Pasireotide 10mg powder and solvent for suspension for injection vials

BackgroundPostpancreatectomy hemorrhage (PPH) is a leading cause for surgical mortality after pancreatic surgery. Several strategies for the prevention and management of PPH have been studied in randomized controlled trials (RCTs) but a systematic review is lacking. The authors systematically reviewed RCTs regarding the impact of treatment strategies on the incidence and outcome of PPH.Material and methodsEligible RCTs reporting on impact of treatment on the rate of PPH were identified through a systematic literature search using the Evidence Map of Pancreatic Surgery (2012-2022). Methodological quality was assessed using the Cochrane Risk of Bias 2 (RoB-2) tool for RCTs. Various definitions of PPH were accepted and outcome reported separately for the International Study Group for Pancreatic Surgery (ISGPS) definition.ResultsOverall, 99 RCTs fulfilled the eligibility criteria with a pooled 6.1% rate of PPH (range 1-32%). The pooled rate of PPH defined as ISGPS grade B/C was 8.1% (range 0-24.9%). Five RCTs reported five strategies that significantly reduced the rate of PPH. Three concerned surgical technique: pancreatic anastomosis with small jejunal incision, falciform ligament wrap around the gastroduodenal artery stump, and pancreaticojejunostomy (vs pancreaticogastrostomy). Two concerned perioperative management: perioperative pasireotide administration, and algorithm-based postoperative patient management. No single RCT specifically focused on the treatment of patients with PPH.ConclusionThis systematic review of RCTs identified five strategies which reduce the rate of PPH; three concerning intraoperative surgical technique and two concerning perioperative patient management. Future studies should focus on the treatment of patients with PPH as RCTs are currently lacking.

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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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BackgroundPost-bariatric hypoglycemia (PBH) is a challenging and increasingly recognized complication following bariatric surgery, particularly Roux-en-Y gastric bypass (RYGB). Multiple pharmacologic interventions have been explored for managing PBH, but evidence is scattered. This study aimed to systematically synthesize the evidence from comparative studies, single-intervention trials, case reports, and registered clinical trials to evaluate the efficacy of drug therapies for PBH.MethodsThis systematic review and mixed treatment comparison meta-analysis was conducted in accordance with PRISMA guidelines and registered on Open Science Framework. Databases searched included MEDLINE, Cochrane CENTRAL, and Google Scholar, with no language or year restrictions. Eligible studies included randomized clinical trials (RCTs), observational studies, single-drug evaluations, and case reports addressing pharmacologic treatments for PBH. Risk of bias was assessed using Cochrane and Joanna Briggs Institute tools. Mixed treatment comparisons were conducted with relative risk (RR) as effect estimates, and evidence quality was assessed with the GRADE approach.ResultsOut of 2134 records screened, 13 comparative studies, five single-intervention studies, and 15 case reports were included. Among comparative studies, 12 were RCTs and one was a retrospective study. Meta-analysis revealed that anakinra and empagliflozin significantly reduced the risk of hypoglycemia compared to placebo (RR: 0.29; 95% CI: 0.09-0.91 for both). Dasiglucagon showed efficacy as a rescue agent. In single-intervention studies, pasireotide and acarbose prevented hypoglycemia in all patients. Case reports suggested variable success with agents such as liraglutide, verapamil, and semaglutide. However, the certainty of evidence was rated very low, with small sample sizes, heterogeneous definitions of PBH, and imprecise effect estimates limiting the robustness of conclusions.ConclusionPharmacologic management of PBH shows promise with agents such as anakinra, empagliflozin, pasireotide, and acarbose. However, given the considerable heterogeneity, small sample sizes, and wide confidence intervals, very low quality of effect estimates, and varied definitions of PBH, these pooled estimates should be considered hypothesis-generating only, and not confirmatory. There is an urgent need for standardized PBH definitions, patient-centered outcome measures, longer follow-up, and adequately powered RCTs to establish evidence-based therapeutic guidelines.

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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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