Efficacy and safety of pharmacologic therapies in acromegaly: a systematic literature review and network meta-analysis.

CONTEXT: There are limited head-to-head trials comparing pharmacological treatments for acromegaly.

OBJECTIVE

Systematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons.

METHODS

MEDLINE and Embase were searched to identify randomized controlled trials (RCTs) of acromegaly therapies. Screening and data extraction followed PRISMA guidelines. Feasibility assessment evaluated homogeneity and consistency assumptions required for NMA. Bayesian NMAs estimated relative treatment effects and ranking probabilities.

RESULTS

Twenty-two records covering 18 RCTs were included. Biochemical control rates were comparable among long-acting injectable somatostatin receptor ligands (SRLs), including lanreotide autogel (LAN-ATG), octreotide long-acting release (OCT-LAR), pasireotide, the GH receptor antagonist pegvisomant, oral octreotide (O-OCT), octreotide subcutaneous depot (SC-OCT-D), and the once-daily oral SRL paltusotine. Paltusotine demonstrated significantly higher biochemical control vs O-OCT and SC-OCT-D (odds ratios [ORs], 95% credible intervals [CrIs]: 7.34 [1.48-36.07] and 7.85 [1.72, 36.25]). Pasireotide showed significantly higher biochemical control vs OCT-LAR (OR: 2.03 [1.29-3.23]). Paltusotine had significantly lower discontinuations due to adverse events (AEs) vs O-OCT and SC-OCT-D, (ORs: 0.022 [0.001-0.424] and 0.022 [0.001-0.343]), with similar rates to other treatments. Treatment-emergent AEs (TEAEs) and serious TEAEs were comparable across treatments. Rankings suggested paltusotine as the treatment with the highest probability of ranking as the most effective (or tolerable) treatment across all endpoints studied.

CONCLUSION

This systematic review and NMA consolidate recent high-quality RCT evidence for acromegaly treatments. Paltusotine emerges as a promising alternative to injectable SRLs, with favorable efficacy, safety, and AE-related discontinuation patterns. These findings may inform clinical decision-making and guideline development, if confirmed by clinical experience.