icatibant / Generic mfg. - LARVOL DELTA

Urgent diagnosis of hereditary angioedema in the ICU and ED: the critical role of rapid complement testing - a case report. (PubMed, Int J Emerg Med) - "This case highlights the importance of considering HAE in patients presenting with unexplained slowly-evolving angioedema without urticaria, when traditional histamine-directed therapies fail, especially when airway compromise is imminent. Awareness that C4 levels are universally low during HAE attacks, is key. C4 testing is widely available and prompt communication with biochemistry or immunology laboratories facilitates rapid turnaround. Urgent presumptive diagnosis facilitates appropriate emergency management and prompt referral for definitive diagnosis and management. Early identification and management of HAE can significantly reduce morbidity and mortality associated with this condition."

Journal • Allergy • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Immunology • Urticaria

Management of hereditary angioedema with normal C1Inh: a series of 163 French patients. (PubMed, Orphanet J Rare Dis) - "HAE patients with a normal C1inh have specific clinical features, including a later age at first attack than HAE patients with a normal C1inh, high sensitivity to estrogens of HAE-FXII and the location of the HAE-PLG on the tongue. The treatments used for HAE patients with C1Inh deficiency appear to be effective and safe. Low-dose progestin-only pills are good contraceptive options."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Targeting MRGPRX2: A Transformative Approach to Inflammatory Skin Conditions (ISDS 2025) - "Clinically, oral EVO756 suppressed icatibant-induced wheal formation in a phase 1 trial, confirming its ability to inhibit MRGPRX2-mediated responses in humans. These findings establish MRGPRX2 as a master regulator of mast cell and sensory neuron activation, driving neurogenic inflammation in CSU, AD, and beyond. EVO756 offers a potential groundbreaking therapeutic strategy, delivering multipronged benefits by targeting key pathogenic pathways across inflammatory skin diseases and other chronic inflammatory conditions."

Atopic Dermatitis • Chronic Spontaneous Urticaria • Dermatitis • Dermatology • Immunology • Inflammation • Urticaria • IL33

Implementation of genetic diagnosis and personalized management of hereditary angioedema in a Chinese regional center: a community case study of three families. (PubMed, Front Allergy) - "The program included standardized clinical assessment and real-time biochemical screening (C4, C1 inhibitor concentration/function), targeted SERPING1 sequencing and variant classification American College of Medical Genetics and Genomics (ACMG), family cascade screening and genetic counseling, stratified personalized treatment (on-demand icatibant and lanadelumab prophylaxis), electronic follow-up Angioedema Control Test (AECT)/Angioedema Quality of Life Questionnaire (AE-QoL), and quality management [Standard Operating Procedures (SOPs) and provincial External Quality Assessment (EQA) planning)]. Key facilitating factors included cascade screening and genetic counseling, standardized testing pathways and variant classification, flexible prophylactic strategies adapted to economic conditions, and electronic quality and outcome monitoring. This program has expanded the domestic SERPING1 variant spectrum and provides preliminary insights and references for the future..."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

The Involvement of the Peptidergic Systems in Breast Cancer Development. (PubMed, Cancers (Basel)) - "Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1-7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin)...Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9-39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review...Taken together, the available data highlight the enormous promise..."

Journal • Review • Breast Cancer • Oncology • Solid Tumor • GRP-10

Association between Toll-like receptor 9 signaling defect and developing post-infectious irritable bowel syndrome. (PubMed, Front Immunol) - "Furthermore, administration of BDKRB1 antagonist R715 and BDKRB2 antagonist HOE 140 significantly suppressed visceral hyperalgesia. TLR9 deficiency leads to bradykinin receptor upregulation in the colonic epithelium following infectious colitis, contributing to the development of PI-IBS. Inhibition of these receptors alleviated visceral pain, indicating that bradykinin receptor antagonists may offer a novel therapeutic strategy for PI-IBS."

