5,146 results on '"Hereditary angioedema"'
Search Results
2. Donidalorsen Expanded Access Program for Patients With Hereditary Angioedema
- Published
- 2024
3. Social Evaluated Cold Pressor Test in Hereditary Angioedema Patients (FROSEN)
- Published
- 2024
4. A Gene Therapy Study of BMN 331 in Subjects With Hereditary Angioedema (HAErmony-1)
- Published
- 2024
5. Autonomic Nervous System Profile in Hereditary Angioedema (ANS-HAE)
- Published
- 2024
6. Long-term Safety and Efficacy of CSL312 (Garadacimab) in the Prophylactic Treatment of Hereditary Angioedema Attacks
- Published
- 2024
7. Study of Oral Deucrictibant Soft Capsule for On-Demand Treatment of Angioedema Attacks in Adolescents and Adults With Hereditary Angioedema (RAPIDe-3)
- Published
- 2024
8. A Long-term Study of STAR-0215 in Participants With Hereditary Angioedema
- Published
- 2024
9. A Study of STAR-0215 in Participants With Hereditary Angioedema
- Published
- 2024
10. Patient Registry to Evaluate the Real-world Safety of Ruconest®
- Author
-
US Hereditary Angioedema Association
- Published
- 2024
11. Safety, Tolerability, PK, PD of ADX-324 in Healthy Volunteers and Hereditary Angioedema Patients
- Published
- 2024
12. Safety of Ruconest in 2-13 Year Old Hereditary Angioedema (HAE) Patients
- Published
- 2024
13. Berotralstat Treatment in Children With Hereditary Angioedema (APeX-P)
- Published
- 2024
14. NTLA-2002 in Adults With Hereditary Angioedema (HAE) (NTLA-2002)
- Published
- 2024
15. PK Subtrial in Adolescent Patients With HAE Type I or II Participating in the KVD900-302 Trial
- Published
- 2024
16. An Open-label Extension Trial to Evaluate the Long-term Safety of KVD900 for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
- Published
- 2024
17. Dose-ranging Study of Oral PHA-022121 for Prophylaxis Against Angioedema Attacks in Patients With Hereditary Angioedema Type I or Type II (HAE CHAPTER-1)
- Published
- 2024
18. A Study to Assess the Long-Term Safety and Efficacy of Donidalorsen in the Prophylactic Treatment of Hereditary Angioedema (HAE)
- Published
- 2024
19. An Extension Study of Donidalorsen (IONIS-PKK-LRx) in Participants With Hereditary Angioedema
- Published
- 2024
20. C1 Inhibitor Registry in the Treatment of Hereditary Angioedema (HAE) Attacks
- Published
- 2024
21. A Phase III, Crossover Trial Evaluating the Efficacy and Safety of KVD900 for On-Demand Treatment of Angioedema Attacks in Adolescent and Adult Patients With Hereditary Angioedema (HAE)
- Published
- 2024
22. A Study of STAR-0215 in Healthy Adult Participants
- Published
- 2024
23. OASIS-HAE: A Study to Evaluate the Safety and Efficacy of Donidalorsen (ISIS 721744 or IONIS-PKK-LRx) in Participants With Hereditary Angioedema (HAE)
- Published
- 2024
24. Uncovering a novel SERPING1 pathogenic variant: insights into the aggregation of C1-INH in hereditary angioedema.
- Author
-
Jiang, Lingxi, Dai, Chao, Duan, Suyang, Wang, Tingting, Xie, Chunbao, Zhang, Luhan, Ye, Zimeng, Ma, Xiumei, and Shi, Yi
- Abstract
Background: Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. Results: In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Conclusion: Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. DAB2IP associates with hereditary angioedema: Insights into the role of VEGF signaling in HAE pathophysiology.
- Author
-
D'Apolito, Maria, Santacroce, Rosa, Vazquez, Daniel Osvaldo, Cordisco, Giorgia, Fantini, Claudio Agustin, D'Andrea, Giovanna, Leccese, Angelica, Colia, Anna Laura, Martinez, Pablo, Zanichelli, Andrea, Josviack, Darío, and Margaglione, Maurizio
- Abstract
In the recent years, there was an important improvement in the understanding of the pathogenesis of hereditary angioedema (HAE). Notwithstanding, in a large portion of patients with unknown mutation (HAE-UNK) the genetic cause remains to be identified. To identify new genetic targets associated with HAE, a large Argentine family with HAE-UNK spanning 3 generations was studied. Whole exome sequencing was performed on affected family members to identify potential genetic variants associated with HAE-UNK. In silico analyses and experimental studies were applied to assess the role of the identified gene variant. A missense variant (p.D239N) in DAB2IP was identified. The variant occurred in the C2-domain, the region interacting with vascular endothelial growth factor receptor 2 (VEGFR2). It was found to be rare, and predicted to have a detrimental effect on the functionality of DAB2IP. Protein structure modeling predicted changes in the mutant p.D239N protein structure, impacting protein stability. The p.D239N variant affected the subcellular localization of VEGFR2. Cells transfected with the DAB2IP-239N transcript exhibited an intracellular distribution, and VEGFR2 remained associated with the cell membrane. The altered localization pattern indicated reduced colocalization of the mutant protein with VEGFR2, suggesting a diminished ability of VEGFR2 binding. The study identified a novel missense variant (p.D239N) in DAB2IP in a family with HAE-UNK and highlighted the role of dysregulated VEGF-mediated signaling in altered endothelial permeability. DAB2IP loss-of-function pathogenic variants lead to the impairment of the endothelial VEGF/VEGFR2 ligand system and represent a new pathophysiologic cause of HAE-UNK. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. A human centred innovative approach based on persona in hereditary angioedema.
