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Background: Hereditary angioedema (HAE) is associated with a substantial disease burden. Lanadelumab reduced the HAE attack rate during 132 weeks of follow-up in the HELP open-label extension (OLE) Study (NCT02741596)., Objective: To measure the impact of long-term lanadelumab treatment on patient-reported outcomes (PROs)., Methods: Rollover patients (completed the 26-week HELP study [NCT02586805]) and nonrollovers (newly enrolled) received lanadelumab 300 mg every 2 weeks. PROs (Angioedema Quality of Life Questionnaire [AE-QoL], Short Form Health Survey 12-item version 2, Hospital Anxiety and Depression Scale, Work Productivity and Activity Impairment-General Health Questionnaire, and EQ-5D-5L questionnaire) were assessed at baseline (day 0 of HELP OLE) and various time points until the end-of-study visit. The Angioedema Control Test, Treatment Satisfaction Questionnaire for Medication, and Global Impression of Treatment Response were administered starting at week 52., Results: The mean (SD) change in AE-QoL total score from baseline to end-of-study for rollovers (n = 90) was -10.2 (17.9), exhibiting further improvement from HELP in health-related quality of life (HRQoL); 48.9% of rollovers achieved the previously defined 6-point minimal clinically important difference. Nonrollovers (n = 81) reported a change of -19.5 (21.3). Controlled disease (Angioedema Control Test total score ≥10) was reported by 90.2% of rollovers and 95.9% of nonrollovers at the end of the study. Excellent treatment response was reported by 78.7% of patients and 82.4% of investigators. Results from other PROs indicated a slight improvement in anxiety, a high level of satisfaction with treatment, and increased work productivityor activity., Conclusion: Clinically meaningful improvement in HRQoL was exhibited with long-term lanadelumab treatment, supporting the benefit of lanadelumab therapy associated with attack prevention., Trial Registration: ClinicalTrials.gov Identifiers: NCT02586805 (HELP Study) and NCT02741596 (HELP open-label extension)., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To review the criteria for long-term prophylaxis therapy in patients with hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), describe how these criteria have evolved over time, and anticipate how criteria may change in the future with the availability of new C1-INH-HAE treatment options., Data Sources: Treatment guidelines, consensus statements, and expert reviews., Study Selections: Manuscripts that described long-term prophylaxis therapy in patients with C1-INH-HAE were selected., Results: Historically, patients with C1-INH-HAE were considered to be candidates for long-term prophylaxis therapy if they had at least 1 attack per month, had at least 5 days of disability per month because of C1-INH-HAE, or did not sufficiently respond to on-demand treatment. More recently, guidelines and reviews state that thresholds of number of attacks or days of disability are arbitrary and that treatment plans should be individualized to the patient's needs. Furthermore, all patients should have a comprehensive management plan that is reviewed periodically and should have at least 2 doses of on-demand treatment available. Prophylaxis therapy should be discussed as a potential treatment option for each patient; however, the decision for its use will depend on the patient's individual needs and the course of their symptoms., Conclusion: The criteria for long-term prophylaxis therapy in C1-INH-HAE have changed with the recognition that treatments should be individualized to the patient's needs and with the availability of new medications that have more favorable benefit-risk profiles, are easier to use, and improve patients' quality of life., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Effective treatment of acute attacks is critical in managing hereditary angioedema (HAE). Ecallantide, a plasma kallikrein inhibitor, is approved for the treatment of HAE attacks. Occasionally, a second dose is needed when treating attacks of HAE., Objective: To evaluate the characteristics of HAE attacks requiring a second dose (dose B) of ecallantide., Methods: Data from all ecallantide clinical trials (EDEMA2, EDEMA4, and DX-88/19) that allowed an open-label dose B were included in this analysis. Patient and attack characteristics potentially predictive of dose B after ecallantide were analyzed by logistic regression. A multivariate model was built using a backward selection process, incorporating variables from the univariate model with P < .20 and removing factors with the highest P value until only significant (P < .05) factors remained., Results: The analysis included 732 ecallantide-treated HAE attacks in 179 patients. Dose B was required in 88 attacks (12.0%), most (80.5%) for incomplete response. By attack location, 31 of 325 abdominal attacks (9.5%), 17 of 158 laryngeal attacks (10.8%), and 40 of 242 peripheral attacks (16.5%) required dose B. On the basis of the univariate analysis, baseline severity (odds ratio = 1.33, P = .15) and peripheral attack (odds ratio = 1.80, P = .01) were identified as potential predictive factors; abdominal attacks had an inverse correlation (odds ratio = 0.64, P = .055). However, the multivariate analysis identified only peripheral attacks as statistically significantly correlated (P < .05) with dose B requirement., Conclusion: A single, 30-mg dose of ecallantide was effective for most HAE attacks (88.0%). Patients with peripheral attacks of HAE were more likely to require a second dose of ecallantide after 4 hours., Trial Registration: clinicaltrials.gov Identifiers: not applicable for EDEMA2 (trial was conducted before registration requirements were implemented), NCT00457015 for EDEMA4, and NCT00456508 for DX-88/19., (Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The For Angioedema Subcutaneous Treatment (FAST)-3 study was a phase III, randomized, double-blind, placebo-controlled study of icatibant (bradykinin B(2) receptor antagonist) in subjects with hereditary angioedema (HAE) resulting from C1-INH deficiency or dysfunction (type I/II)., Objective: To investigate icatibant efficacy and safety in subjects with acute HAE attacks., Methods: Subjects with moderate to very severe cutaneous or abdominal symptoms received icatibant (n = 43) or placebo (n = 45). Five subjects with laryngeal (mild-to-moderate) first attacks received icatibant (n = 3) or placebo (n = 2), and 5 subjects with severe laryngeal first attacks received open-label icatibant., Results: Cutaneous or abdominal attacks: icatibant significantly reduced median times (vs placebo) to 50% or more reduction in symptom severity (2.0 vs 19.8 hours; P < .001, primary endpoint), onset of primary symptom relief (1.5 vs 18.5 hours; P < .001, key secondary endpoint), or almost complete symptom relief (8.0 vs 36.0 hours; P = .012) and provided a shorter time to initial symptom relief (0.8 vs 3.5 hours; P < .001). For laryngeal attacks, median time to 50% or more reduction in symptom severity was 2.5 hours (icatibant) and 3.2 hours (placebo). No icatibant-treated subject required rescue medication before symptom relief occurred. The incidence of adverse events (AEs) was similar in icatibant- and placebo-treated subjects (41% and 52%, respectively). All icatibant-treated subjects experienced injection site reactions, but none reported clinically relevant changes in safety parameters or serious AEs., Conclusions: FAST-3 demonstrated that icatibant was effective and generally well tolerated in subjects with acute HAE attacks., Trial Registration: Clinicaltrials.gov Identifier: NCT00912093., (Copyright © 2011 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Hereditary angioedema (HAE) is a genetic disorder resulting from low levels of C1-inhibitor activity that manifests as acute attacks of variable and sometimes life-threatening edema. Ecallantide is a novel potent inhibitor of human plasma kallikrein, a key mediator of the excessive formation of bradykinin associated with the signs and symptoms of an HAE attack., Objective: To evaluate the efficacy and safety of ecallantide in the treatment of acute HAE attacks., Methods: In this double-blind, placebo-controlled study, patients with a moderate to severe HAE attack were randomized 1:1 to receive 30 mg of subcutaneous ecallantide or placebo. The primary efficacy end point was change from baseline in mean symptom complex severity score 4 hours after dosing. Additional end points included treatment outcome score 4 hours after dosing and maintenance of significant overall improvement through 24 hours., Results: Ninety-six patients were enrolled. Mean (SD) change from baseline in mean symptom complex severity score 4 hours after dosing was significantly greater with ecallantide use (-0.8 [0.6]) compared with placebo use (-0.4 [0.8]) (P = .01 comparing distributions). Ecallantide therapy was also associated with a significantly larger mean (SD) treatment outcome score 4 hours after dosing vs placebo use (ecallantide: 53.4 [49.7]; placebo: 8.1 [63.2]; P = .003 comparing distributions). The benefit of ecallantide was apparent within 2 hours after dosing and was maintained through 24 hours after dosing. The safety profile was similar between the treatment groups., Conclusion: Ecallantide appears to be an effective and safe treatment for acute attacks of HAE.

