Constance H. Katelaris

Description:eficiency, HAE-nC1INH patients are at risk of serious morbidity and mortality. Therefore, proactive management and treatment of HAE-nC1INH patients after an expert physician diagnosis is critically important. The underlying pathophysiology responsible for the angioedema has also been clarified in some of the HAE-nC1INH types. While several clinical guidelines and practice parameters including HAE-nC1INH have been published, we have made substantial progress in our understanding encompassing diagnostic criteria, pathophysiology, and treatment outcomes. HAE International (HAEi) and the US HAE Association (HAEA) convened a symposium of global HAE-nC1INH experts to synthesize our current knowledge in the area. Given the paucity of high-level evidence in HAE-nC1INH, all recommendations are based on expert opinion. This review and expert opinion on the best practice approach to diagnosing and treating HAE-nC1INH will support physicians to better manage patients with HAE-nC1INH.

Description:Background: Hereditary angioedema (HAE) attacks substantially impair health-related quality of life (HRQoL). Current World Allergy Organization and the European Academy of Allergy and Clinical Immunology guidelines goals include complete control and normalization of patients' lives. Garadacimab (anti-activated factor XII monoclonal antibody) reduced the mean attack rate after first administration in the pivotal phase III (VANGUARD; NCT04656418) and ongoing long-term phase III open-label extension (OLE) (NCT04739059) studies. Objective: To report exploratory HRQoL data from the interim analysis of the phase III OLE study (data cutoff February 13, 2023). Methods: Patients ages ≥12 years and with HAE received garadacimab 200 mg subcutaneously once monthly in the OLE study. The patient population comprised patients who were garadacimab naive (received placebo in the previous phase III study and newly enrolled patients) and patients who received garadacimab in previous phase II/III studies. The Angioedema Quality of Life (AE-QoL) questionnaire, Treatment Satisfaction Questionnaire for Medication version II (TSQM II), and Work Productivity and Activity Impairment: General Health (WPAI:GH) questionnaire were administered at baseline and every 3 months during the OLE study. AE-QoL and TSQM II scores were evaluated in comparison with minimal clinically important differences (MCID). Results: Overall, 90 patients who were garadacimab naive and 71 patients with previous garadacimab exposure received garadacimab in the phase III OLE study. The mean ± standard deviation AE-QoL total score improved by 34.2 ± 18.8 points in patients who were garadacimab naive and by 2.3 ± 13.1 points further to the reduction experienced in patients with previous garadacimab exposure. The AE-QoL MCID was met by 92.1% of patients who were garadacimab naive; 81.6% of patients with previous garadacimab exposure experienced stable AE-QoL scores or further improvements per MCID. TSQM II scores were improved from day 1 with garadacimab and sustained to month 12. Improvements in WPAI:GH scores were consistent with AE-QoL and TSQM II. Conclusion: Garadacimab elicited clinically meaningful long-term improvements in HRQoL, work productivity, and treatment satisfaction in patients with HAE, which brought them closer to complete disease control and normalization of life.Clinical trial NCT04739059, clinicaltrials.gov.

Description:Background: Anaphylaxis is an acute, severe, and potentially fatal reaction marked by the fast onset of symptoms and organ involvement that may lead to death from vascular collapse or airway obstruction. Despite adrenaline (epinephrine) being the first-line medication for reversing anaphylactic symptoms, misconceptions about its safe and correct use persist and lead to improper administration. Methods: This review provides a comprehensive overview of clinical use of adrenaline autoinjectors (AAIs) in the management of anaphylaxis, key safety considerations, and pharmacokinetic/pharmacodynamic profile of three of the currently marketed AAIs. Results: When administered intramuscularly (IM) at the recommended dose for anaphylaxis, adrenaline is considered safe; however, adequate training in emergency care is essential to minimize dosage errors and mitigate safety risks. In specific situations, such as refractory anaphylaxis, intravenous (IV) administration is advised under specialized settings due to the potential risk of severe cardiovascular complications that can result from dosing errors. Conclusions: Although adrenaline can cause mild and transient side effects even when administered correctly at the recommended dosage, the potential side effects should not deter its use in critical situations such as anaphylaxis. This review aims to highlight the role of AAIs in improving patient outcomes during anaphylactic emergencies.

Description:Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by painful and potentially life-threatening tissue swelling due to a deficiency or dysfunction of the C1 esterase inhibitor protein. Despite the availability of comprehensive on-demand treatment guidelines, compliance to guideline recommendations remains suboptimal, resulting in persisting unmet need. Methods: This observational, online survey was conducted between September 6, 2022, and October 19, 2022 to understand the behaviors and perspectives of individuals in the US with hereditary angioedema (HAE). Participants were recruited by the US Hereditary Angioedema Association and were eligible if they were US residents with clinician-diagnosed HAE type I or II and had experienced at least one HAE attack. The survey included multiple-choice, rank-order, and scale-based responses using a 5-point Likert scale for agreement and an 11-point Likert scale for anxiety. Statistical analysis was performed using Microsoft Excel, summarizing continuous variables as means, medians, and ranges, and categorical variables as frequency distributions and percentages. Results: A total of 107 out of 155 participants completed the survey (mean age = 41 years; 80.4% female). Half of the respondents used both prophylaxis and on-demand therapy, while the other half used on-demand therapy only. Icatibant was the most commonly used on-demand treatment (78.5%). The survey revealed that 57% of respondents did not treat all HAE attacks, and only 14% treated attacks immediately. Delays in treatment were common, with a mean time to treatment of 2.4 h, and younger patients were less likely to carry on-demand treatment. Reasons for delaying treatment included the perceived severity of the attack, lack of on-demand treatment availability, and pain associated with treatment. Additionally, 32.7% of respondents experienced the return of an HAE attack after initial treatment, with those delaying treatment more likely to experience recurrence. The survey also found that delayed treatment led to more severe attacks and longer recovery times, impacting work, social activities, and overall quality of life. Conclusions: Although guidelines recommend early treatment of HAE attacks, many respondents do not treat immediately. This finding underscores the importance of incorporating open patient-physician communication to improve guideline compliance and the management of HAE.

Description:Treatment targets in severe asthma have evolved towards a remission-focused paradigm guided by precision medicine. This novel concept requires a shift from evaluating the efficacy of therapies based on a single outcome at a single time point to an outcome that captures the complexity of asthma remission involving several domains assessed over a sustained period. Since the concept is still emerging, multiple definitions have been proposed, ranging from symptom control and exacerbation-free to resolution of underlying pathobiology, with varying rigour in each parameter. Understanding the strengths and weaknesses of the current construct is needed to progress further. We conducted a roundtable discussion with 27 asthma experts to address this issue, and discussions were narratively synthesised and summarised. The participants observed that between one in three and one in five people treated with targeted biological therapies or macrolides experience low disease activity over a sustained period. They unanimously agreed that labelling the attained clinical state as clinical remission is useful as a clinical (e.g., facilitating a treat-to-target approach), policy (e.g., widening eligibility criteria for biologics), and scientific (e.g., a path to understanding cure) tool. Current remission rates vary significantly due to definition variability. When assessing remission, it is essential to consider confounding factors (e.g., steroid use for adrenal insufficiency). More research is required to reach an acceptable definition, and including the patient's voice in such research is essential. In conclusion, the concept of treatment-induced clinical remission is possible and valuable in asthma. However, further refinement of the definition is required.