Hiroyoshi Yamazaki1, Noriko Kobayashi2, Masanori Taketsuna3, Koyuki Tajima4, Nahoko Suzuki5, Masahiro Murakami6. 1. a Global Patient Safety Japan , Quality & Patient Safety, Eli Lilly Japan K.K. , Kobe , Japan. 2. b Post Marketing Study Management, Medicines Development Unit Japan , Eli Lilly Japan K. K. , Kobe , Japan. 3. c Statistical Sciences, Medicines Development Unit Japan , Eli Lilly Japan K.K. , Kobe , Japan. 4. d Post Marketing Surveillance Clinical Research Department , Nippon Shinyaku CO., Ltd , Kobe , Japan. 5. e Biometrics, Medicines Development Unit Japan , Eli Lilly Japan K.K. , Tokyo , Japan. 6. f Medical Science, Medicines Development Unit Japan , Eli Lilly Japan K.K. , Kobe , Japan.
Abstract
OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. METHODS: This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. RESULTS: The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. CONCLUSION: This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.
OBJECTIVE: To evaluate the long-term safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension (PAH) in real-world clinical practice. METHODS: This is an observational surveillance of PAH patients receiving tadalafil in the contracted sites. A sub-group analysis was performed of 391 pediatric PAH patients (<18 years) who were included from 1,704 total patients in this surveillance. Safety was assessed from the frequency of adverse drug reactions (ADRs), discontinuations due to adverse events (AEs), and serious adverse drug reactions (SADRs). Effectiveness measurements included change in World Health Organization (WHO) functional classification of PAH, cardiac catheterization (pulmonary arterial pressure: PAP), and echocardiography (tricuspid regurgitation pressure gradient: TRPG). Survival rate was also measured. RESULTS: The mean patient age was 5.7 ± 5.34 years. Associated PAH (APAH) and idiopathic PAH (IPAH) accounted for 76.0% and 17.6%, respectively, of the PAH patients. Patients were followed for up to 2 years. Among 391 patients analyzed for safety, the overall incidence rate of ADRs was 16.6%. The common ADRs (≥ 1%) were headache (2.8%), hepatic function abnormal, platelet count decreased (1.3% each), and epistaxis, (1.0%). Eleven patients (2.8%) reported 16 SADRs. Three patients died secondary to SADRs. For the effectiveness analysis, the incidence of WHO functional class improvement at 3 months, 1 year, and 2 years after the initiation of tadalafil and last observation in pediatric patients were 16.5%, 19.7%, and 16.3%, respectively. Both PAP and TRPG showed a statistically significant reduction at last observation. CONCLUSION: This manuscript reveals the use of tadalafil in the real-world pediatric population with an acceptable safety profile in Japan.
Authors: Dunbar Ivy; Damien Bonnet; Rolf M F Berger; Gisela M B Meyer; Simin Baygani; Baohui Li Journal: Pulm Circ Date: 2021-06-23 Impact factor: 3.017