Background: Inhaled corticosteroids (ICSs) delivered by metered-dose inhalers that contain chlorofluorocarbon propellants are being discontinued because of the harmful effects of chlorofluorocarbon on the ozone layer. Therefore, some metered-dose inhaler products are being reformulated with "ozone-friendly" hydrofluoroalkane propellants., Objective: To evaluate treatment with fluticasone propionate hydrofluoroalkane inhalation aerosol, 88, 220, and 440 microg twice daily, vs placebo in patients with asthma receiving an ICS., Methods: Randomized, double-blind, parallel-group, 12-week study., Results: Mean morning predose percent predicted forced expiratory volume in 1 second increased by 2.2%, 3.2%, and 4.6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, compared with an 8.3% decrease for placebo (P < .001 vs placebo for all groups). Secondary pulmonary function end points and asthma symptoms showed similar improvements compared with placebo. Discontinuation from the study due to lack of efficacy was 50% in the placebo group and 11%, 10%, and 6% in the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively. At week 12, the probability of remaining in the study was 0.89, 0.90, and 0.94 for the fluticasone propionate, 88-, 220-, and 440-microg twice-daily, groups, respectively, vs 0.45 for the placebo group (P < .001 for all). Changes in 24-hour urinary cortisol excretion rates were similar among treatment groups., Conclusions: Fluticasone propionate hydrofluoroalkane, previously shown to be a clinically suitable alternative to fluticasone propionate chlorofluorocarbon, was effective and well tolerated. The ability to switch from fluticasone propionate chlorofluorocarbon and other chlorofluorocarbon-containing ICSs to fluticasone propionate hydrofluoroalkane without sacrificing asthma control or tolerability will facilitate a smooth transition to this nonchlorofluorocarbon-containing medicinal.

Background: Previous studies have demonstrated the efficacy and safety of twice-daily budesonide Turbuhaler (Pulmicort Turbuhaler, AstraZeneca, Wilmington, DE) for the treatment of mild to severe asthma., Objective: To compare the efficacy and safety of budesonide Turbuhaler administered once daily each morning with placebo in inhaled corticosteroid-naive adults with persistent asthma., Methods: In this randomized, double-blind, placebo-controlled, multicenter study, 177 adults (aged 18 to 70 years) received placebo or once-daily budesonide Turbuhaler (400 microg) for 12 weeks. Efficacy variables included mean changes from baseline in forced expiratory volume in 1 second (FEV1) and AM/PM peak expiratory flow rate (PEFR), and nighttime/daytime asthma symptom scores, patient discontinuations, use of breakthrough medication (albuterol), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of FVC (FEF25%-75%), and quality of life assessments. Safety was evaluated based on adverse events, physical examinations, vital signs, and laboratory tests., Results: Demographic and baseline characteristics were comparable between study groups. The mean percentages of predicted FEV1 at baseline were 71.9 +/- 9.8 in patients receiving budesonide Turbuhaler and 70.6 +/- 11.0 in patients receiving placebo. Mean changes from baseline over the 12-week treatment period in FEV1 were significantly (P = 0.007) improved in patients receiving once-daily budesonide Turbuhaler compared with placebo (0.31 L and 0.17 L, respectively). Significant (P < or = 0.037) improvements over placebo also were observed in AM PEFR, nighttime/daytime asthma symptoms, and albuterol use with budesonide Turbuhaler treatment. Adverse events were generally mild or moderate in intensity and similar between study groups., Conclusions: Budesonide Turbuhaler 400 microg administered once daily in the AM is efficacious and safe for inhaled corticosteroid-naive asthmatic adults.