- Author
-
Perego, Francesca, Zingale, Lorenza Chiara, Cesoni Marcelli, Azzurra, Ranucci, Luca, Rimoldi, Lorenzo, Nsanbayeva, Nurgul, Natale, Maria Rosaria, Dalla Vecchia, Laura Adelaide, and Gorini, Alessandra
- Subjects
- *
CAREGIVERS , *PATIENTS' families , *MEDICAL personnel , *QUALITY of life , *DISEASE management - Abstract
Background: Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients' quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals' attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients' and their caregivers' interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas. Results: We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants' personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community. Conclusion: A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. Prodromal symptoms of hereditary angioedema (HAE) attacks: A patient survey in UK and Spain.
- Author
-
Yong, Patrick F. K. and Guilarte, Mar
- Subjects
- *
PATIENT experience , *MEDICAL personnel , *PATIENTS' attitudes , *SPANIARDS , *GENETIC mutation - Abstract
This article discusses a survey conducted among 208 hereditary angioedema (HAE) patients in the UK and Spain to investigate the prodromal symptoms, or early signs and symptoms, that precede HAE attacks. The majority of patients reported experiencing prodromes before swelling occurred, with the most common symptoms being tiredness/fatigue, pressure or tightness in the skin, and abdominal pressure. The actions taken by patients at the onset of prodromal symptoms differed between countries, with UK patients more likely to self-medicate and Spanish patients more likely to wait. The study suggests that early treatment may be associated with better outcomes, but there is variability in patient behavior regarding "early treatment." Clearer communication between healthcare providers and patients is important, and further research is needed to determine the predictive value of prodromes and their relationship to HAE attacks. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
28. Centralized care model for hereditary angioedema overcomes geographical barriers.
- Author
-
Holmes, Ashley, Srinivasan, Cindy, Borle, Jack, Blain, Heather, Ritchie, Bruce, and Adatia, Adil
- Subjects
RURAL medicine ,POISSON regression ,ANGIONEUROTIC edema ,ODDS ratio ,LOGISTIC regression analysis - Abstract
Hereditary angioedema due to C1 inhibitor deficiency (HAE) is a rare inborn error of immunity that presents with episodic swelling. Management is multifaceted and includes on-demand treatment of swelling episodes, short-term prophylaxis to prevent swelling episodes from procedures, and long-term prophylaxis (LTP) to prevent angioedema on an ongoing basis. All approved on-demand therapies are parenteral, necessitating patient training for home administration, particularly intravenous C1 inhibitor. These complexities can result in care gaps for rural HAE patients. We conducted a cross-sectional study at our Angioedema Center of Reference and Excellence to assess the care provided to urban and rural patients. The proportion of patients receiving LTP, proportion of patients diagnosed as children, and disease control measured using the Angioedema Control Test (AECT) were collected. Logistic and Poisson regression models adjusted for age and sex were used to compare the two groups. The proportion using LTP was similar at 62% and 61% in urban and rural patients, respectively (odds ratio [OR] 1.01 (CI 95% 0.34-2.99)). Among urban patients, 52% were diagnosed as children compared to 60% among rural residents (1.43 (0.37-5.56)). The mean (IQR) AECT score was 14.0 (8.5-15.5) in urban patients and 13.0 (10.0-14.0) in rural patients (Poisson β -0.001 (-0.23-0.23). These data indicate that rural patients received similar high-quality care. We attribute these findings to the centralized care model employed in which HAE patients in the region are seen at a single comprehensive care clinic. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series.
- Author
-
Hoarau, Cyrille, Maleki, Alireza, Bouillet, Laurence, and Boccon-Gibod, Isabelle
- Subjects
- *
ANGIONEUROTIC edema , *PATIENT compliance , *ANDROGENS , *PATIENT preferences , *PREVENTIVE medicine - Abstract
Background: Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting. Results: Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan. Conclusions: Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Epidemiology, economic, and humanistic burden of hereditary angioedema: a systematic review.
- Author
-
Guan, Xin, Sheng, Yanan, Liu, Shuang, He, Miao, Chen, Tianxiang, and Zhi, Yuxiang
- Subjects
- *
MEDICAL personnel , *ANGIONEUROTIC edema , *TREATMENT delay (Medicine) , *CHINESE literature , *DIRECT costing , *EPIDEMIOLOGY - Abstract
Background: This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods: A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results: In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion: This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. The Burden of Hereditary Angioedema in a Large Family in Brazil.
- Author
-
Gehlen, Carolina Teló, Mazzeu, Juliana Forte, Veronez, Camila Lopes, Mendes, Agatha Ribeiro, Bertoli, Andrezza Fabrízia, Grumach, Anete Sevciovic, Pesquero, João Bosco, and da Silva, Jane
- Subjects
- *
ANGIONEUROTIC edema , *OLDER patients , *SOCIAL history , *SOCIAL impact , *SMALL cities , *URTICARIA - Abstract
Hereditary angioedema (HAE) is a rare genetic disease characterized by submucosal and subcutaneous edema with high morbidity and possibility of mortality. This study presents the sociodemographic characteristics of a large Brazilian family with HAE.Introduction: Descriptive cross-sectional study with patients from two family branches coming from the same city and HAE diagnosis was carried out. Clinical, laboratory, and treatment data of patients have been collected. Genetic testing was performed on some individuals. Correlation tests and comparisons between variables were applied using IBM SPSS Statistics® 2.0 program.Methods: We provide a detailed characterization of two families affected by HAE due to C1-INH deficiency, residing in a small town in southern Brazil. These families harbor an identified mutation in theResults: SERPING1 gene (c.1104del, p.Asp369Thrfs Ter2). The mean age at HAE diagnosis was 16.7 (±14.0) years, with the mean onset of symptoms at 6.0 (±6.1) years of age. A correlation was observed between patients’ current age and age at HAE diagnosis, with older patients being diagnosed later than younger individuals (p < 0.0001). On average, there were 16.8 emergency visits in the past year (±24.8), and 53.5% of patients reported at least one lifetime hospitalization. Notably, treatment modalities often diverged from consensus recommendations regarding optimal prophylaxis and management of HAE attacks. This study describes one of the largest known families with HAE in Brazil and highlights the significant impact of unfavorable social conditions on disease control. [ABSTRACT FROM AUTHOR]Conclusions: - Published
- 2024
- Full Text
- View/download PDF
32. Prophylaxis in hereditary angioedema: a United Kingdom Delphi consensus.
- Author
-
Yong, Patrick F K, Annals, Rachel, Diwakar, Lavanya, Elkhalifa, Shuayb, Gompels, Mark, Jain, Rashmi, Karim, Mohammed Yousuf, Khan, Sujoy, Metcalfe, Angela, Noorani, Sadia, Steele, Cathal, Kiani-Alikhan, Sorena, and Garcez, Tomaz
- Subjects
- *
DELPHI method , *PATIENT monitoring , *ANGIONEUROTIC edema , *PREVENTIVE medicine , *MEDICAL personnel - Abstract
Hereditary angioedema (HAE) is a rare inherited disorder causing recurrent episodes of swelling that can be potentially life threatening. Treatment of HAE can be divided into on-demand treatment for swelling, and prophylaxis. The last UK consensus on HAE was in 2014 and since then, new medications for prophylaxis have been developed, with more drugs in the pipeline. International guidelines currently recommend the use of long-term prophylaxis (LTP) as the only way of achieving disease control and normalizing patient lives. Modern prophylactic medications are available in the UK, although access is restricted primarily by HAE attack frequency. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding LTP as well as other aspects of HAE management. There was consensus that UK access criteria for modern LTP agents based on numerical frequency of attacks alone are too simplistic and potentially disadvantage a cohort of patients who may benefit from LTP. Additionally, there was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, and that the use of patient-reported outcome measures has the potential to improve patient care. Psychological health is an area in which patients may benefit, and recognition of this is important for future research and development. To establish an updated view of UK clinicians and patients, a Delphi process was used to develop statements regarding long-term prophylaxis and other aspects of hereditary angioedema management. UK access criteria for modern LTP agents based on numerical frequency of attacks alone were thought to be too simplistic, and potentially disadvantage a cohort of patients who may benefit from LTP. There was agreement that patients should be seen in expert centres, remote monitoring of patients is popular post-pandemic, patient-reported outcome measures has the potential to improve patient care, and psychological support may benefit patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Systemic inflammation biomarkers during angioedema attacks in hereditary angioedema.
- Author
-
Gil-Serrano, Johana, Horrillo, Moisés Labrador, Galvan-Blasco, Paula, Sala-Cunill, Anna, Bigas, Patricia, González, Javier Pereira, Luengo, Olga, Cardona, Victoria, and Guilarte, Mar
- Subjects
ACUTE phase proteins ,ANGIONEUROTIC edema ,BLOOD sedimentation ,LEUCOCYTES ,INFLAMMATORY mediators ,URTICARIA - Abstract
Background: Hereditary angioedema (HAE) is a rare disease characterized by localized and self-limited angioedema (AE) attacks. A local increase of bradykinin (BK) mediates AE attacks in HAE, however the role of inflammation in HAE has been poorly explored We aim to analyze the role of inflammatory mediators in HAE patients during AE attacks. Methods: Patients with a confirmed HAE diagnosis due to C1 inhibitor deficiency (HAE-C1INH) or patients F12 gene mutations (HAE-FXII) attending to our outpatient clinic between November-2019 and May-2022 were included. Demographic and clinical characteristics were analyzed. Blood samples were collected both during symptom-free periods (baseline) and during HAE attacks, and acute phase reactants (APR), such as serum amyloid A (SAA), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), D-Dimer and white blood cells were measured. Results: Seventy-eight patients were enrolled in the study, with a predominant representation of women (76%, n=59), and a mean age of 47.8 years (range 6-88). Among them, 67% (n=52) of patients had HAE-C1INH (46 classified as type 1 and 6 as type 2) while 33% (n=26) had HAE-FXII. During attack-free periods, the majority of patients exhibited normal levels of SAA, ESR, D-dimer, ACE and WCC. However, in a subset of patients (16% for SAA, 18% for ESR, and 14.5% for Ddimer), elevations were noted at baseline. Importantly, during HAE attacks, significant increases were observed in SAA in 88% of patients (p< 0.0001 vs. baseline), in ESR in 65% (p= 0.003 vs. baseline) and D-dimer in 71% (p=0.001 vs. baseline) of the patients. A comparison between baseline and acute attack levels in 17 patients revealed significant differences in SAA AA (p<0. 0001), ESR (p<0.0001) and D-dimer (p= 0.004). No significant differences were observed in CRP (p=0.7), ACE (p=0.67) and WCC (p=0.54). These findings remained consistent regardless of HAE type, disease activity or location of angioedema. Conclusion: The systemic increase in APR observed during HAE attacks suggests that inflammation extends beyond the localized edematous area. This finding underscores the potential involvement of inflammatory pathways in HAE and highlights the need for further investigation into their role in the pathophysiology of HAE. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. Uncovering a novel SERPING1 pathogenic variant: insights into the aggregation of C1-INH in hereditary angioedema
