BACKGROUND: The efficacy and safety of tolvaptan in adults with ADPKD was initially established in a 3-year phase 3 clinical trial (TEMPO 3:4; NCT00428948). Tolvaptan was approved in the United States in 2018 for patients with ADPKD at high risk of progression. A published ADPKD progression model predicted longer-term outcomes including eGFR decline and time to ESRD. The model incorporated an equation used to predict eGFR based on Mayo subclasses 1C, 1D, and 1E as indicators of rapid progression. To estimate treatment benefit, long-term outcomes were modelled for patients treated with and without tolvaptan based on the TEMPO 3:4 cohort.
METHODS: In the base case, the annual absolute reduction in eGFR decline for tolvaptan versus placebo of 1.2 ml/min/1.73m2 was applied to the predicted rates of eGFR decline in the absence of treatment. Additionally, in a sensitivity analysis based on a post-hoc analysis of TEMPO 3:4, the effect on eGFR decline by subclass 1C, 1D, and 1E was applied. CKD progression and time to ESRD were estimated for both cohorts.
RESULTS: The predicted time to ESRD was longer for all patients in CKD stages 1-3 treated with tolvaptan, with greater estimated absolute benefit when treatment was initiated for patients in early CKD stages (Image).
CONCLUSION: The model estimates that patients treated with tolvaptan versus no treatment spend more time in earlier CKD stages and later onset of ESRD. Results were consistent across CKD stages and Mayo subclasses. Findings highlight the potential long-term value of early intervention with tolvaptan in patients at risk of rapid ADPKD progression.
