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Scandinavian Journal of Gastroenterology 2009Due to the crucial role played by adhesion molecules in the pathogenesis of Crohn's disease (CD), targeting of these molecules has recently been proposed as a new... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Due to the crucial role played by adhesion molecules in the pathogenesis of Crohn's disease (CD), targeting of these molecules has recently been proposed as a new direction for the development of anti-inflammatory strategies for CD. The aim of this study was to provide up-to-date evidence on the effectiveness and safety of anti-adhesion molecule therapy in treating active CD.
MATERIAL AND METHODS
We studied articles retrieved by PubMed, EMBASE, the Cochrane Library and the Science Citation Index for randomized controlled trials (RCTs) relevant to CD and anti-adhesion molecule therapy.
RESULTS
Seven RCTs comparing anti-adhesion molecule therapy with placebo were included in a meta-analysis to evaluate the efficacy and safety of anti-adhesion molecule strategies in active CD. On the basis of pooled results of the seven RCTs (n = 2228), we found a significant difference in clinical remission rates between groups [relative risk (RR) 1.31, 95% confidence interval (CI) 1.12-1.52, fixed-effect model]. Five RCTs (n = 2178) compared the response rates of anti-adhesion molecule therapy and placebo; in overall analysis, anti-adhesion molecule therapy was effective for active CD (RR 1.28, 95% CI 1.16-1.42, random-effect model). In five studies enrolling 1867 individuals, anti-adhesion molecule therapy did not increase adverse events (RR 1.03, 95% CI 0.98-1.08, fixed-effect model).
CONCLUSIONS
Anti-adhesion molecule therapy, which could prevent leukocyte recruitment, was effective and safe for treating active CD. Because of the small number of studies included in this meta-analysis, the results should be interpreted with caution.
Topics: Antibodies, Monoclonal; Cell Adhesion Molecules; Crohn Disease; Humans; Immunologic Factors; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 19883269
DOI: 10.3109/00365520903367254 -
International Journal of Antimicrobial... Mar 2024This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to explore the efficacy and safety of small-molecule antivirals for treating coronavirus disease 2019 (COVID-19).
METHODS
Seven databases were searched from their inception to 01 June 2023. The risk of bias in randomised controlled trials and retrospective studies was evaluated individually using the Cochrane risk-of-bias tool and Newcastle Ottawa Scale.
RESULTS
In total, 160 studies involving 933 409 COVID-19 patients were evaluated. Compared with placebo or standard of care, proxalutamide demonstrated remarkable efficacy in reducing mortality rates, hospitalisation rates, serious adverse events, and the need for mechanical ventilation. Furthermore, it significantly enhanced both the rate of clinical improvement and expedited the duration of clinical recovery when compared with control groups. In patients with mild-to-moderate COVID-19, proxalutamide exhibited the above advantages, except for mortality reduction. Triazavirin was the most effective treatment for reducing the time required for viral clearance and improving the discharge rate. Leritrelvir and VV116 were ranked first in terms of enhancing the viral clearance rate on days 7 and 14, respectively. Molnupiravir was the most effective treatment for reducing the need for oxygen support. Overall, these findings remained consistent across the various subgroups.
CONCLUSIONS
A thorough evaluation of effectiveness, applicable to both mild-to-moderate and unstratified populations, highlights the specific advantages of proxalutamide, nirmatrelvir/ritonavir, triazavirin, azvudine, molnupiravir, and VV116 in combating COVID-19. Additional clinical data are required to confirm the efficacy and safety of simnotrelvir/ritonavir and leritrelvir. The safety profiles of these antivirals were deemed acceptable.
Topics: Humans; Network Meta-Analysis; COVID-19; Retrospective Studies; Ritonavir; Antiviral Agents; Cytidine; Hydroxylamines
PubMed: 38244811
DOI: 10.1016/j.ijantimicag.2024.107096 -
Inflammatory Bowel Diseases Apr 2024Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients undergoing organ transplantation are often on immunosuppressing medications to prevent rejection of the transplant. The data on use of concomitant immunosuppression for inflammatory bowel disease (IBD) and organ transplant management are limited. This study sought to evaluate the safety of biologic and small molecule therapy for the treatment of IBD among solid organ transplant recipients.
