EIGHT YEARS OF CANADIAN REAL-WORLD ASSESSMENT OF TOLVAPTAN IN ADPKD: PATIENT REPORTED OUTCOMES FROM THE C-MAJOR STUDY

Tolvaptan (Jinarc®) is the first approved treatment in Canada to slow the progression of kidney enlargement and kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD). C-MAJOR is an ongoing, observational, multi-center registry of people with ADPKD treated with tolvaptan, initiated in 2015, as per Health Canada requirements. This analysis describes the impact of tolvaptan on ADPKD-related health-related quality of life (HRQoL) in people with ADPKD in Canada.

C-MAJOR includes patients initiating tolvaptan post-enrolment and those on-treatment at enrolment. Newly initiated patients completed patient-reported outcome (PRO) questionnaires including the Short-Form 12 Health Survey version 2 (SF-12v2), ADPKD-Impact Scale (ADPKD-IS), and ADPKD-Pain and Discomfort Scale (ADPKD-PDS). Repeated measures general linear models with mixed effects evaluated PRO changes from baseline over time, assessed at 6-month intervals.

As of 31 December 2023, 470 patients were treated with tolvaptan and included in C-MAJOR. Of these, 185 patients newly initiated tolvaptan (mean follow-up time of 53.4 months) and 113 completed PROs at baseline. Among newly initiated patients, mean age at ADPKD diagnosis and tolvaptan initiation was 29 and 43 years, respectively, 53% were female and 83% were Caucasian. Patients had a mean baseline total kidney volume of 1867 mL, kidney length of 18 cm, and an estimated glomerular filtration rate of 68 ml/min/1.73 m2 (Table 1). Of these, 77% had early chronic kidney disease (CKD; stage 1-3a) and 90% were identified as fast progressors (Mayo class 1C-E), similar to the total population (Table 1). PRO completers had mean baseline PRO scores indicative of minimally impacted HRQoL (Table 2), with generally comparable scores reported for those with early- (1-3a) and late- (3b-4) stage CKD. Despite disease progression, PRO scores generally remained stable over time. Although statistically significant changes were seen in SF-12 Physical Component Summary score (PCS; β=-0.055, p=0.002), ADPKD-IS physical and emotional scale scores (both β=0.006, p<0.001), and ADPKD-PDS Dull Pain (0.005) and Discomfort (0.004) Interference scores (both p<0.01), small effect sizes were likely not clinically meaningful (Table 3). Patients with early vs late stage CKD had, on average, greater improvements in SF-12 PCS (1.8, p=0.038), ADPKD-IS physical (-0.19), fatigue (-0.25), and emotional scale scores (-0.44, all p<0.01), ADPKD-PDS Sharp Pain (-0.33) and Overall Pain and Discomfort Severity (-0.15), and Dull Pain (-0.19) and Discomfort Interference (-0.20, all p<0.05; Table 3). A notable decline in PRO completion rates (baseline n: 111-113; 36 months n: 41-42) resulted in small sample size at later assessments, limiting interpretation.

This first report of PRO data from C-MAJOR helps inform our understanding of ADPKD impact in patients treated with tolvaptan in Canada. Findings showed people with ADPKD at early-stage CKD had minimally impacted ADPKD-related burden of illness at baseline, with PRO scores remaining constant over time with treatment despite disease progression. Greater improvements in PROs were seen for patients with early- vs late- stage CKD. Rates of PRO completion declined over an extended timeframe, highlighting challenges of gathering such data in real-world settings.