Efficacy of 4 Years of Octreotide Long-Acting Release Therapy in Patients With Severe Polycystic Liver Disease

Abstract

Objective: To observe the effect on total liver volume (TLV) on and off therapy in selected symptomatic patients with autosomal dominant polycystic kidney disease (ADPKD) or autosomal dominant polycystic liver disease (PLD) who received octreotide long-acting release (OctLAR) for up to 4 years.

Patients and methods: Twenty-eight of 42 participants in a prospective 2-year clinical trial of OctLAR (40 mg monthly) consisting of double-blind, randomized (year 1) and open-label treatment (year 2) phases reenrolled in a 2-year open-label extension (OLE) study after being off OctLAR a mean of 8.3 months (original study: July 1, 2007, through June 30, 2013). Participants underwent magnetic resonance imaging at baseline, years 1 and 2, reenrollment, and study completion. Primary end point: change in TLV; secondary end points: changes in total kidney volume, glomerular filtration rate, quality of life (QoL), safety, vital signs, and laboratory parameters.

Results: Twenty-five participants (59.5%) completed the OLE. Off therapy, TLVs increased a mean ± SD of 3.4%±8.2% per year; after resuming therapy, TLVs decreased a mean ± SD of -4.7%±6.1% per year. Despite regrowth off treatment, overall reductions were observed, with a median (interquartile range) TLV of 4047 mL (3107-7402 mL) at baseline and 3477 (2653-7131 mL) at study completion (-13.2%; P<.001) and with improved health-related QoL. Total kidney volumes increased, and glomerular filtration rates declined from 58.2 mL/min to 54.5 mL/min (n=16) in patients with ADPKD on therapy from baseline to study completion.

Conclusion: Therapy with OctLAR over 4 years in selected patients with symptomatic PLD arrested PLD progression, alleviating symptoms and improving health-related QoL. Discontinuation led to organ regrowth.

Trial registration: clinicaltrials.gov Identifier: NCT00426153.

FIGURE 1

Study flowchart. CKD5 = chronic kidney disease stage 5; OctLAR = octreotide long-acting release.

FIGURE 2

A, The original octreotide long-acting release (OctLAR) and placebo groups experienced increases in total liver volume (TLV) while off OctLAR from year 2 to reenrollment in a 2-year open-label extension study (OLE_baseline). B, The original OctLAR and placebo groups showed reductions in TLV while on OctLAR during the 2 years from OLE_baseline to open-label extension study completion (OctLAR n=1, placebo n=8). The boxes extend from the 25th to the 75th percentile and are bisected by the median; the whiskers extend to the most extreme value within 1.5 of the interquartile range; values beyond that and the mean are denoted by symbols. These data are censored for patients who underwent cyst aspiration.

FIGURE 3

Comparison of serial coronal liver magnetic resonance imaging studies in three participants, including additional liver volume data after their 2-year open-label extension period. Adapted from Nephrol Dial Transplant, with permission.