IO biomarker • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Inflammation • Mucositis • Pain • BDKRB2 • TLR2 • TLR9

A Survey of Icatibant in Pediatric Participants With Hereditary Angioedema (clinicaltrials.gov) - P=N/A | N=32 | Completed | Sponsor: Takeda | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema • Pediatrics

Recurrent Airway Swelling in a Patient With Lymphoproliferative Disorder: A Diagnostic Challenge Between Anaphylaxis and Acquired Angioedema. (PubMed, Cureus) - "Considering refractory anaphylaxis, she received intravenous dexamethasone, an adrenaline nebulizer, and an adrenaline infusion. Given her history of CD5-negative low-grade B-cell lymphoproliferative disorder, a diagnosis of acquired angioedema was made following multidisciplinary review, and treatment with icatibant was initiated. This case highlights the importance of considering bradykinin-mediated angioedema in patients with recurrent "refractory anaphylaxis." The absence of urticaria, normal tryptase, and low complement levels should prompt evaluation for C1-INH deficiency, allowing timely, targeted management and improved outcomes."

Journal • Cardiovascular • Dermatology • Gastrointestinal Disorder • Hereditary Angioedema • Immunology • Pruritus • Urticaria • CD5

Swelling from the Inside Out: Atypical AKI Triggered by Gastrointestinal Hereditary Angioedema Flare (KIDNEY WEEK 2025) - "He had missed his scheduled Takhzyro prophylaxis for over five weeks...Immunosuppressive agents (Cellcept, Acthar) were held...Bradykinin-mediated GI angioedema should be considered in the differential of unexplained AKI in patients with known or suspected HAE. Prompt treatment with Firazyr can reverse systemic symptoms and facilitate renal recovery, underscoring the importance of multidisciplinary collaboration in complex cases."

Acute Kidney Injury • Cardiovascular • Chronic Kidney Disease • Complement-mediated Rare Disorders • Endocrine Disorders • Focal Segmental Glomerulosclerosis • Gastrointestinal Disorder • Glomerulonephritis • Hereditary Angioedema • Immunology • Inflammation • Nephrology • Rare Diseases • Renal Disease

Current Use of Hereditary Angioedema (HAE) Treatments in Sweden: An Analysis of the National Prescribed Drug Register (ISPOR-EU 2025) - "Icatibant was the most dispensed concomitant treatment to LTP, followed by pdC1-INH. The observed prevalence aligns with prior estimates, though the incidence, when measured as number of new patients treated for HAE, is higher than what has been observed elsewhere. Despite restrictive reimbursement criteria, lanadelumab is the most prescribed LTP. The dispensing of on-demand/short-term treatment at least three times annually, indicates that a large share of patients potentially are not attack-free despite treatment with LTP."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Barely There But Existent: Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema. (PubMed, Cureus) - "On this occasion, she presented with upper airway swelling secondary to angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema, requiring endotracheal intubation. Initial management in the A&E department, under differential consideration for anaphylaxis and Ludwig's angina, included oxygen via a non-rebreather mask (NRM), intramuscular adrenaline, intravenous dexamethasone, nebulization with Pulmicort, and antibiotic coverage with ceftriaxone and metronidazole...ACEI-induced angioedema is a rare but potentially life-threatening adverse effect of ACEIs, which are widely prescribed for hypertension, heart failure, and chronic kidney disease. A thorough medication history is essential for the timely recognition and management of this condition."

Journal • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Coronary Artery Disease • Heart Failure • Hypertension • Infectious Disease • Nephrology • Obstructive Sleep Apnea • Renal Disease • Respiratory Diseases • Sleep Disorder

Bradykinin-Mediated Angioedema Complicating Hospitalization For Behcet's-like Disease (ACAAI 2025) - "Prodromal throat discomfort began >24 hours prior to peak swelling, preceded by menstruation, ACE-inhibitor use one week earlier, and infliximab initiation five days prior...After extubation, she had recurrent angioedema that responded well to icatibant...She was discharged with sebetralstat, an oral plasma kallikrein inhibitor, for rescue. This case underscores mechanism-guided therapy to angioedema, regardless of molecular diagnosis, especially when laboratory findings are pending or inconclusive."

Clinical • Cardiovascular • Dermatology • Immunology • Pruritus • Urticaria

Acquired Angioedema with C1 Esterase Inhibitor Deficiency Alerts to Possible Worsening Malignancy (ACAAI 2025) - "Prior to these episodes of angioedema, the patient’s lymphoma was presumed to be in remission on zanubrutinib...The patient acute angioedema responded to treatment with icatibant...Addition of Rituximab seemed to be helpful in managing underlying lymphoma. Future directions will involve possible weaning of the frequency of lanadelumab and/or Rituximab."

