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The Cochrane Database of Systematic... Jun 2024Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Neovascular age-related macular degeneration (AMD) is a progressive eye disease characterized by choroidal neovascularization (CNV) and is a leading cause of vision loss and disability worldwide. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is an effective treatment option that helps to prevent vision loss or to improve visual acuity in people with neovascular AMD, treatment imposes a significant financial burden on patients and healthcare systems. A biosimilar is a biological product that has been developed to be nearly identical to a previously approved biological product. The use of biosimilars may help reduce costs and so may increase patient access to effective biologic medicines with similar levels of safety to the drugs on which they are based.
OBJECTIVES
To assess the benefits and harms of anti-VEGF biosimilar agents compared with their corresponding anti-VEGF agents (i.e. the reference products) that have obtained regulatory approval for intravitreal injections in people with neovascular AMD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registries together with reference checking and contact with study authors to identify studies that are included in the review. The latest search date was 2 June 2023.
ELIGIBILITY CRITERIA
We included randomized controlled trials (RCTs) that compared approved anti-VEGF biosimilars with their reference products for treating the eyes of adult participants (≥ 50 years) who had an active primary or recurrent choroidal neovascularization lesion secondary to neovascular AMD.
OUTCOMES
Our outcomes were: best-corrected visual acuity (BCVA), central subfield thickness (CST), vision-related quality of life, serious ocular and non-ocular adverse events (AE), treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADAs), and serum concentrations of biosimilars and reference drugs.
RISK OF BIAS
We assessed the risk of bias (RoB) for seven outcomes reported in a summary of findings table by using the Cochrane RoB 2 tool.
SYNTHESIS METHODS
We synthesized results for each outcome using meta-analysis, where possible, by calculating risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for dichotomous outcomes and continuous outcomes, respectively. Where this was not possible due to the nature of the data, we summarized the results narratively. We used GRADE to assess the certainty of evidence for prespecified outcomes.
INCLUDED STUDIES
We included nine parallel-group multi-center RCTs that enrolled a total of 3814 participants (3814 participating eyes), with sample sizes that ranged from 160 to 705 participants per study. The mean age of the participants in these studies ranged from 67 to 76 years, and the proportion of women ranged from 26.5% to 58.7%. Ranibizumab (Lucentis) was the reference product in seven studies, and aflibercept (Eyelea) was the reference product in two others. All the included studies had been supported by industry. The follow-up periods ranged from 12 to 52 weeks (median 48 weeks). Five studies (56%) were conducted in multi-country settings across Europe, North America and Asia, two studies in India, and one each in Japan and the Republic of Korea. We judged all the included studies to have met high methodological standards.
SYNTHESIS OF RESULTS
With regard to efficacy, our meta-analyses demonstrated that anti-VEGF biosimilars for neovascular AMD resulted in little to no difference compared with the reference products for BCVA change at 8 to 12 weeks (MD -0.55 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% CI -1.17 to 0.07; 8 studies, 3603 participants; high-certainty evidence) and the proportion of participants who lost fewer than 15 letters in BCVA at 24 to 48 weeks (RR 0.99, 95% CI 0.98 to 1.01; 7 studies, 2658 participants; moderate-certainty evidence). Almost all participants (96.6% in the biosimilar group and 97.0% in the reference product group) lost fewer than 15 letters in BCVA. The evidence from two studies suggested that there was no evidence of difference between biosimilars and reference products in vision-related quality of life measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) summary scores at 24 to 48 weeks (MD 0.82, 95% CI -0.70 to 2.35; 2 studies, 894 participants; moderate-certainty evidence). With regard to the safety profile, meta-analyses also revealed little to no difference between anti-VEGF biosimilars and the reference products for the proportion of participants who experienced serious ocular AEs (RR 1.24, 95% CI 0.68 to 2.26; 7 studies, 3292 participants; moderate-certainty evidence), and for TEAEs leading to investigational product discontinuation or death (RR 0.96, 95% CI 0.63 to 1.46; 8 studies, 3497 participants; moderate-certainty evidence). Overall, 1.4% of participants in the biosimilar group and 1.2% in the reference product group experienced serious ocular adverse events. The most frequently documented serious ocular AEs were retinal hemorrhage and endophthalmitis. Although the evidence is of low certainty due to imprecision, meta-analysis suggested that anti-VEGF biosimilars led to no difference compared with the reference products for cumulative incidence of ADAs (RR 0.84, 95% CI 0.58 to 1.22; 8 studies, 3066 participants; low-certainty evidence) or mean maximum serum concentrations (MD 0.42 ng/mL, 95% CI -0.22 to 1.05; subgroup of 3 studies, 100 participants; low-certainty evidence). We judged the overall risk of bias to be low for all studies.
