#2861 Real-life efficacy of tolvaptan for polycystic kidney disease (PKD) and association with patient adherence in London North-West specialist clinic
Authors: Solanki Gina , Mohamedali Zahra , Tse Cecilia , Teles Joana , Sawyer Janet , Sharma Bindu , Shahid Kainat , Sandhu Eleanor , Goel Shruti , Tanna Anisha , Ashby Damien , Duncan Neill 
Published: May 2024

Background and Aims

Tolvaptan is approved by NICE in the treatment of PKD afterrandomised controlled trials demonstrated a reduction in decline in eGFR. Aquaresis occurs as an effect, and this may limit tolerability as the second dose in a day causes nocturia and disturbed sleep. Thirty-three patients in our specialist PKD clinic were treated based on criteria of bipolar renal length &gt;=15cm and decline in eGFR by &gt; −5 ml/min/yr. We evaluated their real-life outcome regarding measures of adherence including an adapted Basel Assessment of Adherence to Immunosuppressive Medication Scale © (by permissions.nursing.unibas.ch/) originally validated for immunosuppression medications in transplant patients. A further 24 patients had finished treatment at our centre and were excluded as BAASIS could not be applied in hindsight. However, they illustrated a notably high level of intolerance leading to cessation in 16/24 (9 with nocturia, 4 transaminitis, 1 angioedema, 1 rash, 1 fatigue) emphasizing the importance of this work on adherence and response.

Method

BAASIS addresses recall of treatment adherence in the preceding 4 weeks, all 33 patients currently treated as of 16/1/24 were screened on telephone by two independent auditors with a standard non-judgemental introductory script designed to result in candid engagement. Investigators were blinded to renal outcomes. A decline in eGFR of less than 5 ml/min/yr was defined as treatment response.

Results

Of the 33 patients included, 14 males and 19 females, median age 49yrs (range 32-72), were on treatment for a mean of 2.7yr (SD 2.2, range 0.3-7.5). Mean eGFR (CKD-EPI) was 58 ml/min (SD 19, range 28-110) at start and 48 ml/mi (SD 23, range 17-102) at end of treatment. Median total daily dose was 120 mg/d (range 60-120). Attendance at clinic for monitoring was 100%. 18/33 patients had responded to treatment, with delta eGFR –0.1 ml/min/year (SD 3.4) versus non-responders’' delta eGFR –13 ml/min/year (SD 8.7)

There was a total of 35 instances of non-implementation in 23/33 patients with missed (20 instances), delayed (13 instances) or self-alteration in doses (2 instances). Only 10/33 patient made no failure to implement Tolvaptan at any time. There were 9 patients with non-persistence of Tolvaptan treatment.

Associative analysis of renal outcome with adherence was made for all 31 patients who had more than 6 months treatment, 2 patients being excluded because treatment had been too short-term. 25/31 had non-adherence defined by non-implementation or non-persistence or both, but this did not statistically associate with treatment failure ChiSq 1.951 p = 0.16. The element of non-implementation alone was however associated with treatment failure ChiSq 4.949 p = 0.03, this term includes patient behaviour of not taking and mistiming drug taking, and patient-initiated dose reduction and drug holidays.

Conclusion

Just over half (55%) of currently treated patients had made a clinical response to Tolvaptan. 23/33 patients had non-implementation within the 4 weeks preceding the validated adherence survey, and this was significantly associated with treatment failure. This study is limited to a small single-centre patient cohort but could easily be applied more widely. This study informs shared-decision making and we should encourage our patients to take this high-cost drug in the right amount and at the right times, and notably not to miss doses, thereby to achieve higher clinical response rates.