Safety and effectiveness of tadalafil in pediatric patients with pulmonary arterial hypertension: a sub-group analysis based on Japan post-marketing surveillance

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.

Keywords:

• Pulmonary arterial hypertension
• Pediatric
• Tadalafil
• Post-marketing surveillance
• Phosphodiesterase type 5 inhibitor

Transparency

Declaration of funding

Eli Lilly Japan K.K., the manufacturer/licensee of tadalafil (Adcirca®), sponsored this surveillance.

Declaration of financial/other relationships

HY, NK, MT, NS, and MM are employed by Eli Lilly Japan K.K. KT is an employee of Nippon Shinyaku Co., Ltd, which participated in the contract, data collection, and data analysis, and that received funding from Eli Lilly Japan K.K. The authors declare that they have no other conflicts of interest, significant relationships, or financial interests related to this surveillance or to this publication. CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgments

The authors acknowledge the efforts of the investigators, and thank the healthcare providers, registered patients, and their families who participated in the surveillance. Medical writing assistance was provided by Michael H. Ossipov of inVentiv Health Clinical, LCC. Eli Lilly Japan K.K. contracted with inVentiv Health Clinical, LLC, for writing and editorial services. The services of inVentiv Health Clinical, LLC complied with international guidelines for Good Publication Practice (GPP3).