B Cell Lymphoma • Cardiovascular • Dermatology • Hematological Malignancies • Hereditary Angioedema • Immunology • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases • Splenic Marginal Zone Lymphoma • Urticaria

A Coagulation Connection in Idiopathic Angioedema (ACAAI 2025) - "Multiple therapies including antihistamines, steroids, IVIG, plasmapheresis, omalizumab, danazol, and icatibant were ineffective...Edoxaban was ineffective; warfarin re-initiation led to temporary improvement...Recurrence despite ongoing anticoagulation suggests a complex, multifactorial pathophysiology. This case supports further exploration of coagulation abnormalities in idiopathic angioedema."

Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Endocrine Disorders • Hereditary Angioedema • Immunology • Pruritus • Pulmonary Arterial Hypertension • Pulmonary Disease • Pulmonary Embolism • Respiratory Diseases • Urticaria

Berotralstat Is Effective In Early Onset HAE With Normal C1 Esterase Inhibitor (ACAAI 2025) - "Previously failed treatments included C1 esterase inhibitor, lanadelumab-flyo, progestin, and omalizumab, which were either ineffective or caused significant side effects. She required icatibant injections for acute attacks due to the severity of symptoms...In one case series that demonstrated the effectiveness of berotralstat in this condition, most patients had adult-onset presentations (average age of onset for these patients was 32 years), whereas only 2 out of the 15 patients had childhood-onset presentations (ages unreported). Our case demonstrates the effectiveness of berotralstat in early onset HAE-nC1-INH."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

Diagnostic Challenge of Late-Onset HAE with Normal C1 Esterase Levels and FXII c.-4T>C Variant (ACAAI 2025) - "She was treated with epinephrine, corticosteroids, antihistamines, and a single dose of icatibant. Discussion This expands the clinical spectrum of HAE-nC1-INH by demonstrating late-onset presentation in an elderly patient. While prior studies link the c.-4T>C polymorphism to increased severity with the p.Thr328Lys mutation, our case identifies the c.-4T>C variant in a suggestive clinical setting despite the absence of classical FXII mutations."

Complement-mediated Rare Disorders • Esophageal Adenocarcinoma • Esophageal Cancer • Hereditary Angioedema • Solid Tumor

Hereditary Angioedema with Normal C1 Esterase Inhibitor in a Male with PLG and SERPING1 Mutations (ACAAI 2025) - "Prednisone and montelukast offered only fleeting relief as attacks intensified. Icatibant swiftly halted flares, with symptoms clearing in days. Five months later, we began biweekly lanadelumab-flyo (300 mg q2wk)...Discussion This rare male case of HAE-nC1-INH with PLG and SERPING1 mutations underscores the urgency and necessity of repeated complement testing and targeted therapies to provide life-altering symptomatic management. Clinicians should maintain a high degree of suspicion and consider confirmation with genetic sequencing in cases of refractory angioedema in male patients."

Cardiovascular • Complement-mediated Rare Disorders • Fatigue • Hereditary Angioedema • Pulmonary Disease • ANGPT1

Of Swells and Cells: Two Birds One Inhibitor (ACAAI 2025) - "Due to severity and frequency of attacks, she was started on lanadelumab, responding well with only 4 mild breakthrough attacks requiring icatibant each year. Discussion Early reports of HAE-nC1 were described exclusively in female patients, supporting an association with estrogen. In the setting of our patient’s concomitant use of an aromatase inhibitor letrozole for estrogen receptor positive breast cancer, a clinical remission of HAE-nC1 seems plausible."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Solid Tumor • ER

Satisfaction with Sebetralstat for HAE Attacks in Patients Switching from Parenteral On-demand Treatments in KONFIDENT-S (ACAAI 2025) - P3 | "Abstract Introduction Here, we present interim efficacy and treatment satisfaction data from patients who switched from icatibant, pdC1INH, rC1INH, or multiple parenteral on-demand treatments to oral sebetralstat to participate in KONFIDENT-S (NCT05505916). Among the 989 attacks rated as neutral (0) or satisfied (1-3), 79 were neutral and 715 were rated as very (2) or extremely satisfied (3). Conclusion Most participants who switched from parenteral treatment were very satisfied or extremely satisfied with oral sebetralstat as an on-demand treatment."

