Lanreotide Makes Its Mark in Tx of Rare Liver Disease

VIENNA -- Patients with polycystic kidney disease and polycystic liver disease randomized to treatment with lanreotide were associated with a reduction in liver volume compared to standard of care, a researcher said here.

Height-adjusted liver volume declined 1.99% (95% CI -4.21 to 0.24) in the lanreotide group compared to an increase of 3.92% with standard of care (95% CI 1.56-6.28), for a difference of -5.91% (95% CI -9.18 to -2.63, P<0.001), reported René van Aerts, MD, of Radboud University Medical Center in Nijmegen, the Netherlands.

van Aerts explained that polycystic liver disease is the most frequent extra-renal manifestation of autosomal dominant polycystic kidney disease (ADPKD) at a press conference at the European Association for the Study of the Liver (EASL) annual meeting.

"Polycystic kidney and liver disease patients will have renal cysts, but the majority also possess liver cysts ... and you can imagine this would cause substantial morbidity, because they develop symptoms like swollen bellies," he said.

Markus Peck-Radosavljevic, MD, of Klinikum Klagenfurt in Klagenfurt, Austria, who was not involved with the study, said that lanreotide, a somatostatin analogue, has been used before in the treatment of neuroendocrine tumors, because its mechanism of action is to decrease the production of fluid.

"You can cut a window into a cyst and drain liquid into the abdomen, but when you have multiple cysts, that's not an option," he told MedPage Today. "An alternative is a transplant, but that's quite a drastic treatment for someone with normal liver function."

The DIPAK-1 trial was a randomized 120-week open-label trial designed to examine the renoprotective effect of the treatment in patients with ADPKD. van Aerts' group examined a subset of patients who also had polycystic liver disease (defined as hepatic cysts on MRI and a liver volume ≥2,000 mL).

There were 305 DIPAK-1 trial participants ages 18-60, with ADPKD based on modified Ravine criteria and estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73m². Patients were randomized to lanreotide 120 mg subcutaneously once every 4 weeks or standard of care, which was defined as blood pressure reduction measures.

Of these participants, 175 met criteria for polycystic liver disease, 93 of which were randomized to lanreotide and 82 to standard of care. Primary endpoint was the percentage change in height-adjusted liver volume between baseline and end of treatment.

Peck-Radosavljevic said the reduction in the primary outcome was "not very strong," but noted that the control group showed an increase.

"If you can have a treatment with a decrease and that can block an increase, that could be meaningful. Potentially you could envision starting the treatment early and maybe prevent progression [of developing cysts]," he said.

van Aerts also noted improvements in the secondary endpoint, a change in height-adjusted liver and kidney volume for the lanreotide group versus standard of care (-7.18% difference, 95% CI -10.25 to -4.12, P<0.001). The authors also noted there was still a significant difference in height-adjusted liver volume in the two groups even 4 months after the end of treatment, and concluded that "treatment with somatostatin analogues should be considered in patients with enlarged liver and/or kidneys to prevent further disease progression."

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