METHODS
Medline, Embase, and Web of Science databases were systematically searched for studies reporting on safety outcomes associated with the use of biologic and small molecule therapy (infliximab, adalimumab, certolizumab, golimumab, vedolizumab, ustekinumab, and tofacitinib) in patients with IBD postsolid organ transplant (eg, liver, kidney, heart, lung, pancreas). The primary outcome was infectious complications. Secondary outcomes included serious infections, colectomy, and discontinuation of biologic therapy.
RESULTS
Seven hundred ninety-seven articles were identified for screening, yielding 16 articles for the meta-analyses with information on 163 patients. Antitumor necrosis factor α (Anti-TNFs; infliximab and adalimumab) were used in 8 studies, vedolizumab in 6 studies, and a combination of ustekinumab or vedolizumab and anti-TNFs in 2 studies. Two studies reported outcomes after kidney and cardiac transplant respectively, whereas the rest of the studies included patients with liver transplants. The rates of all infections and serious infections were 20.09 per 100 person-years (100-PY; 95% CI, 12.23-32.99 per 100-PY, I2 = 54%) and 17.39 per 100-PY (95% CI, 11.73-25.78 per 100-PY, I2 = 21%), respectively. The rates of colectomy and biologic medication discontinuation were 12.62 per 100-PY (95% CI, 6.34-25.11 per 100-PY, I2 = 34%) and 19.68 per 100-PY (95% CI, 9.97-38.84 per 100-PY, I2 = 74%), respectively. No cases of venous thromboembolism or death attributable to biologic use were reported.
CONCLUSION
Biologic therapy is overall well tolerated in patients with solid organ transplant. Long-term studies are needed to better define the role of specific agents in this patient population.
Topics: Humans; Adalimumab; Biological Products; Inflammatory Bowel Diseases; Infliximab; Organ Transplantation; Ustekinumab
PubMed: 37300512
DOI: 10.1093/ibd/izad108 -
Expert Review of Clinical Pharmacology May 2022Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Statins might prevent cell adhesion to the endothelium, a key step in atherosclerosis. We conducted a systematic review and meta-analysis of the effect of statins on soluble vascular (sVCAM-1) and intercellular (sICAM-1) adhesion molecule 1.
METHODS
A systematic literature search was conducted in PubMed, Web of Science, and Scopus, from inception to July 2021. Risk of bias and certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist for analytical studies and GRADE, respectively.
RESULTS
Statins significantly reduced both sVCAM-1 (standard mean difference, SMD = -0.28, 95% CI -0.44 to -0.12, p = 0.001; 46 treatment arms; low certainty of evidence) and sICAM-1 (SMD = -0.75, 95% CI -1.00 to -0.50, p < 0.001; 61 treatment arms; moderate certainty of evidence) concentrations. In sensitivity analysis, the SMD values were not modified when individual studies were sequentially removed. There were significant associations between SMD and publication year and, for sICAM-1, statin-induced changes in HDL-cholesterol. In subgroup analysis, the lowering effect was significant with lipophilic, but not hydrophilic, statins, and similar, for sICAM-1, in participants with or without clinically overt atherosclerosis.
CONCLUSIONS
Statins significantly lower sVCAM-1/sICAM-1. Prospective studies are required to determine whether this mediates their atheroprotective effects (PROSPERO registration number: CRD42021276825).
