Somatostatin analog therapy for severe polycystic liver disease: results after 2 years

Abstract

Background: We showed in a randomized double-blinded placebo-controlled clinical trial that octreotide long-acting repeatable depot.® (OctLAR(®)) for 12 months reduces kidney and liver growth in autosomal dominant polycystic kidney patients with severe polycystic liver disease (PLD) and liver growth in patients with severe isolated PLD. We have now completed an open-label extension for one additional year to assess safety and clinical benefits of continued use of OctLAR for 2 years (O → O) and examined drug effect in the placebo group who crossed over to OctLAR in Year 2 (P → O).

Methods: The primary end point was change in total liver volume (TLV) measured by magnetic resonance imaging (MRI); secondary end points were changes in total kidney volume (TKV) measured by MRI, glomerular filtration rate (GFR), quality of life (QOL), safety, vital signs and laboratory parameters.

Results: Forty-one of 42 patients received OctLAR (n = 28) or placebo (n = 14) in Year 1 and received OctLAR in Year 2 (maximum dose 40 mg). Patients originally randomized to placebo (P → O) showed substantial reduction in TLV after treatment with OctLAR in Year 2 (Δ% -7.66 ± 9.69%, P = 0.011). The initial reduction of TLV in the OctLAR group (O → O) was maintained for 2 years (Δ% -5.96 ± 8.90%), although did not change significantly during Year 2 (Δ% -0.77 ± 6.82%). OctLAR inhibited renal enlargement during Year 1 (Δ% +0.42 ± 7.61%) in the (O → O) group and during Year 2 (Δ% -0.41 ± 9.45%) in the (P → O) group, but not throughout Year 2 (Δ% +6.49 ± 7.08%) in the (O → O) group. Using pooled analyses of all individuals who received OctLAR for 12 months, i.e. in Year 1 for O → O patients and Year 2 for P → O patients, average reduction in TLV was -6.08 ± 7.58% (P = 0.001) compared to net growth of 0.9 ± 8.35% in the original placebo group. OctLAR-treated individuals continued to experience improvements in QOL in Year 2, although overall physical and mental improvements were not significant during Year 2 compared to Year 1. Changes in GFR were similar in both groups.

Conclusion: Over 2 years, OctLAR significantly reduced the rate of increase in TLV and possibly the rate of increase in TKV.

Figures

Fig. 1.

Study flow diagram: 41 patients were enrolled in the second year (open-label extension). One individual withdrew voluntarily due to steatorrhea associated with OctLAR after completing the first year.

Fig. 2.

Effects of OctLAR therapy on the TLV and TKVs as represented by percentage changes (mean ± SD) during Year 1 (from baseline to Month 12) and Year 2 (mean ± SD) (from Month 12 to Month 24). (A) Percentage change in TLV (mL) (mean ± SD) in patients who received placebo (P) for 1 year and then crossed over to OctLAR during Year 2 (O) (P→O) or receiving continuous OctLAR treatment for 2 years (O→O). *P = 0.011 compared to TLV assessed by the end of Year 1; **P = 0.002 compared to baseline. (B) Percentage change (mean ± SD) in TKV on placebo and then crossed over to OctLAR during Year 2 (P→O) or receiving continuous OctLAR treatment for 2 years (O→O). *P = 0.05 compared to baseline; **P = 0.008 compared to TKV assessed by the end of 1 year.

Fig. 3.

Reduction of liver cyst burden in patients receiving continuous OctLAR therapy. Representative serial coronal abdominal and pelvic MRI views of three participants who underwent OctLAR therapy for 2 years. The images are standardized to visualize interval change in large cysts attributable to OctLAR therapy. Patient 1 had a decrease of 25%, Patient 2 of 10% and Patient 3 of 13% in TLV.