- Author
-
Lingxi Jiang, Chao Dai, Suyang Duan, Tingting Wang, Chunbao Xie, Luhan Zhang, Zimeng Ye, Xiumei Ma, and Yi Shi
- Subjects
Apoptosis ,Ca2+ overload ,C1-INH ,Hereditary angioedema ,SERPING1 pathogenic variant ,Medicine - Abstract
Abstract Background Hereditary angioedema (HAE) is a rare autosomal dominant genetic disease characterized by recurrent edema and a potentially fatal risk. Despite its severity, there is a notable lack of effective methods for predicting and preventing HAE attacks. This study aims to thoroughly investigate the underlying pathological mechanisms of HAE and identify potential biomarkers that could aid in its prediction and prevention. Results In our investigation, we have discovered a novel pathogenic variant of the SERPING1 gene, specifically c.708T > G, in a Han family affected by HAE. Our observations indicate that this variant leads to an increase in the accumulation of C1-INH within the endoplasmic reticulum (ER), resulting in the upregulation of GRP75 protein expression. This cascade of events resulted in Ca2+ overload, disruption of mitochondrial structure and function, and eventually triggered apoptosis. Using siRNA to knock down GRP75 mitigates cellular calcium overload and mitochondrial damage induced by the SERPING1 mutation. Conclusion Based on our findings, we propose that the detection of intracellular Ca2+ concentration could serve as a valuable biomarker for predicting acute attacks of HAE in patients. This discovery holds significant implications for the development of more targeted and effective strategies in the management of HAE.
- Published
- 2024
- Full Text
- View/download PDF
35. A human centred innovative approach based on persona in hereditary angioedema
- Author
-
Francesca Perego, Lorenza Chiara Zingale, Azzurra Cesoni Marcelli, Luca Ranucci, Lorenzo Rimoldi, Nurgul Nsanbayeva, Maria Rosaria Natale, Laura Adelaide Dalla Vecchia, and Alessandra Gorini
- Subjects
Hereditary angioedema ,Personas ,Human center design ,Unmet needs ,Prevention ,Rehabilitation ,Medicine - Abstract
Abstract Background Hereditary Angioedema (HAE) due to C1-inhibitor deficiency (C1INH) is a rare condition, clinically characterised by recurrent swelling. The unpredictability of attacks affects the patients’ quality of life (QoL). HAE patients and their families have vast unmet physical, psychological, and social needs. A human-centred design (HCD) approach to describing the needs of different user types is to utilise personas, a data-driven narrative tool for communicating user archetypes that capture the individuals’ attitudes, goals, and behaviours. The aim of this study was to create and analyse personas based on HAE patients’ and their caregivers’ interviews. Semi-structured interviews were conducted through anthropological conversations with patients, patient-caregivers (double role of patient and caregiver), and non-affected caregivers. Qualitative and quantitative insights from analyses formed the basis to create personas. Results We enrolled 17 subjects: 15 patients (6 of them were patient-caregivers) and 2 non-affected caregivers. The mean age of participants was 50.3 ± 14.4 years. Eight patients were on treatment with prophylactic therapy. The mean percentage score of Angioedema Quality of Life (AE-QoL) for HAE patients was 19.8 ± 12.0. Six personas were identified describing the participants’ personal history, disease management, and needs: four personas referred to patients, one to patient-caregivers, and one non-affected caregiver personas were identified. Across patient personas, the most expressed needs were psychological support and better awareness amongst healthcare professionals. Caregivers, on their side, desired better information about the disease, including the latest therapies, and higher awareness within the community. Conclusion A Human Centred Innovative Approach Based on Persona extends beyond the physical symptoms to encompass the psychological and social aspects of the individual's well-being also including the family in the evaluation.
- Published
- 2024
- Full Text
- View/download PDF
36. Androgen transition and management of hereditary angioedema long-term prophylaxis in real life: a single-center case series
- Author
-
Cyrille Hoarau, Alireza Maleki, Laurence Bouillet, and Isabelle Boccon-Gibod
- Subjects
Attenuated androgens ,Berotralstat ,Lanadelumab ,C1 inhibitor ,Hereditary angioedema ,Medicine - Abstract
Abstract Background Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that manifests clinically as recurrent episodes of swelling affecting multiple anatomical locations. Long-term prophylaxis (LTP) aims to control the disease by preventing HAE attacks. Previously, treatments such as attenuated androgens have been used for LTP, but they have an unfavorable adverse effect profile. Today, these limitations may be overcome by patients transitioning to newer, targeted therapies including oral berotralstat and subcutaneous lanadelumab. This case series reports the transition process between different prophylactic therapies in a family with HAE in a real-world setting. Results Four adult patient cases from the same family who underwent transitions in HAE prophylaxis are presented. Three were female and one male. Two patients who transitioned to berotralstat were initially prescribed attenuated androgens. Two patients were not taking LTP at the time of initiating targeted treatment but had previously been prescribed tranexamic acid. The length of transition varied between the patients, with the longest time taken to stabilize on new therapy being 26 months. All patients received regular follow-up in person or by telephone and all four required an adjustment from their initial treatment plan. Conclusions Transitioning between LTP in HAE may help improve control of attacks, avoid unwanted adverse effects, or better cater to individual patient preferences. Newer targeted therapies have been shown to be effective and should be discussed with patients. Shared decision-making is a tool that can aid these discussions. The transition journey between LTP therapies in HAE may not be straightforward and is specific to each patient. Physicians should consider complicating factors such as patient anxieties around changing treatment, adverse effects, preferred routes of administration, and speed of transition. Following patients closely during the transition period helps identify any issues, including difficulties with treatment adherence, and may allow the transition plan to be adapted when necessary.
