyzed and verified by liquid chromatography ion mobility high resolution mass spectrometry (LC/IM-QToF MS) of dried blood spot (DBS) cards upon the study completion. The study design is truly innovative: 100 enrolled participants provide blood samples via DBS: (1) every 3 months within 2 years during regular study site visits and (2) by at-home self-sampling during HAE attacks via finger pricking. We are presenting a project design that permits clinical study activities during pandemic contact restrictions and opens the door for other clinical studies during COVID-19. Results As of October 2020, there are 41 patients from 5 sites in Germany enrolled. 90 blood samples were collected during the regular visits, and 19 of the participants also performed self-sampling during the HAE attacks from which a total of 286 attack blood samples were collected. Participating patients rate the study procedures as easy to implement in their daily lives. The concept of home self-sampling is effective, reproducible, and convenient especially in times of contact restrictions due to the COVID-19 pandemic. Conclusions It is the hope that the HAEKA study will complete in 2023, reveal biomarker(s) for monitoring HAE disease activity, and may help to avoid HAE attacks via applying medication prior to the symptom onset.
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- 2021
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49. Attenuated androgen discontinuation in patients with hereditary angioedema: a commented case series
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Marcus Maurer, Markus Magerl, Emel Aygören-Pürsün, Konrad Bork, Henriette Farkas, Hilary Longhurst, Sorena Kiani‑Alikhan, Laurence Bouillet, Isabelle Boccon-Gibod, Mauro Cancian, Andrea Zanichelli, and David Launay
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Oxandrolone ,Prophylaxis ,Danazol ,Case Report ,General Medicine ,Angioedema, hereditary ,Immunologic diseases. Allergy ,RC581-607 ,urologic and male genital diseases ,Attenuated androgens ,Case series - Abstract
Background Hereditary angioedema (HAE) is characterized by potentially severe and life-threatening attacks of localized swelling. Prophylactic therapies are available, including attenuated androgens. Efficacy of attenuated androgens has not been assessed in large, randomized, placebo-controlled trials and can be associated with frequent, and sometimes severe, side effects. As better tolerated targeted therapies become available, attenuated androgen withdrawal is increasingly considered by physicians and their patients with HAE. Attenuated androgens withdrawal has not been systematically studied in HAE, although examination of other disorders indicates that attenuated androgen withdrawal may result in mood disturbances and flu-like symptoms. Standardized protocols for attenuated androgen discontinuation that continue to provide control of attacks while limiting potential attenuated androgen withdrawal symptoms are not established as the outcomes of different withdrawal strategies have not been compared. We aim to describe the challenges of attenuated androgen discontinuation in patients with HAE and how these may continue into the post-androgen period. Case presentation We present a retrospective case series of 10 patients with confirmed type I HAE who have discontinued prophylactic treatment with attenuated androgens. The most common reason for attenuated androgen discontinuation was side effects. Attenuated androgens were either immediately withdrawn, tapered and/or overlapped with another treatment. The major challenge of discontinuation was the management of an increased frequency and severity of HAE attacks in some patients. Conclusions Healthcare teams need to undertake careful planning and monitoring after attenuated androgens discontinuation, and modify treatment strategies if HAE control is destabilized with an increased number of attacks. Discontinuation of attenuated androgens is definitively an option in an evolving HAE treatment landscape, and outcomes can be favourable with additional patient support and education.
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- 2021
50. Mitigating Disparity in Health-care Resources Between Countries for Management of Hereditary Angioedema
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Anette Bygum, Avner Reshef, Youjia Zhong, Markus Magerl, Grzegorz Porebski, and OKAN GULBAHAR
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0301 basic medicine ,Clinical guidelines ,medicine.medical_specialty ,Medications ,Treatment goals ,Article ,Inequity ,03 medical and health sciences ,0302 clinical medicine ,Health care ,medicine ,Immunology and Allergy ,Angioedema ,Intensive care medicine ,business.industry ,Disparity ,Equity (finance) ,General Medicine ,medicine.disease ,Treatment ,030104 developmental biology ,030228 respiratory system ,Mucosal edema ,Hereditary angioedema ,medicine.symptom ,business ,Limited resources - Abstract
Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of skin and mucosal edema. The main treatment goal is to enable a “normal life” for all patients. However, due to high costs, there are limited options for the management of HAE in most developing and low-income countries. As a result, most of the recommended first-line treatments are not available. In this review, we attempt to highlight the disparities in health-care resources for the management of patients with HAE amongst different countries. Data was collected from HAE experts in countries who provide tabulated information regarding management and availability of HAE treatments in their countries. We reviewed the two most recent international HAE guidelines. Using India, the world’s second most populous country, as a paradigm for HAE management in lower-income countries, we reviewed the evidence for second-line and non-recommended practices reported by HAE experts. Results suggest significant inequities in provision of HAE services and treatments. HAE patients in low-income countries do not have access to life-saving acute drugs or recently developed highly effective prophylactic medications. Most low-income countries do not have specialized HAE services or diagnostic facilities, resulting in consequent long delays in diagnosis. Suggestions for optimizing the use of limited resources as a basis for future discussion and reaching a global consensus are provided. There is an urgent need to improve HAE services, diagnostics and treatments currently available to lower-income countries. We recommend that all HAE stakeholders support the need for global equity and access to these essential measures. Supplementary Information The online version contains supplementary material available at 10.1007/s12016-021-08854-5.
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- 2021
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