Safety of daratumumab in the real-world: a pharmacovigilance study based on FAERS database.

BACKGROUND: Daratumumab is widely used in multiple myeloma (MM) and light chain amyloidosis (AL amyloidosis). The purpose of this study was to identify adverse event (AE) signals for daratumumab through the FDA Adverse Event Reporting System (FAERS) database to assess its safety in a large sample of people. METHODS: Based on data from the FAERS database, three disproportionality analysis methods were used to mine AE signals for daratumumab, including reporting odd ratio (ROR), proportional reporting ratio (PRR), and bayesian configuration promotion neural network (BCPNN). RESULTS: A total of 9220 AE reports with daratumumab as the primary suspect drug were collected, containing 23,946 AEs. Within these reports, 252 preferred terms (PT) levels, 73 high level term (HLT) levels and 11 system organ class (SOC) levels of AE signals were detected, along with some new AEs. Most AEs occurred within the first month after drug administration. CONCLUSION: Our findings were consistent with the results of established studies that daratumumab has a good safety profile. The newly identified AEs are of concern and prospective clinical studies are needed to confirm whether they are causally related to daratumumab. This study provided an early warning for the safe use of daratumumab and also provided guidance for further safety studies.

A multicenter real-world study comparing the clinical equivalence of trastuzumab biosimilar HLX02 and reference trastuzumab in the treatment of HER-2-positive breast cancer.

As the first trastuzumab biosimilar introduced in China, there are few studies on the clinical application of HLX02, especially in combination with other antitumour drugs, for the treatment of HER-2-positive breast cancer. A multicenter retrospective study was conducted in three hospitals in China to select patients with HER-2-positive breast cancer who met the inclusion criteria and received HLX02 or the reference trastuzumab. Ninety-six patients diagnosed with HER-2-positive breast cancer were finally included and divided into two groups and treated with HLX02 or the reference trastuzumab. The results showed no significant differences in pathological complete response (70.0% vs. 76.2%; P=1.000) and overall response rate (91.9% vs. 94.9%; P=0.673) between the two groups. Kaplan-Meier survival curves also showed no significant difference in time-to-event variables between the two groups (log-rank P=0.48). Safety was also comparable in both groups. In conclusion, among patients with HER2-positive breast cancer, HLX02 demonstrated equivalent efficacy and safety to its reference trastuzumab, both in neoadjuvant chemotherapy and in postoperative adjuvant therapy. However, clinical equivalence studies between HLX02 and the original trastuzumab drug remain challenging. Future research should focus on the clinical exchange between biosimilars and original drugs, as well as the extrapolation of biosimilars' indications.

Fine-grained weed recognition using Swin Transformer and two-stage transfer learning.

Weeding is very critical for agriculture due to its importance for reducing crop yield loss. Accurate recognition of weed species is one of the major challenges for achieving automatic and precise weeding. To improve the recognition performance of weeds and crops with similar visual characteristics, a fine-grained weed recognition method based on Swin Transformer and two-stage transfer learning is proposed in this study. First, the Swin Transformer network is introduced to learn the discriminative features that can distinguish subtle differences between visually similar weeds and crops. Second, a contrastive loss is applied to further enlarge the feature differences between different categories of weeds and crops. Finally, a two-stage transfer learning strategy is proposed to address the problem of insufficient training data and improve the accuracy of weed recognition. To evaluate the effectiveness of the proposed method, we constructed a private weed dataset (MWFI) with maize seedling and seven species of associated weeds that are collected in the farmland environment. The experimental results on this dataset show that the proposed method achieved the recognition accuracy, precision, recall, and F1 score of 99.18%, 99.33%, 99.11%, and 99.22%, respectively, which are superior to the performance of the state-of-the-art convolutional neural network (CNN)-based architectures including VGG-16, ResNet-50, DenseNet-121, SE-ResNet-50, and EfficientNetV2. Additionally, evaluation results on the public DeepWeeds dataset further demonstrate the effectiveness of the proposed method. This study can provide a reference for the design of automatic weed recognition systems.

Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review.

Purpose: The effect and safety of Semaglutide and Liraglutide on weight loss in people with obesity or overweight were evaluated by a Network Meta-Analysis system to provide an evidence-based reference for clinical treatment. Methods: Computer searched PubMed, Embase, and Cochrane Library databases to collect Liraglutide and Semaglutide injection monotherapy RCTs until April 2022, using Stata 16 software for Network Meta-Analysis. Results: Twenty-three RCTs study with 11,545 patients and 4 interventions (semaglutide 2.4mg, semaglutide 1.0mg, liraglutide 3.0mg and liraglutide 1.8 mg) were finally included. In terms of efficacy, semaglutide 2.4mg (-12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (-5.24 kg), semaglutide 1.0mg (-3.74 kg) and liraglutide 1.8mg (-3.29 kg). In terms of decreased HbA1c, semaglutide 2.4mg (MD=-1.48%, 95% CI [-1.93, -1.04]), semaglutide 1.0mg (MD=-1.36%, 95% CI [-1.72, -1.01]), liraglutide 1.8mg (MD=-1.23%, 95%Cl [-1.66, -0.80]) more effective than placebo. In terms of safety, the total incidence of adverse events was semaglutide 2.4mg > liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 1.0mg compare to placebo, the incidence of serious adverse events was liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 2.4mg > semaglutide 1.0mg, the incidence of hypoglycemic events was semaglutide 2.4mg > liraglutide 3.0mg > semaglutide 1.0mg > liraglutide 1.8mg. Conclusion: This meta-analysis indicates that all GLP-1RAs were more efficacious than placebo in people with obesity or overweight on efficacy. Semaglutide 2.4mg has an absolute advantage in weight loss and decreased HbA1c, but the incidence of total adverse events is also the highest and can cause hypoglycemia. In addition, although liraglutide 3.0mg was less effective than semaglutide 2.4mg, serious adverse events were still the most elevated.

