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BMJ Open Ophthalmology Jun 2024Graves' ophthalmopathy is a complex autoimmune disorder that can significantly affect quality of life (QoL), vision and physical appearance. Recently, a deeper...
BACKGROUND
Graves' ophthalmopathy is a complex autoimmune disorder that can significantly affect quality of life (QoL), vision and physical appearance. Recently, a deeper understanding of the underlying pathogenesis has led to the development of novel treatment options.
AIMS
The purpose of this review is to explore the current literature on conventional and novel treatment modalities and to evaluate which interventions provide the most favourable psychological and clinical outcomes in patients with moderate to severe, active Grave's ophthalmopathy. For example, QoL is an important psychosocial outcome of disease management. However, available literature demonstrates that not all clinically effective treatment options improve patients' QoL.
METHODS
A systematic literature review was conducted to assess the clinical and psychosocial outcomes of different therapies for Graves' ophthalmopathy. An extensive database search of Ovid Medline, Ovid Embase and Cochrane Central Register of Controlled Trials was conducted. Studies generated were reviewed and the relevant selected data were retrieved and analysed.
RESULTS
Results showed intravenous steroids, rituximab (RTX), tocilizumab and teprotumumab were all significantly effective in improving Clinical Activity Scores. Orbital radiotherapy showed a slight improvement in proptosis and diplopia. All interventions were safe with few serious adverse events being reported across all studies. All treatment modalities demonstrated beneficial improvements in both components of the Graves' Ophthalmopathy-QoL (QoL) questionnaire, apart from orbital radiotherapy which only demonstrated improvements in the visual functioning subscale. Teprotumumab was identified to be the most effective intervention for improving both clinical and psychosocial outcomes. However, further research needs to be conducted to evaluate its side effect profile and cost-effectiveness. Nonetheless, with time it has the potential to be a first-line treatment option in the management of active moderate to severe Graves' ophthalmopathy.
Topics: Humans; Graves Ophthalmopathy; Quality of Life; Antibodies, Monoclonal, Humanized; Rituximab; Immunologic Factors; Glucocorticoids
PubMed: 38886120
DOI: 10.1136/bmjophth-2023-001515 -
Medicine International 2024The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing...
The present systematic review evaluated the effectiveness of anti-EGFR therapy in combination with radiotherapy (RT) or with chemoradiation compared with the existing standard of care for the treatment of locally advanced head and neck squamous cell carcinoma (LAHNSCC). The PubMed, SCOPUS, EMBASE and COCHRANE databases were searched and 12 phase III randomized controlled trials were included. The effectiveness of the anti-EGFR monoclonal antibody cetuximab was evaluated in nine trials. Nimotuzumab (one trial), zalutumumab (one trial) and panitumumab (one trial) were the monoclonal antibodies evaluated in the remaining three trials. One study tested the effectiveness of adding cetuximab to radical RT and found that patients with LAHNSCC exhibited improvement in locoregional control (LRC), overall survival (OS) and progression-free survival (PFS) compared with those of patients treated with RT alone. A total of three studies tested the effectiveness of adding an anti-EGFR agent to chemoradiation. Of these, a single institution study in which patients received cisplatin at 30 mg/m weekly, instead of the standard doses of 100 mg/m every 3 weeks or 40 mg/m every week, reported significant improvement in PFS with the addition of nimotuzumab to chemoradiotherapy without an improvement in overall survival. However, the other two studies indicated that, when added to standard chemoradiation, the anti-EGFR monoclonal antibodies cetuximab or zalutumumab did not improve survival outcomes. Two phase III trials evaluated RT plus an anti-EGFR agent compared with chemoradiation alone. Of these, one study reported inferior outcomes with cetuximab-RT in terms of OS and LRC, whereas the other study with panitumumab plus RT failed to prove the non-inferiority. Two trials evaluated induction chemotherapy followed by cetuximab-RT compared with chemoradiotherapy and reported no benefits in terms of OS or PFS. Furthermore, one study evaluated induction chemotherapy followed by cetuximab-RT compared with induction chemotherapy followed by chemoradiotherapy and found no improvement in OS or PFS. Finally, three phase III trials tested the effectiveness of cetuximab plus RT in the treatment of human papillomavirus-positive oropharyngeal carcinoma, and found it to be inferior compared with cisplatin-RT in terms of OS, PFS and failure-free survival. Based on the aforementioned findings, it is difficult to conclude that anti-EGFR therapy in any form has an advantage over conventional chemoradiation in the treatment of LAHNSCC.
PubMed: 38873325
DOI: 10.3892/mi.2024.165 -
Brain and Behavior Jun 2024The US Food and Drug Administration authorized lecanemab for the therapeutic use of Alzheimer's disease (AD) in January 2023. To assess the effectiveness and safety of...
