Lanreotide Reduces Liver Growth In Patients With Autosomal Dominant Polycystic Liver and Kidney Disease

Gastroenterology. 2019 Aug;157(2):481-491.e7. doi: 10.1053/j.gastro.2019.04.018. Epub 2019 Apr 22.

Abstract

Background & aims: Polycystic liver disease is the most common extrarenal manifestation of autosomal dominant polycystic kidney disease (ADPKD). There is need for robust long-term evidence for the volume-reducing effect of somatostatin analogues. We made use of data from an open-label, randomized trial to determine the effects of lanreotide on height-adjusted liver volume (hTLV) and combined height-adjusted liver and kidney volume (hTLKV) in patients with ADPKD.

Methods: We performed a 120-week study comparing the reno-protective effects of lanreotide vs standard care in 305 patients with ADPKD (the DIPAK-1 study). For this analysis, we studied the 175 patients with polycystic liver disease with hepatic cysts identified by magnetic resonance imaging and liver volume ≥2000 mL. Of these, 93 patients were assigned to a group that received lanreotide (120 mg subcutaneously every 4 weeks) and 82 to a group that received standard care (blood pressure control, a sodium-restricted diet, and antihypertensive agents). The primary endpoint was percent change in hTLV between baseline and end of treatment (week 120). A secondary endpoint was change in hTLKV.

Results: At 120 weeks, hTLV decreased by 1.99% in the lanreotide group (95% confidence interval [CI], -4.21 to 0.24) and increased by 3.92% in the control group (95% CI, 1.56-6.28). Compared with the control group, lanreotide reduced the growth of hTLV by 5.91% (95% CI, -9.18 to -2.63; P < .001). Growth of hTLV was still reduced by 3.87% at 4 months after the last injection of lanreotide compared with baseline (95% CI, -7.55 to -0.18; P = .04). Lanreotide reduced growth of hTLKV by 7.18% compared with the control group (95% CI, -10.25 to -4.12; P < .001).

Conclusions: In this subanalysis of a randomized trial of patients with polycystic liver disease due to ADPKD, lanreotide for 120 weeks reduced the growth of liver and combined liver and kidney volume. This effect was still present 4 months after the last injection of lanreotide. ClinicalTrials.gov, Number: NCT01616927.

Keywords: Drug; Liver Size; Polycystic Liver Disease; Somatostatin Analogues.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cysts / diagnostic imaging
  • Cysts / drug therapy*
  • Cysts / etiology
  • Cysts / pathology
  • Drug Administration Schedule
  • Female
  • Humans
  • Injections, Subcutaneous
  • Kidney / diagnostic imaging
  • Kidney / drug effects
  • Kidney / pathology*
  • Liver / diagnostic imaging
  • Liver / drug effects
  • Liver / pathology*
  • Liver Diseases / diagnostic imaging
  • Liver Diseases / drug therapy*
  • Liver Diseases / etiology
  • Liver Diseases / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Organ Size / drug effects
  • Peptides, Cyclic / administration & dosage*
  • Polycystic Kidney, Autosomal Dominant / complications
  • Polycystic Kidney, Autosomal Dominant / diagnostic imaging
  • Polycystic Kidney, Autosomal Dominant / drug therapy*
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives*
  • Treatment Outcome

Substances

  • Peptides, Cyclic
  • lanreotide
  • Somatostatin

Associated data

  • ClinicalTrials.gov/NCT01616927