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.
Octreotide and pasireotide may reduce total kidney volume in the short term, while lanreotide may show benefits over a longer period, but the clinical significance of these findings is unclear.
Where it sits
this study against the rest of the pasireotide corpusSummary and findings
This study 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 autosomal dominant polycystic kidney disease (ADPKD) or polycystic liver disease (PLD). Pooled estimates suggested that octreotide and pasireotide were associated with TKV reduction compared to placebo, while lanreotide showed a decrease in TKV after more than 2 years. Cholelithiasis was identified as the most common biliary adverse event across the three somatostatin analogs.
Abstract
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.
Background
This paper addresses the comparative efficacy and safety of somatostatin analogs in treating autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). Prior studies have indicated that these analogs may impact total kidney volume (TKV) and total liver volume (TLV), but direct comparisons among them are limited. Understanding the differences in efficacy and safety profiles is crucial for optimizing treatment strategies in these conditions.
Methods
The study utilized a network meta-analysis approach, incorporating real-world evidence from the FDA Adverse Event Reporting System (FAERS) database. The population included patients with ADPKD or PLD treated with octreotide, lanreotide, or pasireotide. The primary outcome measures were changes in TKV and TLV, assessed at various time points, including 6 months, 1 year, and more than 2 years.
Results
The primary endpoint showed that octreotide had a mean difference (MD) of -3.7 (95%CI: -4.3 to -3.2) at 6 months or 1 year, and pasireotide had an MD of -5.0 (95%CI: -8.2 to -1.8) at the same time frame. Lanreotide demonstrated a more significant reduction in TKV with an MD of -7.8 (95%CI: -10.2 to -5.4) after more than 2 years. TLV analyses indicated early directional effects for octreotide (-7.7, 95%CI: -12.1 to -3.3) and pasireotide (-9.0, 95%CI: -13.7 to -4.3) at 1 year.
Interpretation
The findings suggest that while all three somatostatin analogs have some efficacy in reducing TKV, lanreotide appears to show a more pronounced effect over a longer duration. However, the clinical significance of the observed reductions, particularly for pasireotide, may be limited given the modest effect sizes. Additionally, the reliance on real-world data introduces potential biases and confounding factors that could affect the conclusions drawn from this analysis.
Key findings
- MD: -3.7, 95%CI: -4.3 to -3.2 for octreotide at 6 months or 1 year.
- MD: -5.0, 95%CI: -8.2 to -1.8 for pasireotide at 6 months or 1 year.
- MD: -7.8, 95%CI: -10.2 to -5.4 for lanreotide after more than 2 years.
- MD: -7.7, 95%CI: -12.1 to -3.3 for octreotide at 1 year.
- HR: 0.966, 95% CI: 0.949 to 0.982, P < 0.001 for age as a predictor of cholelithiasis.
- HR: 2.168, 95% CI: 1.411 to 3.332, P < 0.001 for drug as a predictor of cholelithiasis.
Limitations
- Relies on pooled estimates from limited available trials.
- Uses real-world data from the FAERS database.
- Short follow-up periods for some outcomes.
- Potential confounding factors not fully addressed.