Pansomatostatin Agonist Pasireotide Long-Acting Release for Patients with Autosomal Dominant Polycystic Kidney or Liver Disease with Severe Liver Involvement

Abstract

Background and objectivesWe assessed safety and efficacy of another somatostatin receptor analog, pasireotide long-acting release, in severe polycystic liver disease and autosomal dominant polycystic kidney disease. Pasireotide long-acting release, with its broader binding profile and higher affinity to known somatostatin receptors, has potential for greater efficacy.Design, setting, participants, & measurementsIndividuals with severe polycystic liver disease were assigned in a 2:1 ratio in a 1-year, double-blind, randomized trial to receive pasireotide long-acting release or placebo. Primary outcome was change in total liver volume; secondary outcomes were change in total kidney volume, eGFR, and quality of life.ResultsOf 48 subjects randomized, 41 completed total liver volume measurements (n=29 pasireotide long-acting release and n=12 placebo). From baseline, there were −99±189 ml/m absolute and −3%±7% change in annualized change in height-adjusted total liver volume (from 2582±1381 to 2479±1317 ml/m) in the pasireotide long-acting release group compared with 136±117 ml/m absolute and 6%±7% increase (from 2387±759 to 2533±770 ml/m) in placebo (P<0.001 for both). Total kidney volumes decreased by −12±34 ml/m and −1%±4% in pasireotide long-acting release compared with 21±21 ml/m and 4%±5% increase in the placebo group (P=0.05 for both). Changes in eGFR were similar between groups. Among the n=48 randomized, adverse events included hyperglycemia (26 of 33 [79%] in pasireotide long-acting release versus four of 15 [27%] in the placebo group; P<0.001), and among the 47 without diabetes at baseline, 19 of 32 (59%) in the pasireotide long-acting release group versus one of 15 (7%) in the placebo group developed diabetes (P=0.001).ConclusionsAnother somatostatin analog, pasireotide long-acting release, slowed progressive increase in both total liver volume/total kidney volume growth rates without affecting GFR decline. Participants experienced higher frequency of adverse events (hyperglycemia and diabetes).Clinical Trial registry name and registration numberPasireotide LAR in Severe Polycystic Liver Disease, NCT01670110PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_08_28_CJN13661119.mp3

Somatostatin analog therapy effectiveness on the progression of polycystic kidney and liver disease: A systematic review and meta-analysis of randomized clinical trials

“…A total of 10 RCTs that included a total of 854 patients were included in the qualitative and quantitative analysis [32][33][34][35][36][37][38][39][40][41]. We excluded the pooled study regarding LOCKCYST I TRIAL 1.…”

The effects of somatostatin analogues on liver volume and quality of life in polycystic liver disease: a meta-analysis of randomized controlled trials

“…After the screening of titles and abstracts carried out from search strategy, 21 studies out of 203 were considered potentially relevant. The full text of each of these articles was reviewed by two authors, and 6 eligible studies 6 , 16 – 20 , 22 were included in the meta-analysis (Fig. 1 ).…”

“…Three RCTs have evaluated Quality of life parameters measured by SF36 QOL questionnaire for a total of 124 patients evaluated (74 and 50 treated by SA and placebo/standard care respectively) 17 , 18 , 22 . As evidenced in Fig.…”

“…However, in this study some results were derived without an access to original data 21 . Furthermore, during the last year another RCT with a newer SA, pasireotide, was published 22 . On this basis, our meta-analysis aimed to investigate the real effects of SAs on liver volume, and it is the first work which explored the effects of SAs on QoL in PLD.…”

Current status and progress in the treatment of congenital liver cyst

“…It also has a good curative effect for patients with PLD and polycystic kidney disease. 33 More clinical data is needed for the research of somatostatin analogues. In addition to somatostatin analogues, mammalian target of rapamycin (mTOR), including sirolimus, everolimus and other drugs still lack sufficient clinical data to prove their effectiveness, and long-term use can increase infection and the incidence of malignant tumors.…”