Clinical

A Case: Hepatic Abscesses and Cholecystitis Secondary to Hereditary Angioedema (ACAAI 2025) - "Case Description A 75-year-old male with HAE type I presented with throat swelling after missing two doses of lanadelumab...Treatment consisted of icatibant, cefepime, metronidazole and bowel decompression...He improved and was discharged on omadacycline with outpatient follow-up...Upon continued symptoms, repeat imaging showed hepatic abscess development likely from bacterial translocation from gut edema and resulting cholecystitis complications 2 . This case showcases the multitude of complications that may arise in HAE patients."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gastroenterology • Gastrointestinal Disorder • Hepatology • Hereditary Angioedema • Infectious Disease

A Case of HAE-ANGPT1 Treated with berotralstat - Insights into Pathophysiology (ACAAI 2025) - "Although some patients with ANGPT1 mutations have responded to icatibant—a bradykinin B2 receptor antagonist—the role of bradykinin-generating pathways, such as the contact activation system, remains poorly understood. While ANGPT1 mutations are thought to act via endothelial dysfunction, this response suggests a role for the kallikrein-kinin system. These findings support further exploration of contact pathway inhibitors in managing this HAE subtype."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Dermatology • Hereditary Angioedema • Immunology • Otorhinolaryngology • Pulmonary Disease • Urticaria • ANGPT1

Hereditary Angioedema with Normal C1 Inhibitor Due to PLG Mutation in a Male Patient (ACAAI 2025) - "Icatibant on demand use that was very effective in treating episodes. The observation that rivaroxaban was associated with symptom improvement raises questions about the intersection of fibrinolysis and bradykinin-mediated pathways. While further research is needed, such findings may offer therapeutic insights for patients with refractory symtoms."

Clinical • Cardiovascular • Complement-mediated Rare Disorders • Gastrointestinal Disorder • Hereditary Angioedema

Deucrictibant vs. Standard of Care in Hereditary Angioedema: A Propensity Score-Matched Analysis (ACAAI 2025) - P2/3 | "MMS data (collected November 2022 until April 2023) included 29 participants (69% female; mean [range] age 41 [18-70]), with attacks most often treated with icatibant (60.2%) or C1INH concentrate (31.7%). Among 85 non-laryngeal attacks matched between the cohorts, median estimates (95% confidence intervals) for time (hours) to different outcomes of improvement were shorter for deucrictibant vs SOC on time to the following outcomes: 1.68 (1.03-1.93) vs 2.23 (1.56-3.07, p=0.0001) for PGI-C at least “a little better”, 2.93 (2.03-3.95) vs 4.56 (3.33-6.18; p=0.0005) for PGI-C at least “better”, and 2.38 (1.93-2.95) vs 4.02 (3.04-5.19; p=0.0001) for PGI-S 1-level improvement. Conclusion This PSM analysis showed that a cohort of participants with HAE in a clinical study treated with deucrictibant had more favorable outcomes on some PGI-C/S assessments than a cohort treated with SOC in an observational study."

Cardiovascular • Complement-mediated Rare Disorders • Hereditary Angioedema

The Many Faces Of Angioedema (ACAAI 2025) - "Icatibant 30mg dose was given with improvement in swelling. Hemodialysis activates the kallikrein-kinin system, increasing bradykinin. Our patient continued to have recurrent episodes related to hemodialysis, requiring prophylactic Lanadelumab."

Cardiovascular • Chronic Kidney Disease • Cystic Fibrosis • Dermatology • Genetic Disorders • Immunology • Pulmonary Disease • Renal Disease • Respiratory Diseases • Urticaria

Hereditary Angioedema With Normal C1 Esterase Inhibitor: A Case of a Late Diagnosis in a 48-Year-Old Male. (PubMed, Cureus) - "Prior treatments, including corticosteroid injections and oral prednisone, were ineffective...The patient was prescribed icatibant for acute flares and berotralstat for prophylaxis...Increased awareness of HAE-nC1-INH among clinicians is essential to improve timely diagnosis and appropriate treatment. This case underscores the importance of differentiating HAE-nC1-INH from other forms of angioedema to prevent misdiagnosis."

Journal • Cardiovascular • Complement-mediated Rare Disorders • Dyslipidemia • Epstein-Barr Virus Infections • Hereditary Angioedema • Immunology • Rare Diseases