AUTHORS' CONCLUSIONS
In our review, low to high certainty evidence suggests that there is little to no difference, to date, between the anti-VEGF biosimilars approved for treating neovascular AMD and their reference products in terms of benefits and harms. While anti-VEGF biosimilars may be a viable alternative to reference products, current evidence for their use is based on a limited number of studies - particularly for comparison with aflibercept - with sparse long-term safety data, and infrequent assessment of quality of life outcomes. Our effect estimates and conclusions may be modified once findings have been reported from studies that are currently ongoing, and studies of biosimilar agents that are currently in development.
FUNDING
Cochrane Eyes and Vision US Project is supported by grant UG1EY020522, National Eye Institute, National Institutes of Health. Takeshi Hasegawa and Hisashi Noma were supported by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (Grant numbers: 22H03554, 19K03092, 24K06239).
REGISTRATION
Protocol available via doi.org/10.1002/14651858.CD015804.
Topics: Aged; Humans; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Aptamers, Nucleotide; Bevacizumab; Bias; Biosimilar Pharmaceuticals; Choroidal Neovascularization; Intravitreal Injections; Macular Degeneration; Randomized Controlled Trials as Topic; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Vascular Endothelial Growth Factor A; Visual Acuity; Middle Aged; Male; Female
PubMed: 38829176
DOI: 10.1002/14651858.CD015804.pub2 -
Talanta Aug 2024Neonicotinoids, sometimes abbreviated as neonics, represent a class of neuro-active insecticides with chemical similarities to nicotine. Neonicotinoids are the most... (Review)
Review
Neonicotinoids, sometimes abbreviated as neonics, represent a class of neuro-active insecticides with chemical similarities to nicotine. Neonicotinoids are the most widely adopted group of insecticides globally since their discovery in the late 1980s. Their physiochemical properties surpass those of previously established insecticides, contributing to their popularity in various sectors such as agriculture and wood treatment. The environmental impact of neonicotinoids, often overlooked, underscores the urgency to develop tools for their detection and understanding of their behavior. Conventional methods for pesticide detection have limitations. Chromatographic techniques are sensitive but expensive, generate waste, and require complex sample preparation. Bioassays lack specificity and accuracy, making them suitable as preliminary tests in conjunction with instrumental methods. Aptamer-based biosensor is recognized as an advantageous tool for neonicotinoids detection due to its rapid response, user-friendly nature, cost-effectiveness, and suitability for on-site detection. This comprehensive review represents the inaugural in-depth analysis of advancements in aptamer-based biosensors targeting neonicotinoids such as imidacloprid, thiamethoxam, clothianidin, acetamiprid, thiacloprid, nitenpyram, and dinotefuran. Additionally, the review offers valuable insights into the critical challenges requiring prompt attention for the successful transition from research to practical field applications.
