Longer dupilumab dosing intervals in adult patients with atopic dermatitis: experience from a French multicentre retrospective cohort study

International audienceAbstract Background Hereditary angioedema (HAE) is associated with a heavy burden of illness. Objective To evaluate use of lanadelumab in a French Authorization for Temporary Use (ATU) program. Methods ATU requests were made between October 12, 2018, and March 13, 2019; patients were followed through September 23, 2019. At entry, patients received lanadelumab 300 mg every 2 weeks. HAE attack characteristics were evaluated at day (D) 0 and months (M) 3 and 6. Patients completed the Angioedema Quality of Life (AE-QoL) questionnaire at initiation and monthly and the Angioedema Activity Score questionnaire daily in 28 day cycles (AAS28). Results In total, 77 patients received ≥ 1 lanadelumab dose; 69 had ≥ 1 quarterly follow-up visit (analyzed population). Mean (standard deviation [SD]) lanadelumab exposure was 240.4 (53.7) days. Lanadelumab dose was modified in 12 patients (mostly to every 4 weeks). For the analyzed population, compared with attacks/month (mean [SD]) within 6 months before ATU (2.68 [2.54]), fewer attacks occurred between initiation and first visit (0.16 [0.42]; P < 0.001) or last visit (0.16 [0.42]; P < 0.001); D15 and last visit (0.15 [0.41]); and D70 and last visit (0.17 [0.70]). AE-QoL total and domain scores were significantly higher at initiation versus M3 and M6; 55% and 65% of patients, respectively, achieved a minimal clinically important difference from D0 to M3 and D0 to M6. Proportion of patients with AAS28 of 0 was higher during M3 (90%) and M6 (83%) than initiation (59%). The most frequently reported adverse events included headache (7.3%) and injection site pain (6.3%). Conclusions Lanadelumab reduced attack rates, improved quality of life, and was generally well tolerated

Long-term prophylaxis with lanadelumab for HAE: authorization for temporary use in France

International audienceBackground: Hereditary angioedema (HAE) is associated with a heavy burden of illness. Objective: To evaluate use of lanadelumab in a French Authorization for Temporary Use (ATU) program. Methods: ATU requests were made between October 12, 2018, and March 13, 2019; patients were followed through September 23, 2019. At entry, patients received lanadelumab 300 mg every 2 weeks. HAE attack characteristics were evaluated at day (D) 0 and months (M) 3 and 6. Patients completed the Angioedema Quality of Life (AE-QoL) questionnaire at initiation and monthly and the Angioedema Activity Score questionnaire daily in 28 day cycles (AAS28). Results: In total, 77 patients received ≥ 1 lanadelumab dose; 69 had ≥ 1 quarterly follow-up visit (analyzed population). Mean (standard deviation [SD]) lanadelumab exposure was 240.4 (53.7) days. Lanadelumab dose was modified in 12 patients (mostly to every 4 weeks). For the analyzed population, compared with attacks/month (mean [SD]) within 6 months before ATU (2.68 [2.54]), fewer attacks occurred between initiation and first visit (0.16 [0.42]; P < 0.001) or last visit (0.16 [0.42]; P < 0.001); D15 and last visit (0.15 [0.41]); and D70 and last visit (0.17 [0.70]). AE-QoL total and domain scores were significantly higher at initiation versus M3 and M6; 55% and 65% of patients, respectively, achieved a minimal clinically important difference from D0 to M3 and D0 to M6. Proportion of patients with AAS28 of 0 was higher during M3 (90%) and M6 (83%) than initiation (59%). The most frequently reported adverse events included headache (7.3%) and injection site pain (6.3%). Conclusions: Lanadelumab reduced attack rates, improved quality of life, and was generally well tolerated

Oral Plasma Kallikrein Inhibitor for Prophylaxis in Hereditary Angioedema.

BACKGROUND Hereditary angioedema is a life-threatening illness caused by mutations in the gene encoding C1 inhibitor (also called C1 esterase inhibitor) that lead to overactivation of the kallikrein-bradykinin cascade. BCX7353 is a potent oral small-molecule inhibitor of plasma kallikrein with a pharmacokinetic and pharmacodynamic profile that may help prevent angioedema attacks. METHODS In this international, three-part, dose-ranging, placebo-controlled trial, we evaluated four doses of BCX7353 (62.5 mg, 125 mg, 250 mg, and 350 mg once daily) for the prevention of angioedema attacks over a 28-day period. Patients with type I or II hereditary angioedema with a history of at least two angioedema attacks per month were randomly assigned to BCX7353 or placebo. The primary efficacy end point was the number of confirmed angioedema attacks. Key secondary end points included angioedema attacks according to anatomical location and quality of life. RESULTS A total of 77 patients underwent randomization, 75 received BCX7353 or placebo, and 72 completed the trial. The rate of confirmed angioedema attacks was significantly lower among patients who received BCX7353 at daily doses of 125 mg or more than among those who received placebo, with a 73.8% difference at 125 mg (P<0.001). Significant benefits with respect to quality-of-life scores were observed in the 125-mg and 250-mg dose groups (P<0.05). Gastrointestinal adverse events, predominantly of grade 1, were the most commonly reported adverse events, particularly in the two highest BCX7353 dose groups. CONCLUSIONS Once-daily oral administration of BCX7353 at a dose of 125 mg or more resulted in a significantly lower rate of attacks of hereditary angioedema than placebo. Mild gastrointestinal symptoms were the principal side effect. (Funded by BioCryst Pharmaceuticals; APeX-1 ClinicalTrials.gov number, NCT02870972 .)

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes