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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BackgroundAcromegaly is a rare, chronic disease caused by excessive growth hormone (GH) production due to pituitary adenoma. The disease severely impacts patients' health-related quality of life and mortality while imposing a substantial economic burden. Resistance to first-line medical treatment necessitates effective second-line therapies, including pasireotide long-acting release (PAS LAR) and pegvisomant (PEG).ObjectiveTo evaluate the cost-effectiveness of PAS LAR versus PEG (monotherapy or combined with FGSRLs) and versus FGSRLs alone, as second-line medical treatments for adults with acromegaly who are not adequately controlled on FGSRLs, from the perspective of the Brazilian Unified Health System (SUS).MethodsA hybrid decision-tree and Markov model were developed to evaluate lifetime health and economic outcomes of assessed drugs. To inform the model, health outcomes data were sourced from clinical trials, real-world evidence, systematic reviews, and meta-analyses. Costs were extracted from the official Brazilian tariffs database. Comparators included the FGSRLs, lanreotide (LAN) and octreotide (OCT), and PEG, as monotherapy and in combination with FGSRLs. Deterministic and probabilistic sensitivity analysis were performed to assess the impact of uncertainty on results. The incremental cost-effectiveness ratio (ICER) was the primary analysis outcome.ResultsPAS LAR was dominant versus PEG monotherapy and in combination with LAN, generating similar health benefits (an additional 0.17 and 0.10 QALYs, respectively) and lower therapy costs (savings of -R$538,945 [-US$100,675] and -R$782,542 [-US$146,179]). In the comparison with PEG combined with OCT, PAS LAR was less costly (-R$979,624 [-US$182,994]) and marginally less effective (-0.04 QALYs). Compared to FGSRLs, PAS LAR demonstrated improved health outcomes (QALYs) and increased cost. The ICERs were R$161,411 (US$30,152)/QALY and R$168,538 (US$31,483)/QALY versus OCT and LAN, respectively. Scenario analyses confirmed robustness across variations in key model inputs that have the highest impact on cost-effectiveness results.ConclusionsThe findings showed that in the Brazilian SUS context, PAS LAR is cost-effective compared to PEG monotherapy and PEG + LAN, and cost-saving versus PEG + OCT. Compared to FGSRLs, PAS LAR provided better outcomes with higher costs. With limited options for second-line medical treatment in Brazil, the reimbursement of PAS LAR in acromegaly can be considered a cost-effective strategy for acromegaly patients.

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