- Published
- 2024
- Full Text
- View/download PDF
37. Epidemiology, economic, and humanistic burden of hereditary angioedema: a systematic review
- Author
-
Xin Guan, Yanan Sheng, Shuang Liu, Miao He, Tianxiang Chen, and Yuxiang Zhi
- Subjects
Hereditary angioedema ,Autosomal disorder ,Economic cost ,Clinical burden ,Quality of life ,Medicine - Abstract
Abstract Background This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema. Methods A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377). Results In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children. Conclusion This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society.
- Published
- 2024
- Full Text
- View/download PDF
38. A clinical evaluation of patients with known mutations (plasminogen and factor XII) with a focus on prophylactic treatment.
- Author
-
Lochbaum, Robin, Trainotti, Susanne, Hoffmann, Thomas K., Greve, Jens, and Hahn, Janina
- Subjects
- *
PLASMINOGEN , *HEALTH facilities , *GENETIC disorders , *ANGIONEUROTIC edema , *TREATMENT effectiveness - Abstract
Background: Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease. The symptoms can resemble other forms of hereditary angioedema (HAE), but the specific laboratory values are inconspicuous. The knowledge about treatment strategies in HAE-nC1-INH remains insufficient; most of the drugs are only licensed and approved for other types of HAE. Methods: An analysis of all patients with HAE-nC1-INH was carried out in a certified angioedema treatment center in southern Germany. Only patients with a confirmed HAE-nC1-INH mutation were included. The impact of disease was monitored with validated questionnaires. Results: Eighteen patients were included: two families with a factor XII mutation and seven families with a plasminogen mutation. All individuals received icatibant for on-demand therapy—efficient treatment response was reported. Three patients were severely affected, and prophylaxis was initiated with lanadelumab. According to the questionnaires, the clinical course and symptoms improved significantly under this prophylactic regime. Conclusion: This is one of the first descriptions of the clinical outcomes as a response to prophylactic treatment with lanadelumab in HAE-nC1-INH patients with a known mutation. The therapeutic management of HAE-1 and HAE-2 should also be the basis of HAE-nC1-INH, including prophylaxis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Maxillary sinus augmentation in a patient with hereditary angioedema with normal C1 inhibitor and familial Mediterranean fever.
- Author
-
Watanabe, Takuma, Mano, Nodoka, and Yamashita, Kouhei
- Abstract
Hereditary angioedema (HAE) with normal C1 inhibitor (C1-INH) (HAE-nC1-INH) is a rare disease that presents with laryngeal edema due to oral surgical procedures. Familial Mediterranean fever (FMF) is a disorder commonly characterized by an autosomal recessive inflammatory process, and manifests in the oral cavity and facial structures. A 50-year-old woman with HAE-nC1-INH and FMF was referred to our department for bone augmentation in the right maxillary molar region. We performed lateral window sinus augmentation under the backup support of an anesthesiologist. A hematologist used intravenous Berinert® and oral Orladeyo® to prevent perioperative angioedema attacks. The postoperative course was uneventful. Regarding surgical intervention in patients with HAE, interdepartmental cooperation is crucial to prevent angioedema attacks and prepare for life-threatening complications. Oral hygiene and occlusion should be considered in the dental implant treatment of patients with FMF. Every oral and maxillofacial surgeon and dental practitioner should familiarize themselves with HAE and FMF. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Hereditary Angioedema: The Clinical Picture of Excessive Contact Activation.
- Author
-
Petersen, Remy S., Fijen, Lauré M., Levi, Marcel, and Cohn, Danny M.
- Abstract
Hereditary angioedema is a rare, genetic disorder characterized by painful, debilitating and potentially life-threatening angioedema attacks in subcutaneous and submucosal tissue. While usually unpredictable, attacks can be provoked by a variety of triggers including physical injury and certain medication and are often preceded by prodromal symptoms. Hereditary angioedema has a profound influence on the patients' lives. The fundamental cause of hereditary angioedema in almost all patients is a mutation in the SERPING1 gene leading to a deficiency in C1-inhibitor. Subsequently, the contact activation cascade and kallikrein-kinin pathway are insufficiently inhibited, resulting in excessive bradykinin production triggering vascular leakage. While C1-inhibitor is an important regulator of the intrinsic coagulation pathway, fibrinolytic system and complement cascade, patients do not have an increased risk of coagulopathy, autoimmune conditions or immunodeficiency disorders. Hereditary angioedema is diagnosed based on C1-inhibitor level and function. Genetic analysis is only required in rare cases where hereditary angioedema with normal C1-inhibitor is found. In recent years, new, highly specific therapies have greatly improved disease control and angioedema-related quality of life. This article reviews the clinical picture of hereditary angioedema, the underlying pathophysiology, diagnostic process and currently available as well as investigational therapeutic options. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Assessing the control of the disease on current treatments available in Romania for hereditary angioedema patients
- Author
-
Bara Noemi Anna, Nadasan Iris, Nadasan Valentin, and Deleanu Diana
- Subjects
angioedema ,hereditary angioedema ,quality of life ,on-demand ,long-term prophylaxis ,Medicine - Abstract
Background: Acute treatment must be permanently accessible for every patient diagnosed with hereditary angioedema (HAE). In many cases this type of therapy does not provide/offer sufficient control of the disease, so long-term prophylaxis (LTP) is recommended. In the case of regular and prolonged/extended administration of drugs, the route of administration is essential. The aim of the investigation was to assess the control of HAE among patients in Romania receiving the available medications, while also examining potential correlations within the outcomes.
