Pegvisomant 20mg powder and solvent for solution for injection vials

BackgroundPasireotide long-acting release (PasiLAR), a somatostatin multireceptor ligand, is effective in achieving biochemical control but can increase the risk of hyperglycemia in acromegaly. However, the impact of PasiLAR on lipid and glucose metabolism in patients with acromegaly has not been systematically studied. This systematic review aimed at synthesizing evidence on PasiLAR effects (as monotherapy or combination therapy with pegvisomant) on lipid and glucose metabolism in patients with acromegaly.MethodsMEDLINE, Embase, Cochrane Library, and Web of Science were searched for studies published between 2000 and 2024. Prospective and retrospective studies reporting metabolic outcomes before and under PasiLAR treatment for a minimum follow-up of 6 months. Two reviewers screened eligible publications (3441), extracted outcomes, and assessed risk of bias.ResultsNineteen studies (896 patients) were included in the meta-analysis. PasiLAR was associated with increased fasting plasma glucose (FPG) (mean difference [MD] 23.4 mg/dL, 95% confidence interval [95%CI] 18.8-28.1]) and glycated hemoglobin (HbA1c) (MD 0.5%, 95%CI 0.4-0.7). A higher frequency of diabetes mellitus (DM) was observed after treatment (odds ratio 3.7, 95%CI 2.9-4.7). No significant changes in triglycerides, total cholesterol, or low-density lipoprotein cholesterol (LDL-C), and a modest but significant increase in high-density lipoprotein cholesterol (HDL-C) were recorded (MD 6.2 mg/dL, 95%CI 1.4-10.9]).ConclusionsIn this large meta-analysis, PasiLAR was associated with increased HDL-C, FPG, HbA1c, and frequency of DM in patients with acromegaly. There was no effect on triglycerides, total cholesterol, and LDL-C.Prospero registration numberCRD42024544686.

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ObjectiveAcromegaly is a rare disorder caused by a growth hormone-secreting pituitary adenoma. Clinical trial evidence for its management is limited. This study compared medical treatments for acromegaly through a network meta-analysis, assessing biochemical and radiological responses.DesignA systematic review and network meta-analysis were conducted following the preferred reporting items for systematic reviews and network meta-analyses guidelines and Cochrane Handbook recommendations (PROSPERO registration: CRD42023364373).MethodsPubMed, Scopus, and Web of Science were searched up to June 2024. Included studies were randomized controlled trials and nonrandomized studies evaluating the efficacy or safety of acromegaly treatments. Primary outcomes were the percentage of adjusted insulin-like growth factor 1 (IGF-1) normalization and tumor shrinkage.ResultsTwenty-seven studies, involving 4131 patients and 11 treatments were included. Pegvisomant was the best treatment for IGF-1 normalization, followed by pasireotide LAR. Both outperformed first-generation somatostatin receptor ligands (SRLs) combined with dopamine agonists (odds ratio [OR], 1.83; 95% CIs, 1.37-2.46 and OR, 1.46; 95% CIs, 1.02-2.08, respectively; I2 = 41%). Octreotide LAR was superior to oral octreotide capsules (OR, 5.41; 95% CIs, 1.89-15.52). For tumor shrinkage, pasireotide LAR was more effective than SRLs (n = 1059; OR, 11.47; 95% CIs, 1.5-87.64; I2 = 0%). Methodological heterogeneity may have affected comparability.ConclusionsOur findings suggest pasireotide LAR and pegvisomant as the most effective treatments for IGF-1 normalization. Pasireotide LAR was the best treatment for tumor shrinkage, though the evidence base was limited, requiring cautious interpretation. Their potential role as first-line options after surgery requires further research. Clinical decisions should consider cost, safety, and patient-specific parameters to optimize outcomes.

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ContextThere are limited head-to-head trials comparing pharmacological treatments for acromegaly.ObjectiveSystematically review the efficacy and safety of pharmacological treatments for acromegaly and conduct a network meta-analysis (NMA) enabling indirect comparisons.MethodsMEDLINE 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.ResultsTwenty-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.ConclusionThis 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.

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ObjectiveThis updated French cost-utility analysis aimed to assess the efficacy of the second-line pharmacological treatment - pegvisomant, pasireotide or pegvisomant combined with first generation somatostatin analogues (FGSA) - considering first-line treatment (surgery, FGSA, cabergoline and combination), radiotherapy and the impact of treatment on tumor volume.MethodsThe original three-state Markov model was revised to include an additional health state, representing patients controlled without pharmacological treatment following successful radiotherapy. The model also accounted for the history of first-line treatments as additional costs upon patients' entry. A cohort of 1000 simulated patients was followed over a lifetime horizon from a collective perspective. Treatment efficacy is defined on normalization of insulin growth factor-1 and was determined through a network meta-analysis. Cost and utility data were sourced from French databases and literature.ResultsAll the evaluated treatments were included in an efficiency frontier. The incremental cost-utility ratio (ICUR) of pegvisomant compared to pasireotide was 27,805€ per quality-adjusted life year (QALY) gained. The ICUR of pegvisomant combined with FGSA compared to pegvisomant was 253,854€/QALY. Sensitivity analyses showed the robustness of the results. The addition of radiotherapy has shown improved quality of life and lower costs for all second-line treatments.ConclusionThis model explores the cost-effectiveness of second-line pharmacological treatments of acromegaly accounting for the overall management recommended in France. Radiotherapy appears as a key therapeutic option allowing long-term remission of patients even after pharmacological treatment failure. This study is an additional tool for treatment choice including both a clinical and economic perspective.Significance statementThe aim of this study is to assess the cost-utility of second-line treatments of acromegaly accounting for the overall management recommended in France, considering surgery, first-line treatments, radiotherapy and the impact of treatments on tumor volume, in addition to IGF-1 normalization. All evaluated treatments were included in an efficiency frontier. This addition has shown that radiotherapy and the impact on tumor volume are decisive in the management of second-line treatments for acromegaly. Indeed, radiotherapy enables patients to achieve complete remission, i.e. without the need for drug treatment. This is an important factor for patients, given that acromegaly treatments are chronic and usually lifelong. This study is an additional tool for treatment choice including both a clinical and economic perspective.

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