Abstract: PUB207
Comparative Effectiveness of Disease-Modifying Agents in Patients with ADPKD: A Systematic Review and Network Meta-Analysis
Session Information
Category: Genetic Diseases of the Kidneys
- 1001 Genetic Diseases of the Kidneys: Cystic
Authors
- Sekercioglu, Nigar, McMaster University, Hamilton, Ontario, Canada
- Fu, Rui, University of Toronto, Toronto, Ontario, Canada
- Lopes, Luciane C., Uniso, Sorocaba, Brazil
- Elias, Rosilene M., Universidade de Sao Paulo, Sao Paulo, Brazil
- Curtis, Bryan M., Memorial University, St. John's, Newfoundland, Canada
Group or Team Name
- ADPKD study
Background
ADPKD is the most common hereditary kidney disease with about 1:500 frequency, 100% penetrance and multisystem involvement. The purpose of this study is to explore the effectiveness and safety of disease-modifying agents for ADPKD.
Methods
We conducted searches on the MEDLINE, EMBASE and CINAHL databases from the inception to May 2019 for RCTs with ≥ six-month follow-up.Teams of two reviewers, independently and in duplicate, screened titles and abstracts, completed full-text reviews, and abstracted data. Eligible trials enrolled patients with ADPKD, randomized to receive rapamycin, everolimus, octreotide, tolvaptan, standard care, or placebo, and reported effects on patient-important outcomes (e.g., all-cause mortality), total kidney volume (TKV), glomerular filtration rate (GFR), or medication-related adverse events. We excluded preclinical experiments, crossover trials, and conference proceedings. We performed network meta-analysis (NMA) and pooled treatment effects as mean differences (MD) and calculated 95% credible intervals (Crls) using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence.
Results
Our search yielded 635 citations, of which 11 met the inclusion criteria and involved a total of 3703 adults with ADPKD, including 2106 (56%) patients receiving treatments and 1597 (44%) receiving placebo and/or standard care. The random-effects models suggested rapamycin leads to a reduced change of TKV at 12 months (NMA MD, -436 [95% Crl, -639 to -212]. Twenty-five comparisons failed to reach statistical significance in the network estimates for the GFR outcome. Patients treated with rapamycin at high target dose had a higher likelihood of slowing of GFR decline as compared to those treated with other treatment categories.
Conclusion
Our results suggest that rapamycin reduced changes in TKV at 12 months and in high doses attenuated the GFR decline.
Network meta-analysis results for GFR.
Forest plot of effectiveness outcome for mean GFR reduction at the end of the study period.