Regional variation in tolvaptan prescribing across England: national data and retrospective evaluation from an expert centre

Background Tolvaptan, a vasopressin V2 receptor antagonist, was approved in 2015 by the UK National Institute for Health and Care Excellence for use in patients with autosomal dominant polycystic kidney disease (ADPKD) and rapid disease progression. Simultaneous guidance was issued by the UK Kidney Association (UKKA) to facilitate national implementation. Methods Data on tolvaptan prescribing in England was obtained through the National Health Service (NHS) Digital, a national survey of all 77 adult kidney units, and the implementation of UKKA guidance was evaluated at an expert PKD centre. Results A regional variation of up to 4-fold for tolvaptan prescribing in England was found. Despite most kidney units following UKKA guidance, centre-based estimates of eligible or treated patient numbers were highly variable. Retrospective evaluation at an expert PKD centre revealed that in a cohort demonstrating rapid estimated glomerular filtration rate (eGFR) decline, 14% would not be eligible for tolvaptan by Mayo imaging classification and more than half (57%) would not be eligible by Predicting Renal Outcome in Polycystic Kidney Disease score. The 3-year discontinuation rate was higher than expected (56%), the majority (70%) due to aquaretic symptoms. In patients taking tolvaptan for at least 2 years, 81% showed a reduction in the rate of eGFR decline compared with baseline, with earlier disease associated with positive treatment response. Conclusion Real-world data have revealed a much higher regional variation in tolvaptan prescribing for ADPKD in England than expected. We propose further investigation into the factors responsible for this variation.