Effects of tolvaptan discontinuation in patients with autosomal dominant polycystic kidney disease: a post hoc pooled analysis

BMC Nephrology

Research

Holly B. Krasa¹  Sasikiran Nunna²  Dorothee Oberdhan²  Ancilla W. Fernandes²  Xiaolei Zhou³  Eric Davenport³  Michael Lioudis⁴ 

[1] Blue Persimmon Group LLC, 1701 Rhode Island Ave NW, 20036, Washington, DC, USA;Otsuka Pharmaceutical Development & Commercialization, Inc, 508 Carnegie Center Drive, 08540, Princeton, NJ, USA;RTI Health Solutions, PO Box 12194, 3040 East Cornwallis Road, 27709, Research Triangle Park, NC, USA;Section of Nephrology, Upstate Medical University, 343 Campus West Building (CWB), 750 East Adams Street, 13210, Syracuse, NY, USA;

关键词: Autosomal dominant polycystic kidney disease (ADPKD);    Tolvaptan;    Glomerular filtration rate;    Kidney volume;    Clinical trial;    Treatment;   

DOI  :  10.1186/s12882-023-03247-6

 received in 2023-02-28, accepted in 2023-06-19,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundTolvaptan slows kidney function decline in patients with autosomal dominant polycystic kidney disease (ADPKD) who are at risk of rapid progression. Given that treatment requires commitment to long-term use, we evaluated the effects of tolvaptan discontinuation on the trajectory of ADPKD progression.MethodsThis was a post hoc analysis of pooled data from two clinical trials of tolvaptan (TEMPO 2:4 [NCT00413777] and TEMPO 3:4 [NCT00428948]), an extension trial (TEMPO 4:4 [NCT01214421]), and an observational study (OVERTURE [NCT01430494]) that enrolled patients from the other trials. Individual subject data were linked longitudinally across trials to construct analysis cohorts of subjects with a tolvaptan treatment duration > 180 days followed by an off-treatment observation period of > 180 days. For inclusion in Cohort 1, subjects were required have ≥ 2 outcome assessments during the tolvaptan treatment period and ≥ 2 assessments during the follow-up period. For Cohort 2, subjects were required to have ≥ 1 assessment during the tolvaptan treatment period and ≥ 1 assessment during the follow-up period. Outcomes were rates of change in estimated glomerular filtration rate (eGFR) and total kidney volume (TKV). Piecewise-mixed models compared changes in eGFR or TKV in the on-treatment and post-treatment periods.ResultsIn the Cohort 1 eGFR population (n = 20), the annual rate of eGFR change (in mL/min/1.73 m2) was -3.18 on treatment and -4.33 post-treatment, a difference that was not significant (P = 0.16), whereas in Cohort 2 (n = 82), the difference between on treatment (-1.89) and post-treatment (-4.94) was significant (P < 0.001). In the Cohort 1 TKV population (n = 11), TKV increased annually by 5.18% on treatment and 11.69% post-treatment (P = 0.06). In Cohort 2 (n = 88), the annual TKV growth rates were 5.15% on treatment and 8.16% post-treatment (P = 0.001).ConclusionsAlthough limited by small sample sizes, these analyses showed directionally consistent acceleration in measures of ADPKD progression following the discontinuation of tolvaptan.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

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Fig. 7