Centralized care model for hereditary angioedema overcomes geographical barriers.

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 ß -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.

Berotralstat in hereditary angioedema due to C1 inhibitor deficiency: first real-world evidence from a Canadian center.

Background: Hereditary angioedema due to C1 inhibitor deficiency is a rare genetic condition that causes recurrent swelling with consequent functional impairment and decreased quality of life. Long-term prophylaxis (LTP) to prevent angioedema episodes is a key component of disease management. Berotralstat, an oral, once-daily plasma kallikrein inhibitor, was approved for LTP by Health Canada in 2022. Methods: We conducted a retrospective, real-world study investigating the effectiveness and adverse effects of berotralstat. Data on angioedema frequency, disease control, and adverse events were tabulated. Patient satisfaction with treatment was scored on a 5-point Likert scale, with 1 representing very unsatisfied and 5 representing very satisfied with therapy. Results: From June, 2022 and May, 2023, 8 patients with HAE type 1 or type 2 received berotralstat. Effectiveness data were available for 7 patients who continued the drug for at least 3 months, 4 of whom switched to berotralstat from plasma-derived C1 inhibitor LTP. In these 7 patients, the average number of attacks per month decreased from 3.3 to 1.6 (p<0.05), representing a ~52% reduction in attack frequency. Median angioedema control test score numerically improved from 8 to 13 (p=0.0781). Of the 8 patients who received berotralstat, 3 reported no adverse effects and 5 experienced gastrointestinal side effects, which were mild and transient in 3 and led to discontinuation in 1. Average treatment satisfaction was between satisfied and very satisfied at 4.3. Conclusion: Berotralstat is an effective agent for long-term prophylaxis in HAE. Most patients experienced no adverse effects or mild, transient gastrointestinal symptoms.

Investigation of a synonymous mutation in Btk in a patient with agammaglobulinemia: A case report.

BACKGROUND: X-linked agammaglobulinemia (XLA) is the most common form of agammaglobulinemia and is caused by mutations in Btk, which encodes Bruton tyrosine kinase (BTK). CASE DESCRIPTION: We describe a 36-year-old male who presented as an infant with hypogammaglobulinemia and sinopulmonary infections and was initially diagnosed with common variable immunodeficiency. Genetic testing showed he was hemizygous for Btk c.240G > A. This synonymous variant affecting the last nucleotide of exon 3 leads to aberrant splicing of most but not all mRNA transcripts. CONCLUSION: We demonstrated reduced BTK protein expression confirming the pathogenicity of the variant and related our findings to genotype-phenotype relationship studies ina XLA caused by synonymous mutations.