Pasireotide 900micrograms/1ml solution for injection ampoules

Pasireotide long-acting release (PAS-LAR) is a second-generation somatostatin receptor ligand (SRL) approved for acromegaly treatment. This meta-analysis aimed to evaluate the real-world effectiveness and safety of PAS-LAR in patients with acromegaly resistant to first-generation somatostatin receptor ligands (fgSRL). A systematic literature search was conducted in PubMed and Web of Science for real-world studies on PAS-LAR in acromegaly published between 2014 and 2023. Random-effects meta-analyses were performed on biochemical control rates, tumor shrinkage, and metabolic parameters. Twelve studies comprising 409 patients were included. The pooled rate of insulin-like growth factor 1 (IGF-1) control was 57.9% [95% CI: 48.4–66.8] and the percentage of patients with tumor shrinkage was 33.3% [95%CI: 19.7–50.4]. Significant reductions were observed in growth hormone standardized mean difference (SMD) 0.6 ng/mL [95% CI: 0.3 to 1.0] and IGF-1 levels SMD 0.9 ULN [95% CI: 0.4 to 1.4]. However, as expected, a worsening in glucose metabolism was noted as an increase in fasting glucose SMD − 0.8 mg/dL [95% CI: -1.0 to -0.5, p < 0.01], glycated hemoglobin SMD − 0.5% [95% CI: -0.7 to -0.2]. and type 2 diabetes mellitus prevalence SMD − 11.5% (95% CI: -17.5 to -5.5). PAS-LAR demonstrated higher effectiveness in real-world settings, with over 60% of patients achieving IGF-1 control compared to the around 30% efficacy observed in clinical trials. These findings suggest that PAS-LAR is an effective option for acromegaly patients resistant to fgSRL, but careful monitoring of glucose levels is essential. The high heterogeneity observed across studies emphasizes the need for identifying PAS-LAR response biomarkers to set-up individualized treatment approaches for optimizing patient outcomes.

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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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Pasireotide 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. MEDLINE, 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. Nineteen 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]). In 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. CRD42024544686.

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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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