- Published
- 2024
- Full Text
- View/download PDF
42. Hereditary angioedema in Spain: medical care and patient journey
- Author
-
Teresa Caballero, Carmen Alonso, María Luisa Baeza, Krasimira Baynova, José Cabeza, Isabel Cortés, Danilo Escobar Oblitas, Mar Guilarte, Alejandro Joral, Jesús Jurado Palomo, María Ángeles Lara Jiménez, Ana Martínez Virto, Laura Medrano, Emilio Monte Boquet, Montserrat Navarro, Diego Pérez, María José Plá Martí, Sara L. Smith Foltz, Coral Suero, and Carolina Zamora
- Subjects
Hereditary angioedema ,Patient journey ,Recommendations ,Acute attacks ,Short-term prophylaxis ,Long-term prophylaxis ,Medicine - Abstract
Abstract Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain. Methods A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model. Results Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged. Conclusions The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management.
- Published
- 2024
- Full Text
- View/download PDF
43. Sebetralstat: A Rapidly Acting Oral Plasma Kallikrein Inhibitor for the On-Demand Treatment of Hereditary Angioedema
- Author
-
Edward P. Feener, Rebecca L. Davie, Nivetha Murugesan, Stephen J. Pethen, Sally L. Hampton, Michael D. Smith, Paul K. Audhya, and Chris M. Yea
- Subjects
plasma kallikrein ,hereditary angioedema ,kallikrein kinin system ,bradykinin ,oral treatment ,plasma kallikrein inhibitor ,Pharmacy and materia medica ,RS1-441 ,Chemistry ,QD1-999 - Abstract
Sebetralstat is a novel, potent, and selective oral plasma kallikrein inhibitor drug candidate in clinical development for the on-demand treatment of hereditary angioedema (HAE). Upon binding, sebetralstat induces a conformational change in the active site of plasma kallikrein, which contributes to its high potency (Ki 3 nM) and selectivity (>1500 fold) against other serine proteases. Its physiochemical properties promote both rapid dissolution in the stomach and rapid absorption in the upper intestine that contribute to its fast and efficient absorption. A single oral administration of sebetralstat rapidly provides near-complete inhibition of plasma kallikrein and blockade of high-molecular-weight kininogen cleavage as early as 15 min, which drives its clinical efficacy. In a phase 2 clinical trial, sebetralstat significantly reduced the time to beginning of symptom relief (p < 0.0001) with median times of 1.6 h (95% CI: 1.5–3.0) with sebetralstat versus 9.0 h (4.0–17.2) with placebo. KONFIDENT (NCT05259917) is a phase 3 clinical trial assessing the on-demand use of sebetralstat for HAE. If successful, this trial could support the approval of sebetralstat as the first noninvasive, on-demand treatment option to rapidly halt HAE attacks and provide fast symptom relief.
- Published
- 2024
- Full Text
- View/download PDF
44. Clinical and laboratory spectrum of hereditary angioedema in a group of Egyptian children: a cross sectional study
- Author
-
Mohamed Almalky, Reham M. El Shabrawy, Najeeb Ali Mohammed Gheetah, Hossam Moustafa Elkady, Naglaa S. Osman, Walaa Shoman, and Eman Gamal Baz
- Subjects
Hereditary angioedema ,Children ,Clinical presentations ,Laboratory presentations ,Egypt ,Pediatrics ,RJ1-570 - Abstract
Abstract Background Hereditary angioedema (HAE) is a hereditary illness represented by repeated bouts of submucosal or subcutaneous edema. Types of HAE includes; HAE with deficient C1-inhibitor (type 1), HAE with dysfunctional C1-inhibitor (type 2), and HAE with normal C1-inhibitor. Data on the epidemiology of HAE in Egypt are limited. Therefore, we aimed to characterize HAE in Egyptian children, identify the morbidity, and clarify HAE's different clinical and laboratory presentations. Methods In this cross-sectional study, we enrolled pediatric patients diagnosed with HAE according to the international hereditary angioedema WAO/EAACI guidelines. We gathered laboratory data on patients' mean serum C1 esterase inhibitor (C1-INH) level and activity, C4, and IgE levels. Results We included 18 HAE patients (14 females and 4 males). They were between the ages of 6 and 18 years. The mean age upon confirmation of diagnosis was 8.4 ± 2.4 years. The mean time required to correctly diagnose HAE was 3.2 ± 1.8 years. We detected type I in 15 cases and type II in three cases. Eleven patients had a family member with HAE. In terms of previous misdiagnoses, 50% of patients were diagnosed with allergic angioedema. The median annual frequency of episodes was 17. The mean HAE attack time was 2.9 ± 1.5 days. Edema was most typically found in the face and abdomen. Trauma was the main triggering factor. We detected a significant direct relationship between severity of attack and C1-INH activity level. Conclusions This research adds a considerable clinical information about children with HAE. According to current results, there is a considerable underdiagnosis of HAE in Egypt. The detection and management of HAE can be improved by screening the relatives of HAE patients.
