Abstract: PO1537
Canadian Real-World Assessment of Tolvaptan in ADPKD: C-MAJOR Study and Safety Monitoring and Distribution Program
Session Information
- Cystic Kidney Diseases: Mechanisms, Genetics, and Treatment
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- McFarlane, Philip, St Michael's Hospital, Toronto, Ontario, Canada
- Parfrey, Patrick S., Memorial University of Newfoundland, St. John's, Newfoundland, Canada
- Bichet, Daniel G., Universite de Montreal, Montreal, Quebec, Canada
- Bergeron, Luc, Otsuka Canada Pharmaceutical Inc., Montreal, Quebec, Canada
- Laplante, Annick, Otsuka Canada Pharmaceutical Inc., Montreal, Quebec, Canada
Background
Tolvaptan is the only approved treatment in Canada for slowing renal function decline and kidney enlargement in ADPKD patients. As per Health Canada requirement, a patient registry evaluating long-term clinical outcomes (C-MAJOR study) and a hepatic safety monitoring and distribution program (HSMDP) to mitigate risk of liver injury were implemented and have been ongoing for 5 years. The aim of this interim analysis is to describe baseline characteristics of patients at initiation of tolvaptan through the C-MAJOR study and to report on treatment persistence and liver transaminases elevation rate through the HSMDP.
Methods
C-MAJOR is a non-interventional, multi-centre study of ADPKD patients treated with tolvaptan. HSMDP ensures tolvaptan is dispensed under controlled liver function monitoring.
Results
As of April 2020, 398 patients, 51% female, were enrolled in C-MAJOR. At baseline, mean (SD) age was 45.1 (11.5) years, BP was 129.4 (13.4)/83.1 (10.0) mmHg and eGFR was 63.6 (27.8) mL/min/1.73 m2. Total kidney volume was 1949 (1562) mL, 80.7% of patients had a family history of ADPKD and 39.4% had a family history of early end-stage renal disease. As per Mayo classification, 90.2% were at high risk of disease progression (1C-D-E). The most common ADPKD clinical manifestations were hypertension (83.2%), hepatic cysts (69.6%) and kidney pain (24.1%). Over a mean (SD) follow-up of 2.0 (1.0) years, adverse events were reported in 82.7% of patients, most common being polyuria (19.6%), fatigue (18.6%), and nocturia (15.1%).
Over a mean (SD) follow-up of 23.0 (17.6) months in the HSMDP, 2.4% (39) of the 1,600 patients who received at least one shipment of tolvaptan reported an elevation of transaminases >3x ULN. There were 0.3% (5) of patients meeting the guidelines for permanent discontinuation. No cases of drug-induced liver injury were reported. Treatment discontinuation rates at 12, 24 and 36 months were 14%, 21% and 26%, respectively.
Conclusion
This analysis provides Canadian real-world evidence of high-risk disease progression at tolvaptan initiation, 3-y persistence data similar to phase III study and the HSMDP showing tolvaptan was permanently discontinued in 0.3% of patients because of hepatic effects.
Funding
- Commercial Support – Otsuka Canada Pharmaceutical Inc.