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Kidney Week

Abstract: SA-PO480

Canadian Real-Life Assessment of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease (ADPKD): C-MAJOR Study and Hepatic Safety Monitoring Program

Session Information

  • ADPKD: Clinical Studies
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • McFarlane, Philip, St. Michael's Hospital, Toronto, Ontario, Canada
  • Bichet, Daniel G., University of Montreal, Montreal, Quebec, Canada
  • Bergeron, Luc, Otsuka Canada Pharmaceutical Inc., Saint-Laurent, Quebec, Canada
  • Laplante, Annick, Otsuka Canada, Saint-Sauveur, Quebec, Canada
Background

Tolvaptan is the only treatment slowing renal function decline, kidney enlargement and progression to end-stage renal disease in ADPKD. Health Canada mandated a patient registry of long-term clinical outcomes and a hepatic safety monitoring and distribution program (HSMDP) to mitigate the risk of liver injury. The objectives were to describe the baseline characteristics, quality of life (QoL), adherence, liver profile elevation rates and overall safety profile of patients enrolled in the real life setting of these two programs.

Methods

This is the 3rd interim analysis of C-MAJOR, the Canadian, non-interventional registry of ADPKD patients treated with tolvaptan and the 1st analysis of the HSMDP documenting the appropriate laboratory monitoring of hepatic function.

Results

1143 and 250 patients were included in the HSMDP and C-MAJOR, respectively. At tolvaptan initiation, hypertension (77%), hepatic cysts (63%), and renal pain (21%) were the most common ADPKD manifestations. Patients presented with chronic kidney disease (CKD) Stage 1 (16%), 2 (28%), 3a (24%), 3b (20%) and 4 (8%) and with family history of ADPKD (77%) and family history of early ESRD (36%). At treatment initiation, 87 % of patients were considered at high risk of disease progression as per the Mayo classification (1C, D or E).

QoL was assessed in newly initiated tolvaptan patients. Although not significantly different, progressively severe ADPKD-Pain and Discomfort Scale and Impact Scale scores in all domains were observed for increasing CKD stage.

Over a mean (SD) follow-up of 64.1 (43.0) weeks, 3.1% of the 941 patients on tolvaptan experienced an elevation of LFT >3 X ULN. No cases of drug-induced liver injury were reported. The 6, 12 and 24-month treatment persistence rates on tolvaptan were 89.2%, 83.9% and 77.9% respectively. 47% of patients experienced an adverse event, most commonly nocturia (12%), polydipsia (9%), hypertension (8%), dizziness (7%), polyuria (6%) and fatigue (5%).

Conclusion

This interim report on real-life utilization of tolvaptan in Canada provides evidence of advanced disease at treatment initiation. The safety profile and persistence rate are similar to that reported in clinical trials. The liver safety evidence demonstrates that the HSMDP is effective in mitigating the risks to the patients.

Funding

  • Commercial Support