Efficacy and safety of proton pump inhibitors versus vonoprazan in treatment of erosive esophagitis: A PRISMA-compliant systematic review and network meta-analysis.

BACKGROUND: Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE. METHODS: Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment. RESULTS: A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo. CONCLUSIONS: Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.

Recombinant Virus-like Particles of Human Parvovirus B19 with the Internal Location of VP1 Unique Region Produced by Hansenula polymorpha.

Human parvovirus B19 (HPV B19) is pathogenic to human, which can cause fifth disease, transient aplastic crisis, arthritis, myocarditis, autoimmune disorders, hydrops fetalis, and so on. Currently, no approved vaccines or antiviral drugs are available against HPV B19, and thus the development of effective vaccines is needed. The capsid of HPV B19 is composed of two types of proteins, i.e., the major capsid protein VP2 and the minor protein VP1. Previous experimental studies have shown that the dominant immune responses against HPV B19 are elicited by VP1, especially the unique region on the N-terminus of VP1. It has been found that VP2 alone or VP2 and VP1 together can assemble into virus-like particle (VLP). The VLP structure formed by VP2 has been resolved, however, the location of VP1 in the capsid, especially the location of VP1 unique region with strong immunogenicity, is still not clear. In the present work, using the Hansenula polymorpha expression system developed by our laboratory, two kinds of recombinant HPV B19 VLPs were expressed, i.e., the VLP co-assembled by VP1 and VP2 (VP1/VP2 VLP) and the VLP whose VP1 content was improved (VP1h/VP2 VLP). The expression, purity, and morphology of these two VLPs were characterized, and then their immunogenic properties were investigated and compared with those of the VLP containing VP2 alone (VP2 VLP) previously developed by our group. Furthermore, the location of the VP1 unique region in the VLPs was determined by using the immunogold electron microscopy (IGEM). Our experimental results show that the VP1h/VP2 VLP elicits a stronger neutralization against the HPV B19 than VP2 and VP1/VP2 VLPs, which implies that the increase of VP1 content significantly improves the level of neutralizing antibodies. In addition, the IGEM observations suggest that the unique region of VP1 may be located inside the recombinant VLP. The VLPs recombinantly expressed by our Hansenula polymorpha system may serve as a promising candidate immunogen for HPV B19 vaccine development.

A Health Technology Assessment Based on Chinese Guidelines: Glucagon-Like Peptide-1 Receptor Agonist in the Treatment of Type 2 Diabetes Complicated with Cardiovascular Disease.

Purpose: According to the requirements of the "Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions", this health technology assessment provides an evidence-based basis for drug selection and rational clinical use of glucagon-like peptide-1 receptor agonist drugs in medical institutions. Methods: We consult the drug instructions, clinical treatment guidelines and search relevant documents in databases such as China national knowledge infrastructure, Wanfang, PubMed, and government websites such as National Medical Products Administration, Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency to collect and sort out the relevant information of the indications, pharmacological effects, guideline recommendations, drug prices and other information of glucagon-like peptide-1 receptor agonists, using a percentile system systematically evaluate the five dimensions of glucagon-like peptide-1 receptor agonists in terms of pharmaceutical properties, efficacy, safety, economy, and other attributes. Results: The final scores of the evaluation results from high to low are semaglutide (71.00 points), dulaglutide (68.75 points), liraglutide (67.50 points), exenatide (67.00 points), lixisenatide (63.50 points), polyethylene glycol loxenatide (58.00 points) and benaglutide (49.00 points). Conclusion: In clinical practice, semaglutide and dulaglutide are the top two drugs that can be used as recommended drugs. This health technology assessment can provide an evidence-based basis for hospital selection and rational use of glucagon-like peptide-1 receptor agonists. Clinicians can rationally choose and use drugs according to the patient's conditions and needs.

Rituximab biosimilar HLX01 versus reference rituximab in the treatment of diffuse large B-cell lymphoma: Real-world clinical experience.

