Bevacizumab gamma 7.5mg/0.3ml solution for injection vials

BACKGROUND: Insulin autoimmune syndrome (IAS) is a rare immune-mediated hypoglycemic disorder predominantly triggered by pharmacological agents. Despite the established links to thiol-containing drugs, emerging non-thiol triggers and significant geographical reporting biases limit comprehensive risk profiling. This study integrated pharmacovigilance data and published evidence to establish the first systematic epidemiological and pharmacological profile of drug-induced IAS. METHODS: We analysed 228 IAS cases from the FDA AE Reporting System (FAERS; 2004-Q2 2024) and a systematic review of 263 published cases (1980-2024). Multimodal disproportionality analysis-including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN)-identified drug-induced adverse event signals. Associations were stratified into a three-tier evidence framework (Levels 1-3) based on methodological concordance, case counts, and strength of the supporting literature. RESULTS: Fifty-eight agents showed potential IAS associations, including 12 novel pharmacovigilance signals (e.g., bevacizumab, sitagliptin, amlodipine, and olmesartan). Thiol-containing drugs exhibit the strongest signals (PRR > 200; e.g., captopril, methimazole, and clopidogrel). Level 1 evidence (highest confidence) implicated the use of clopidogrel, captopril, omeprazole, and methimazole. IAS was predominantly affected in older patients (median age, 66 years; IQR, 58-77 years), with a male predominance (59.21%), reflecting sex-specific prescription patterns. Geographical disparities persisted, with 85.17% of the cases reported in the literature in Asia. Reports of hypoglycemia exceeded IAS cases for most agents, suggesting an underdiagnosis. CONCLUSIONS: This study established the first evidence-based hierarchy for drug-induced IAS, identifying 58 agents warranting clinical vigilance. Thiol-containing drugs dominate the high-risk profile; however, novel associations (e.g., proton pump inhibitors (PPIs), dipeptidyl peptidase-4 (DPP-4) inhibitors) reveal broader immunological mechanisms. Clinicians should prioritize IAS in older patients with unexplained hypoglycemia exposed to antiplatelet agents or PPIs. Standardized diagnostic criteria and pharmacogenetic profiling (e.g., human leukocyte antigen DRB1 (HLA-DRB1) *04:06) are urgently required to improve detection.

Abstract licence: CC BY-NC-ND

This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments.

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Gamma Knife Radiosurgery (GKRS) is now an established standard of treatment for the small-sized arteriovenous malformations (AVMs), meningiomas, schwannomas, metastasis, and other benign diseases. With an exponential rise in the indications for GKRS, we have witnessed an increase in the adverse radiation effects (ARE) following GKRS. The common AREs and associated risk factors following GKRS have been described for pathologies including vestibular schwannomas, arteriovenous malformations, meningiomas, and metastases based on the authors' experience, and a simplified management protocol has been provided for radiation-induced changes based on clinical and radiologic parameters. The dose, volume, location, and repeat stereotactic radiosurgery (SRS) are implied as the risk factors for ARE. Clinically symptomatic AREs require oral steroids for weeks to alleviate symptoms. In refractory cases, bevacizumab and surgical resection can be offered as a treatment modality. Appropriate dose planning strategy and hypofractionation for larger lesions help in mitigating the AREs.

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INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

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Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

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Aim: This study aimed to evaluate the ability of a previously reported tumor marker (TM) score involving alpha-fetoprotein (AFP), fucosylated AFP (AFP-L3), and des gamma-carboxy prothrombin (DCP) as TMs in predicting the prognosis and therapeutic efficacy in hepatocellular carcinoma (HCC) patients administered atezolizumab plus bevacizumab (Atez/Bev) as first-line treatment. Materials/Methods: The study period covered September 2020 to December 2022 and involved 371 HCC patients treated with Atez/Bev. The values of the TMs AFP, AFP-L3, and DCP were measured upon introducing Atez/Bev. Elevations in the values of AFP (≥100 ng/mL), AFP-L3 (≥10%), and DCP (≥100 mAU/mL) were considered to indicate a positive TM. The number of positive TMs was summed up and used as the TM score, as previously proposed. Hepatic reserve function was assessed using the modified albumin–bilirubin grade (mALBI). Predictive values for prognosis were evaluated retrospectively. Results: A TM score of 0 was shown in 81 HCC patients (21.8%), 1 in 110 (29.6%), 2 in 112 (29.9%), and 3 in 68 (18.3%). The median overall survival (OS) times for TM scores 0, 1, 2, and 3 were not applicable [NA] (95% CI NA-NA), 24.0 months (95% CI 17.8-NA), 16.7 months (95% CI 17.8-NA), and NA (95% CI 8.3-NA), respectively (p < 0.001). The median progression-free survival (PFS) times for TM scores 0, 1, 2, and 3 were 16.5 months (95% CI 8.0-not applicable [NA]), 13.8 months (95% CI 10.6–21.3), 7.7 months (95% CI 5.3–8.9), and 5.8 months (95% CI 3.0–7.6), respectively (p < 0.001). OS was well stratified in mALBI 1/2a and mALBI 2a/2b. PFS was well stratified in mALBI 2a/2b, but not in mALBI 1/2a. Conclusions: The TM score involving AFP, AFP-L3, and DCP as TMs was useful in predicting the prognosis and therapeutic efficacy in terms of OS and PFS in HCC patients administered Atez/Bev as first-line treatment.

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