Comparative Efficacy and Safety of Octreotide, Lanreotide, and Pasireotide in ADPKD and PLD: A Network Meta-analysis with Real-world Evidence from the FAERS Database

Somatostatin analogs were the primary treatment for autosomal dominant polycystic kidney disease (ADPKD) or polycystic liver disease (PLD), including octreotide, lanreotide, and pasireotide. We compared the effects and safety of octreotide, lanreotide, and pasireotide on total kidney volume (TKV), total liver volume (TLV), and kidney function (eGFR) in patients with ADPKD or PLD using network meta-analysis and FDA Adverse Event Reporting System (FAERS) data. Pooled estimates from limited available trials suggested that, at 6 months or 1 year, octreotide (MD: -3.7, 95%CI: -4.3 to -3.2) and pasireotide (-5.0, -8.2 to -1.8) were associated with preliminary evidence of TKV reduction compared with placebo. However, lanreotide (-7.8, -10.2 to -5.4) obviously manifested a decrease in the TKV after more than 2 years. TLV analyses showed early directional effects of octreotide (-7.7, -12.1 to -3.3) and pasireotide (-9.0, -13.7 to -4.3) at 1 year, and for lanreotide (-5.0, -6.3 to -3.9) after more than 2 years. Lanreotide demonstrated inferior efficacy in reducing the TLV growth rate compared to octreotide (10.0, 2.7 to 18.0) following a 2-3 year administration period. Cholelithiasis is the most common biliary adverse event in three somatostatin analogs. Cox regression identified age (HR: 0.966, 95% CI: 0.949 to 0.982, P < 0.001) and drug (HR: 2.168, 95% CI: 1.411 to 3.332, P < 0.001) as independent predictors of cholelithiasis. The onset time of TKV/TLV reduction differs among the three somatostatin analogs. Age and drug were independent predictors of cholelithiasis. Younger patients or those receiving pasireotide are at higher risk of cholelithiasis.