- Published
- 2024
- Full Text
- View/download PDF
45. Sebetralstat: A Rapidly Acting Oral Plasma Kallikrein Inhibitor for the On-Demand Treatment of Hereditary Angioedema.
- Author
-
Feener, Edward P., Davie, Rebecca L., Murugesan, Nivetha, Pethen, Stephen J., Hampton, Sally L., Smith, Michael D., Audhya, Paul K., and Yea, Chris M.
- Subjects
- *
KALLIKREIN , *ANGIONEUROTIC edema , *ORAL drug administration , *CLINICAL trials , *SERINE proteinases , *URTICARIA - Abstract
Sebetralstat is a novel, potent, and selective oral plasma kallikrein inhibitor drug candidate in clinical development for the on-demand treatment of hereditary angioedema (HAE). Upon binding, sebetralstat induces a conformational change in the active site of plasma kallikrein, which contributes to its high potency (Ki 3 nM) and selectivity (>1500 fold) against other serine proteases. Its physiochemical properties promote both rapid dissolution in the stomach and rapid absorption in the upper intestine that contribute to its fast and efficient absorption. A single oral administration of sebetralstat rapidly provides near-complete inhibition of plasma kallikrein and blockade of high-molecular-weight kininogen cleavage as early as 15 min, which drives its clinical efficacy. In a phase 2 clinical trial, sebetralstat significantly reduced the time to beginning of symptom relief (p < 0.0001) with median times of 1.6 h (95% CI: 1.5–3.0) with sebetralstat versus 9.0 h (4.0–17.2) with placebo. KONFIDENT (NCT05259917) is a phase 3 clinical trial assessing the on-demand use of sebetralstat for HAE. If successful, this trial could support the approval of sebetralstat as the first noninvasive, on-demand treatment option to rapidly halt HAE attacks and provide fast symptom relief. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Unveiling therapeutic frontiers: DON/DRP-104 as innovative Plasma kallikrein inhibitors against carcinoma-associated hereditary angioedema shocks - a comprehensive molecular dynamics exploration.
- Author
-
Oduro-Kwateng, Ernest and Soliman, Mahmoud E. S.
- Abstract
Human plasma kallikrein (PKa) is a member of the serine protease family and serves as a key mediator of the kallikrein-kinin system (KKS), which is known for its regulatory roles in inflammation, vasodilation, blood pressure, and coagulation. Genetic dysregulation of KKS leads to Hereditary Angioedema (HAE), which is characterized by spontaneous, painful swelling in various body regions. Importantly, HAE frequently coexists with various cancers. Despite substantial efforts towards the development of PKa inhibitors for HAE, there remains a need for bifunctional agents addressing both anti-cancer and anti-HAE aspects, especially against carcinoma-associated comorbid HAE conditions. Consequently, we investigated the therapeutic potential of the anti-glutamine prodrug, isopropyl(S)-2-((S)-2-acetamido-3-(1H-indol-3-yl)-propanamido)-6-diazo-5-oxo-hexanoate (DRP-104), and its active form, 6-Diazo-5-oxo-l-norleucine (DON), recognized for their anti-cancer properties, as novel PKa inhibitors. Utilizing structure-based in silico methods, we conducted a comparative analysis with berotralstat, a clinically approved HAE prophylactic, and sebetralstat, an investigational HAE therapeutic agent, in Phase 3 clinical trials. Inhibiting PKa with DON resulted in relatively heightened structural stability, rigidity, restricted protein folding, and solvent-accessible loop exposure, contributing to increased intra-atomic hydrogen bond formation. Conversely, PKa inhibition with DRP-104 induced restricted residue flexibility and significantly disrupted the critical SER195-HIS57 arrangement in the catalytic triad. Both DON and DRP-104, along with the reference drugs, induced strong cooperative intra-residue motion and bidirectional displacement in the PKa architecture. The results revealed favorable binding kinetics of DON/DRP-104, showing thermodynamic profiles that were either superior or comparable to those of the reference drugs. These findings support their consideration for clinical investigations into the management of carcinoma-associated HAE. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Effect of lanadelumab on attack frequency and QoL in Japanese patients with hereditary angioedema: Report of five cases.
- Author
-
Hioki, Chika, Oda, Yoshiko, Moriwaki, Shinichi, and Fukunaga, Atsushi
- Abstract
Lanadelumab, a recombinant human anti‐kallikrein monoclonal antibody, is recommended as the first‐line option for long‐term prophylaxis (LTP) in hereditary angioedema (HAE). However, the efficacy of lanadelumab and its effects on the quality of life (QoL) in Japanese HAE patients using real‐world data have not been reported. Herein, we report the outcomes of five HAE patients who were treated with lanadelumab at two Japanese institutions. We retrospectively collected data on attack frequency and on‐demand treatment frequency using an angioedema quality of life (AE‐QoL) questionnaire. Our data corresponded to five Japanese HAE patients who started lanadelumab treatment: four with HAE due to C1‐inhibitor deficiency (HAE‐1) and one with HAE with a normal C1‐inhibitor (HAE‐nC1‐INH). Two HAE‐1 patients showed a reduction in both attacks and number of on‐demand treatments. The other HAE‐1 patients had an increase in the number of on‐demand treatments, although there was no apparent reduction in attacks. The HAE‐nC1‐INH patient showed a slight increase in both attacks and number of on‐demand treatments. Only one HAE‐1 patient discontinued treatment after 1 month owing to side effects, including dizziness and headache. All four who continued treatment showed improved AE‐QoL total and domain scores. Therefore, in this study, using real‐world data, we demonstrated that lanadelumab reduced attack frequency and improved QoL in Japanese HAE patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. Mast cell degranulation and bradykinin-induced angioedema - searching for the missing link.