PURPOSE
The US Food and Drug Administration authorized lecanemab for the therapeutic use of Alzheimer's disease (AD) in January 2023. To assess the effectiveness and safety of lecanemab in treating AD, we thoroughly examined the studies that are currently accessible.
METHOD
Preferred Reporting Items for Systematic Reviews and Meta-Analysis recommendations were followed. In order to find relevant studies on lecanemab, we carried out a thorough literature search utilizing the electronic databases MEDLINE via PubMed, Cochrane, Web of Science, EBSCOhost, and Scopus. Excluding any research using experimental animals, we looked at lecanemab's effectiveness and side effects in treating AD in human clinical trials. Three randomized controlled studies were included.
FINDINGS
According to studies, lecanemab lessens clinical deterioration and reduces brain amyloid-beta plaques (difference,.45; 95% confidence interval,.67 to.23; p < .001). Participants who received lecanemab saw a greater frequency of amyloid-related imaging abnormalities (ARIA)-H (17.3% vs. 9.0%) and ARIA-E (12.6% vs. 1.7%), which is a significant adverse outcome.
CONCLUSION
Lecanemab has been shown to have an impact on the two primary pathophysiologic indicators of AD (Aβ and tau). There are still a lot of unresolved issues related to lecanemab. Future research on the effectiveness and safety of lecanemab is advised in order to determine that the advantages of this medication exceed the disadvantages.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Brain; Plaque, Amyloid; Antibodies, Monoclonal, Humanized
PubMed: 38867460
DOI: 10.1002/brb3.3592 -
Alimentary Pharmacology & Therapeutics Jul 2024Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We... (Meta-Analysis)
Meta-Analysis Comparative Study Review
INTRODUCTION
Rapidity of effect of advanced therapies for patients with Crohn's disease (CD) can be an essential decision parameter; however, comparative evaluation is lacking. We aimed to compare early response for advanced CD therapies in a network meta-analysis (NMA).
METHODS
We searched systematically MEDLINE, Embase, and CENTRAL up to 19 February 2024, for randomised controlled trials. The co-primary outcomes were induction of clinical remission (Crohn's Disease Activity Index (CDAI) ≤150) and clinical response (≥100-point reduction in CDAI) within the first 6 weeks of treatment. We incorporated any assessment within this time point in a Bayesian random-effects NMA following PRISMA-NMA guidance (PROSPERO ID: CRD42022368509).
RESULTS
Twenty-five studies, comprising 7414 patients, were included. Infliximab combined with azathioprine or monotherapy ranked highest for induction of clinical remission within 6 weeks and was significantly superior to certolizumab, ustekinumab, guselkumab, vedolizumab, and upadacitinib. However, superiority over risankizumab 600 mg and adalimumab 160/80 mg was non-significant. Accordingly, infliximab in combination with azathioprine and guselkumab 600 mg ranked highest in the corresponding analysis of clinical response with no statistical significance demonstrated. Among bio-exposed patients, none of whom received infliximab, upadacitinib, and risankizumab induced the highest clinical responses. On the other hand, vedolizumab, certolizumab, and ustekinumab ranked lowest across the analyses.
CONCLUSIONS
We found infliximab to be ranked highest and superior to all other agents but risankizumab and adalimumab, demonstrating the highest probability of early induction of remission. Upadacitinib and risankizumab induced the highest clinical responses in bio-exposed patients. However, infliximab was not investigated in this population.
Topics: Humans; Crohn Disease; Network Meta-Analysis; Biological Products; Treatment Outcome; Randomized Controlled Trials as Topic; Drug Therapy, Combination; Infliximab; Gastrointestinal Agents; Remission Induction; Severity of Illness Index
PubMed: 38863153
DOI: 10.1111/apt.18110 -
New Microbes and New Infections 2024While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients... (Review)
Review
While mortality caused by sepsis remains an unsolved problem, studies showed conflicting results about effectiveness of monoclonal and polyclonal antibodies in patients suffering sepsis. For this reason, this current study provides an update of review clinical randomized trial studies until March 2024. The main object of this study is to determine effects of monoclonal and polyclonal antibodies on mortality rate and hospitalization of patients suffering sepsis. Search of Scopus, Web of science, EMBASE, PubMed and Cochrane were performed and randomized controlled trials which conducted in patients with septic shock or bacterial sepsis were included. Two reviewers assessed all searched trials for eligibility according to already defined criteria and did data collection and analyses afterwards. Present study showed monoclonal and polyclonal antibodies are a safe strategy with mild-to-moderate adverse effects. However, most studies indicate no significant change among inter-and intra-group comparison (p > 0.05) and further studies are needed, results showed an increase in survival rate, ventilator-and ICU-free days, resolve organ dysfunction, mediating inflammation related cytokines.