Topics: Atherosclerosis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Intercellular Adhesion Molecule-1; Prospective Studies; Vascular Cell Adhesion Molecule-1
PubMed: 35485866
DOI: 10.1080/17512433.2022.2072294 -
Planta Mar 2023EF have been explored for its beneficial impact on environment and for its commercial applications. It has proved its worth in these sectors and showed an impact on... (Review)
Review
EF have been explored for its beneficial impact on environment and for its commercial applications. It has proved its worth in these sectors and showed an impact on biological properties of plants by producing various bioactive molecules and enzymes. Endophytes are plant mutualists that live asymptomatically within plant tissues and exist in almost every plant species. Endophytic fungi benefit from the host plant nutrition, and the host plant gains improved competitive abilities and tolerance against pathogens, herbivores, and various abiotic stresses. Endophytic fungi are one of the most inventive classes which produce secondary metabolites and play a crucial role in human health and other biotic aspects. This review is focused on systematic study on the biodiversity of endophytic fungi in plants, and their role in enhancing various properties of plants such as antimicrobial, antimycobacterial, antioxidant, cytotoxic, anticancer, and biological activity of secondary metabolites produced by various fungal endophytes in host plants reported from 1994 to 2021. This review emphasizes the endophytic fungal population shaped by host genotype, environment, and endophytic fungi genotype affecting host plant. The impact of endophytic fungi has been discussed in detail which influences the commercial properties of plants. Endophytes also have an influence on plant productivity by increasing parameters such as nutrient recycling and phytostimulation. Studies focusing on mechanisms that regulate attenuation of secondary metabolite production in EF would provide much needed impetus on ensuring continued production of bioactive molecules from a indubitable source. If this knowledge is further extensively explored regarding fungal endophytes in plants for production of potential phytochemicals, then it will help in exploring a keen area of interest for pharmacognosy.
Topics: Antioxidants; Biodiversity; Endophytes; Fungi; Plants; Plant Physiological Phenomena
PubMed: 36856911
DOI: 10.1007/s00425-023-04087-2 -
Journal of the American Academy of... Jul 2021Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Various systemic immunomodulating therapies have been investigated to treat nail psoriasis, but the efficacy remains unclear.
OBJECTIVE
To perform a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis.
METHODS
Eligible studies in online databases were identified until March 10, 2020. To assess the efficacy of small molecule inhibitors and biologics, network meta-analyses with surface under the cumulative ranking curve of improvement in nail score at 10 to 16 and at 24 to 26 weeks, as well as 100% improvement of Nail Psoriasis Severity Index (NAPSI), were performed.
RESULTS
Thirty-nine studies with a total of 13 treatment arms involving 15,673 patients with nail psoriasis were included. An network meta-analysis showed that tofacitinib (weighted mean difference, 56.67; 95% confidence interval [CI], 35.87-77.48) and ixekizumab (weighted mean difference, 59.40; 95% CI, 45.87-72.93) presented the most improvement of nail score at 10 to 16 weeks and 24 to 26 weeks, respectively. For 100% improvement of the Nail Psoriasis Severity Index, ixekizumab showed the best efficacy among all treatments (odds ratio, 2.98; 95% CI, 1.74-5.10).
LIMITATIONS
Insufficiency of eligible data and no long-term follow-up data.
CONCLUSION
Tofacitinib and ixekizumab presented the best efficacy for treating nail psoriasis in 10 to 16 weeks and 24 to 26 weeks, respectively.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Dermatologic Agents; Etanercept; Humans; Infliximab; Nail Diseases; Network Meta-Analysis; Piperidines; Protein Kinase Inhibitors; Psoriasis; Pyrimidines; Severity of Illness Index
PubMed: 33482253
DOI: 10.1016/j.jaad.2021.01.024 -
Annals of Medicine 2023At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
At present, there are some randomized controlled trials (RCTs) of oral small molecule drugs. The purpose of this study was to evaluate the efficacy and safety of oral small molecule drug treatment for COVID-19.
METHODS
RCTs were identified through systematic searches of PubMed, Embase, and Cochrane Central Register of Controlled Trials through 1 April 2023. A total of nine RCTs were included, including 30,970 COVID-19 patients comparing five treatments (azvudine, molnupiravir, paxlovid, VV116, and placebo). The Cochrane risk of bias tool for randomized trials (RoB) was used to assess the bias risk of the included studies. The direct and indirect evidence were combined using a Bayesian network meta-analysis (PROSPERO Code No: CRD42023397837).