- Author
-
Porebski, Grzegorz, Dziadowiec, Alicja, Rybka, Hubert, Kitel, Radoslaw, and Kwitniewski, Mateusz
- Subjects
MAST cells ,ANGIONEUROTIC edema ,MUCOUS membranes ,BRADYKININ ,POLYANIONS ,URTICARIA ,MAST cell disease - Abstract
Initiation of the bradykinin generation cascade is responsible for the occurrence of attacks in some types of angioedema without wheals. Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1-INH) is one such clinical entity. In this paper, we explore the existing evidence that mast cells (MCs) degranulation may contribute to the activation of the kallikrein-kinin system cascade, followed by bradykinin formation and angioedema. We present the multidirectional effects of MC-derived heparin and other polyanions on the major components of the kinin-kallikrein system, particularly on the factor XII activation. Although, bradykinin- and histamine-mediated symptoms are distinct clinical phenomena, they share some common features, such as some similar triggers and a predilection to occur at sites where mast cells reside, namely the skin and mucous membranes. In addition, recent observations indicate a high incidence of hypersensitivity reactions associated with MC degranulation in the HAE-C1-INH patient population. However, not all of these can be explained by IgE-dependent mechanisms. Mast cell-related G protein-coupled receptor-X2 (MRGPRX2), which has recently attracted scientific interest, may be involved in the activation of MCs through a different pathway. Therefore, we reviewed MRGPRX2 ligands that HAE-C1-INH patients may be exposed to in their daily lives and that may affect MCs degranulation. We also discussed the known inter-and intra-individual variability in the course of HAE-C1-INH in relation to factors responsible for possible variability in the strength of the response to MRGPRX2 receptor stimulation. The above issues raise several questions for future research. It is not known to what extent a prophylactic or therapeutic intervention targeting the pathways of one mechanism (mast cell degranulation) may affect the other (bradykinin production), or whether the number of mast cells at a specific body site and their reactivity to triggers such as pressure, allergens or MRGPRX2 agonists may influence the occurrence of HAE-C1-INH attacks at that site. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. The real life experience goes on: update after 4 years on the first cohort treated with lanadelumab at our center.
- Author
-
Buttgereit, Thomas, Ayala, Carolina Vera, Aykanat, Seda, Weller, Karsten, Gutsche, Annika, Maurer, Marcus, and Magerl, Markus
- Subjects
PATIENT satisfaction ,REPORTING of diseases ,ANGIONEUROTIC edema ,QUALITY of life ,PREVENTIVE medicine - Abstract
Introduction: Lanadelumab 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). Objectives: To provide 4-year follow-up data for our first 34 patients treating with lanadelumab. Methods: Patients were assessed for their current injection interval, attacks, treatment satisfaction, disease control (AECT), quality of life impairment (AEQoL), events that can induce attacks, and the use of STP since the start of their treatment with lanadelumab. Results: Of 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. Conclusions: Our 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. Hereditary angioedema in Spain: medical care and patient journey.
- Author
-
Caballero, Teresa, Alonso, Carmen, Luisa Baeza, María, Baynova, Krasimira, Cabeza, José, Cortés, Isabel, Escobar Oblitas, Danilo, Guilarte, Mar, Joral, Alejandro, Jurado Palomo, Jesús, Lara Jiménez, María Ángeles, Martínez Virto, Ana, Medrano, Laura, Monte Boquet, Emilio, Navarro, Montserrat, Pérez, Diego, Plá Martí, María José, Smith Foltz, Sara L., Suero, Coral, and Zamora, Carolina
- Abstract
Background Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a genetic rare disease characterized by recurrent, transient and unpredictable episodes of cold, non-pruriginous oedema without associated urticaria. The characteristics of the disease have a considerable impact on the quality of life of patients. The aim of this study was to increase understanding of the patient journey of HAE in Spain. Methods A multidisciplinary committee of 16 HAE experts (allergy, immunology, emergency department, hospital pharmacy and nursing) and 3 representatives of the Spanish Hereditary Angioedema Patient Association (AEDAF) who were patients or caregivers participated in the study. A review of the publications on HAE treatment was performed. Semi-structured interviews were performed to HAE experts, patients, or caregivers. Three meetings with the experts, patients and caregivers were held to share, discuss, and validate data obtained from literature and interviews and to build the model. Results Throughout the project, the patient journey has been drawn up, dividing it into the stages of pre-diagnosis, diagnosis and treatment/follow-up. Some areas for improvement have been identified. Firstly, there is a need to enhance awareness and training on HAE among healthcare professionals, with a particular emphasis on primary care and emergency department personnel. Secondly, efforts should be made to minimize patient referral times to allergy/immunology specialists, ensuring timely access to appropriate care. Thirdly, it is crucial to encourage the study of the relatives of diagnosed patients to early identify potential cases. Fourthly, equitable access to self-administered treatments should be ensured, facilitated by systems that enable medication delivery at home and proper education and training for patients. Equitable access to long-term prophylactic treatment should also be prioritized for all patients in need. To standardize HAE management, the development of consensus guidelines that reduce variability in clinical practice is essential. Lastly, promoting research studies to enhance knowledge of the disease and align its treatment with new developments in the healthcare field should be encouraged. Conclusions The knowledge of the patient journey in HAE allowed us to identify improvement areas with the final aim to optimize the disease management. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.