PubMed: 38860003
DOI: 10.1016/j.nmni.2024.101435 -
BMC Cancer Jun 2024Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Novel antibody-drug conjugates (ADCs) drugs present a promising anti-cancer treatment, although survival benefits for HER2-positive advanced breast cancer (BC) remain controversial. The aim of this meta-analysis was to evaluate the comparative effect of ADCs and other anti-HER2 therapy on progression-free survival (PFS) and overall survival (OS) for treatment of HER2-positive locally advanced or metastatic BC.
METHODS
Relevant randomized controlled trials (RCTs) were retrieved from five databases. The risk of bias was assessed with the Cochrane Collaboration's tool for RCTs by RevMan5.4 software. The hazard ratio (HR) and 95% confidence intervals (CIs) were extracted to evaluate the benefit of ADCs on PFS and OS in HER2-positive advanced BC by meta-analysis.
RESULTS
Meta-analysis of six RCTs with 3870 patients revealed that ADCs significantly improved PFS (HR: 0.63, 95% CI: 0.49-0.80, P = 0.0002) and OS (HR: 0.79, 95% CI: 0.72-0.86, P < 0.0001) of patients with HER2-positive locally advanced or metastatic BC. Subgroup analysis showed that PFS and OS were obviously prolonged for patients who previously received HER2-targeted therapy. Sensitivity analysis and publication bias suggested that the results were stable and reliable.
CONCLUSION
Statistically significant benefits for PFS and OS were observed with ADCs in HER2-positive locally advanced or metastatic BC, especially for those who received prior anti-HER2 treatment.
Topics: Humans; Breast Neoplasms; Receptor, ErbB-2; Female; Immunoconjugates; Randomized Controlled Trials as Topic; Progression-Free Survival; Treatment Outcome; Trastuzumab; Antineoplastic Agents, Immunological
PubMed: 38851684
DOI: 10.1186/s12885-024-12478-1 -
BMJ Open Jun 2024The aim of this study was to assess the clinical benefit value of approved antibody drug conjugates (ADCs) for solid tumours using the European Society for Medical...
Application of the ESMO Magnitude of Clinical Benefit Scale to assess the clinical benefit of antibody drug conjugates in solid cancer: a systematic descriptive analysis of phase III and pivotal phase II trials.
OBJECTIVE
The aim of this study was to assess the clinical benefit value of approved antibody drug conjugates (ADCs) for solid tumours using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) V.1.1.
DESIGN
Systematic descriptive analysis.
DATA SOURCES
PubMed was searched for publications from 1 January 2000 to 18 October 2023.
ELIGIBILITY CRITERIA
We included the phase III randomised controlled trials or phase II pivotal trials leading to approval of ADCs in solid tumours.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data and discrepancies were resolved by consensus in the presence of a third investigator.
RESULTS
ESMO-MCBS Scores were calculated for 16 positive clinical trials of eight ADCs, which were first approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), the China National Medical Products Administration and the Japanese Pharmaceuticals and Medical Devices Agency for solid cancers. Among 16 trials, 4 (25%) met the ESMO-MCBS benefit threshold grade, while 12 (75%) of the regimens did not meet the ESMO-MCBS benefit threshold grade. 5 (31%) of the 16 trials had no published scorecard on the ESMO website due to the approval by other jurisdictions but not by the FDA or EMA. Discrepancies between our results and the ESMO scorecard were observed in 4 (36%) of 11 trials, mostly owing to integration of more recent data.
CONCLUSIONS
ESMO-MCBS is an important tool for assessing the clinical benefit of cancer drugs, but not all drugs met the meaningful benefit threshold.
Topics: Humans; Neoplasms; Immunoconjugates; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Antineoplastic Agents; United States; Drug Approval
PubMed: 38851227
DOI: 10.1136/bmjopen-2023-077108 -
Annals of Allergy, Asthma & Immunology... Jun 2024Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in...
A systematic review and expert Delphi Consensus recommendation on the use of vaccines in patients receiving dupilumab: A position paper of the American College of Allergy, Asthma and Immunology.
BACKGROUND
Dupilumab is a monoclonal antibody that targets the interleukin (IL)-4 receptor alpha subunit, thus blocking the effects of IL-4 and IL-13, and has shown efficacy in treating various conditions including asthma, atopic dermatitis, eosinophilic esophagitis, and others. Because of its immune modulatory effects, clinical trials that studied dupilumab did not allow patients to receive live vaccines during the clinical trials because of an abundance of caution, and thus package inserts recommend that patients who are being treated with dupilumab should avoid live vaccines. Because dupilumab is now approved for use in patients from 6 months of age for the treatment of atopic dermatitis, this reported contraindication is now posing a clinical dilemma for patients and clinicians.