Topics: Insecticides; Aptamers, Nucleotide; Biosensing Techniques; Neonicotinoids; Guanidines; Thiamethoxam; Thiazoles; Nitro Compounds; Environmental Monitoring; Environmental Pollutants; Thiazines
PubMed: 38703483
DOI: 10.1016/j.talanta.2024.126190 -
Value in Health Regional Issues Jul 2024This study aims to systematically collect data on cost-effectiveness analyses that assess technologies to treat type I and II spinal muscular atrophy and evaluate their...
OBJECTIVES
This study aims to systematically collect data on cost-effectiveness analyses that assess technologies to treat type I and II spinal muscular atrophy and evaluate their recommendations.
METHODS
A structured electronic search was conducted in 4 databases. Additionally, a complementary manual search was conducted. Complete economic studies that evaluated nusinersen, risdiplam, onasemnogene abeparvovec (OA), and the best support therapy (BST) from the health system's perspective were selected. The incremental cost-effectiveness ratios were compared with various thresholds for the analysis. The review was registered a priori in PROSPERO (CRD42022365391).
RESULTS
Twenty studies were included in the analyses. They were all published between 2017 and 2022 and represent the recommendations in 8 countries. Most studies adopted 5, 6, or 10-state Markov models. Some authors took part in multiple studies. Four technologies were evaluated: BST (N = 14), nusinersen (N = 19), risdiplam (N = 5), and OA (N = 9). OA, risdiplam, and nusinersen were considered inefficient compared with the BST. Risdiplam and OA were generally regarded as cost-effective when compared with nusinersen. Because nusinersen is not a cost-effective drug, no recommendation can be derived from this result. Risdiplam and OA were compared in 2 studies that presented opposite results.
CONCLUSIONS
Nusinersen, risdiplam, and OA are being adopted worldwide as a treatment for spinal muscular atrophy. Despite that, the pharmacoeconomic analyses show that the technologies are not cost-effective compared with the BST. The lack of controlled studies for risdiplam and OA hamper any conclusions about their face-to-face comparison.
Topics: Humans; Cost-Benefit Analysis; Muscular Atrophy, Spinal; Oligonucleotides; Aptamers, Nucleotide; Azo Compounds; Pyrimidines
PubMed: 38669792
DOI: 10.1016/j.vhri.2024.02.002 -
International Journal of Antimicrobial... Mar 2024Peptide nucleic acids (PNAs) are synthetic molecules that are like DNA/RNA, but with different building blocks. PNAs target and bind to mRNAs and disrupt the function of... (Review)
Review
Peptide nucleic acids (PNAs) are synthetic molecules that are like DNA/RNA, but with different building blocks. PNAs target and bind to mRNAs and disrupt the function of a targeted gene, hence they have been studied as potential antibacterials. The aim of this systematic review was to provide an in-depth analysis of the current status of PNAs as antibacterial agents, define the characteristics of the effective PNA constructs, and address the gap in advancing PNAs to become clinically competent agents. Following the PRISMA model, four electronic databases were searched: Web of Science, PubMed, SciFinder and Scopus. A total of 627 articles published between 1994 and 2023 were found. After screening and a rigorous selection process using explicit inclusion and exclusion criteria, 65 scientific articles were selected, containing 656 minimum inhibitory concentration (MIC) data. The antibacterial activity of PNAs was assessed against 20 bacterial species. The most studied Gram-negative and Gram-positive bacteria were Escherichia coli (n=266) and Staphylococcus aureus (n=53), respectively. In addition, the effect of PNA design, including construct length, binding location, and carrier agents, on antibacterial activity was shown. Finally, antibacterial test models to assess the inhibitory effects of PNAs were examined, emphasising gaps and prospects. This systematic review provides a comprehensive assessment of the potential of PNAs as antibacterial agents and offers valuable insights for researchers and clinicians seeking novel therapeutic strategies in the context of increasing rates of antibiotic-resistant bacteria.
Topics: Anti-Bacterial Agents; Bacteria; Peptide Nucleic Acids; Staphylococcus aureus
PubMed: 38185398
DOI: 10.1016/j.ijantimicag.2024.107083