INTRODUCTION: HLX01 is the first rituximab biosimilar produced in China and the first monoclonal antibody biosimilar marketed in China. The purpose of this study was to comprehensively evaluate whether HLX01 is clinically consistent with the original drug based on real-world data to provide evidence for the clinical substitution of biosimilars in China. METHODS: A single-center retrospective study was conducted to select patients with diffuse large B-cell lymphoma who met the inclusion criteria and were treated with HLX01 or reference rituximab. Baseline characteristics, efficacy and safety results were recorded, and the corresponding statistical analysis was performed for various indicators. RESULTS: Thirty-three patients diagnosed with diffuse large B-cell lymphoma were included and divided into two groups that received HLX01 or reference rituximab. The results showed no significant difference in the overall response rate (86.7% vs. 88.9%; p = 1.000) or complete response rate (46.7% vs. 55.6%; p = 0.889) between the two groups. Kaplan-Meier survival curves also showed no significant difference in time-to-event variables between the two groups (log-rank = 0.244). Safety was also comparable in both groups. CONCLUSIONS: HLX01 is a suitable replacement for reference rituximab in the treatment of diffuse large B-cell lymphoma and is relatively inexpensive, thereby reducing the economic burden of patients. Nevertheless, the conclusion of this study still needs to be further validated by large-sample real-world data and explored for HLX01 in other indications, such as follicular lymphoma. CLINICAL TRIAL REGISTRATION: Not applicable.

Trastuzumab biosimilar HLX02 versus reference trastuzumab in patients with recurrent or metastatic HER2-positive breast cancer: a model-based economic evaluation for China.

BACKGROUND: HLX02 is a newly marketed trastuzumab biosimilar in China, but whether its price reflects a potential benefit in terms of its value remains unclear. In addition, the development of biosimilars in China is just beginning, and the state encourages health economic evaluation of newly marketed biosimilars. METHODS: Based on the previously published randomized controlled trial data, a Markov model was used to perform health economic evaluation of HLX02 and trastuzumab in the treatment of HER2-positive recurrent or metastatic breast cancer, calculate quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER), and evaluate the robustness of the model with sensitivity analysis. RESULTS: The model results showed that the 5-year mortality rate was 84.4% in the HLX02 group, while the mortality rate was 91.2% in the trastuzumab group. When without accounting for the cost of second-line treatment, patients treated with HLX02 had an increased life expectancy of 0.138 QALYs and a $421.11 lower cost compared with patients in the trastuzumab group, with an ICER value of -$3,051.52/QALY. CONCLUSIONS: At the willingness-to-pay threshold of $37,653/QALY in China, HLX02 is more cost-effective than trastuzumab. However, the relevant systems for the regulation of biosimilars still need to be improved.

Metastatic HER-2 positive breast cancer poses a considerable cost to society due to limitations in health care resources. HLX02 is the first trastuzumab biosimilar produced in China and evaluated worldwide, and its emergence has opened the door to trastuzumab biosimilars in China. Although HLX02 has been shown to be clinically equivalent to the original drug in the treatment of metastatic HER2-positive breast cancer, it remains unclear whether its price reflects the potential benefit in terms of its value. In addition, the development of biosimilars in China is just beginning, and the state encourages health economic evaluation of newly marketed biosimilars. Based on the results of Markov model, at the willingness-to-pay threshold of $37,653/QALY in China, HLX02 is more cost-effective than trastuzumab under the condition of equivalent efficacy and safety. However, it remains challenging to adjust the development of the regulation of biosimilars, such as the price difference between biosimilars and original drugs.

Evaluation of favipiravir in the treatment of COVID-19 based on the real-world.

BACKGROUND: The role of favipiravir (FVP) as a COVID-19 treatment is recognized but not fully elucidated. We aimed to evaluate whether FVP has definite clinical efficacy and safety in the treatment of COVID-19. METHODS: International and Chinese databases were searched for randomized controlled clinical trials evaluating FVP for the treatment of COVID-19. A meta-analysis was performed and published literature was synthesized to evaluate the corresponding therapeutic effects. RESULTS: We included 13 studies (1430 patients in total). Meta-analysis showed that patients with mild-to-moderate disease treated with FVP had a significantly higher viral clearance rate than those in the control group 10 and 14 days after initiation of treatment [RR: 1.13 (95% CI: 1.00, 1.28), P = 0.04; I2 = 39% for day 10 and RR: 1.16 (95% CI: 1.04, 1.30), P = 0.008; I2 = 38% for day 14] and a significantly shorter hospital stay [MD: -1.52 (95% CI: -2.82, -0.23), P = 0.02; I2 = 0%]. CONCLUSIONS: FVP significantly promotes viral clearance and reduces the hospitalization duration in mild-to-moderate COVID-19 patients, which can reduce the risk of severe disease outcomes in patients. However, more importantly, the results showed no benefit of FVP in severe patients, and caution should be taken regarding the treatment options of FVP in severe patients.

PLAIN LANGUAGE SUMMARYThe urgent need to identify effective interventions to treat novel coronavirus infections is a major challenge. The role of favipiravir (FVP) as a COVID-19 treatment is recognized but not fully elucidated. Our study showed a significant correlation between viral clearance and the promotion of clinical improvement with FVP in mild-to-moderate patients, which is significant for reducing the length of hospital stay of patients, reducing the risk of patients progressing to severe disease, thereby reducing mortality. However, the results showed no benefit of FVP in severe patients and the conclusion of this study still needs to be further verified by clinical trials with large samples.