OBJECTIVE
To perform a systematic review of literature on the safety and efficacy of vaccinations in patients who are receiving dupilumab and to provide expert guidance on the use of vaccines in patients who are receiving dupilumab.
METHODS
A systematic review of the literature was performed, and an expert Delphi Panel was assembled.
RESULTS
The available literature on patients who received vaccinations while using dupilumab overall suggests that live vaccines are safe and that the vaccine efficacy, in general, is not affected by dupilumab. The expert Delphi panel agreed that the use of vaccines in patients receiving dupilumab was likely safe and effective.
CONCLUSION
Vaccines (including live vaccines) can be administered to patients receiving dupilumab in a shared decision-making capacity.
PubMed: 38848870
DOI: 10.1016/j.anai.2024.05.014 -
PloS One 2024Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparative efficacy of anti-vascular endothelial growth factor on diabetic macular edema diagnosed with different patterns of optical coherence tomography: A network meta-analysis.
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have emerged as the most common therapeutic approach for the management of diabetic macular edema (DME). Despite their proven superiority over other interventions, there is a paucity of data regarding the relative effectiveness of anti-VEGF agents in treating DME diagnosed with different patterns of optical coherence tomography (OCT). In this regard, we conducted a systematic review and comparative analysis of the therapeutic efficacy of intravitreal bevacizumab, ranibizumab, aflibercept, and conbercept in the management of DME with diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD) patterns identified using OCT. Our study encompassed a comprehensive search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and Wan Fang Data from their inception until January 25, 2023. The network meta-analysis involved the inclusion of 1606 patients from 20 retrospective studies with a moderate risk of bias but no evidence of publication bias. The DRT group had the highest increase in best-corrected visual acuity (BCVA) with anti-VEGF, while the SRD group had the greatest reduction in Central Macular Thickness (CMT). Furthermore, conbercept, ranibizumab, and bevacizumab, respectively, showed the best treatment outcomes for patients with DRT, CME, and SRD in terms of improvement in BCVA. And, conbercept exhibited the highest reduction in CMT in the DRT, CME, and SRD groups. In conclusion, our study highlights the efficacy of anti-VEGF agents in the management of DME and provides valuable insights into the selection of anti-VEGF agents tailored to the individual needs of patients.
Topics: Humans; Angiogenesis Inhibitors; Bevacizumab; Diabetic Retinopathy; Intravitreal Injections; Macular Edema; Network Meta-Analysis; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Tomography, Optical Coherence; Treatment Outcome; Vascular Endothelial Growth Factor A; Visual Acuity
PubMed: 38848379
DOI: 10.1371/journal.pone.0304283 -
Journal of Pharmaceutical Policy and... 2024Advances in targeted therapies have expanded the treatment options for colorectal cancer (CRC), allowing for more tailored and effective approaches to managing the...
BACKGROUND
Advances in targeted therapies have expanded the treatment options for colorectal cancer (CRC), allowing for more tailored and effective approaches to managing the disease. In targeted therapy, Bevacizumab is a commonly prescribed anti-VEGF monoclonal antibody that has a direct anti-vascular impact in cancer patients. Vascular Endothelial Growth Factors (VEGFs), especially VEGF-A, are significant agents in promoting tumour angiogenesis
OBJECTIVE
To assess the impact of adding Bevacizumab to chemotherapy on progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer.
METHODOLOGY
Comprehensive searches have been performed on electronic databases such as PubMed, and Google Scholar using the following terms: colorectal cancer, adenocarcinoma, Bevacizumab, chemotherapy, and monoclonal antibody.
RESULTS
In the meta-analysis, 16 out of the 24 included studies were analysed. In the final analysis, incorporating Bevacizumab with chеmothеrapy demonstrated favourable outcomes for OS with a hazard ratio (HR = 0.689,95%CI: 0.51-0.83, ² = 39%, p <0.01) and for PFS with a hazard ratio (HR = 0.77 95% CI: 0.60-0.96, I² = 54%, < 0.01). The subgroup analysis of PFS, categorised by study dеsign (prospеctivе vs rеtrospеctivе), reveals that the Hazard Ratio (HR = 0.82, 95% CI: 0.62-0.97, ² = 21%, < 0.01) and for OS with a hazard ratio (HR = 0.73, 95% CI: 0.52-0.86, I² = 17%, < 0.01).
CONCLUSION
Our findings indicate that combining Bevacizumab with chemotherapy enhances clinical outcomes and results in a significant increase in PFS and OS in patients with metastatic colorectal cancer. Positive outcomes are demonstrated by a substantial 23% increase in PFS and 31% increase in OS in patients with metastatic colorectal cancer who undergo Bevacizumab in conjunction with chemotherapy
PubMed: 38845624
DOI: 10.1080/20523211.2024.2354300