RESULTS
Direct analysis showed that paxlovid was associated with a reduced risk of mortality (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.06-0.25) and hospitalization (OR = 0.04, 95% CI: 0.00-0.67) compared with placebo. Network meta-analysis showed that paxlovid had the highest probability of being the best management strategy in patients with COVID-19, reducing mortality (OR = 0.11, 95% CI: 0.01-1.99; surface under the cumulative ranking curve [SUCRA]: 0.77) and hospitalization (OR = 0.06, 95% CI: 0.00-1.03; SUCRA: 0.95). For prespecified safety outcomes, SUCRA values ranked VV116 (OR = 0.09, 95% CI: 0.00-2.07: SUCRA 0.86) as the most beneficial intervention for the prevention of serious adverse events.
CONCLUSIONS
When compared to other antiviral medications, paxlovid can reduce the mortality and hospitalization of COVID-19 patients.
Topics: Humans; COVID-19; Network Meta-Analysis
PubMed: 37967171
DOI: 10.1080/07853890.2023.2274511 -
Drugs in R&D Mar 2017Psoriasis is an immune-mediated inflammatory disease for which treatment has evolved over the past few years due to the introduction of immunobiologic and small molecule... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Psoriasis is an immune-mediated inflammatory disease for which treatment has evolved over the past few years due to the introduction of immunobiologic and small molecule inhibitor medications. A better understanding of the comparative efficacies of drugs may help doctors to choose the most appropriate treatment for patients.
OBJECTIVE
The aim of this study was to conduct a systematic review and meta-analysis to assess the efficacy of immunobiologic and small molecule inhibitor drugs for patients with moderate to severe psoriasis.
DATA SOURCES
The EMBASE, PUBMED, LILACS, Web of Science and ClinicalTrials.org databases were searched for trials published to 21 July 2016.
STUDY SELECTION
Only randomized, double-blind, placebo-controlled clinical trials that evaluated the efficacy of immunobiologics or small molecule inhibitors for moderate to severe plaque-type psoriasis were selected by two independent authors. No restrictions were used.
DATA EXTRACTION AND SYNTHESIS
Two authors independently extracted the data and a random-effects model meta-analysis was performed.
MAIN OUTCOMES AND MEASURES
The Psoriasis Area and Severity Index (PASI) 75 was considered the primary outcome, measured at the primary endpoint of each study.
RESULTS
Thirty-eight studies were included in our analysis. The overall pooled effect favored biologics and small molecule inhibitors over placebo (risk difference [RD] 0.59, 95% confidence interval [CI] 0.58-0.60). Ixekizumab at a dose of 160 mg on week 0 and then every 2 weeks (RD 0.84, 95% CI 0.81-0.88), brodalumab 210 mg (RD 0.79, 95% CI 0.76-0.82), infliximab 5 mg/kg (RD 0.76, 95% CI 0.73-0.79), and secukinumab 300 mg (RD 0.76, 95% CI 0.71-0.81) showed a greater chance of response (PASI 75) when compared with placebo.
LIMITATIONS
The methodology of a traditional meta-analysis does not allow for drugs to be ranked. Included studies used short-term endpoints (10-16 weeks) to evaluate the primary outcome, therefore long-term efficacy could not be determined.
CONCLUSIONS AND RELEVANCE
The anti-IL-17 drugs brodalumab, ixekizumab and secukinumab showed an equal or greater chance of helping patients achieve a 75% improvement on PASI compared with other reviewed drugs.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Humans; Psoriasis; Randomized Controlled Trials as Topic; Small Molecule Libraries
PubMed: 27838901
DOI: 10.1007/s40268-016-0152-x -
Medicina (Kaunas, Lithuania) Oct 2022Background and objective: Intercellular adhesion molecule-1 (ICAM-1) appears to be an active and important biomarker for decreasing the risk of cardiovascular issues... (Meta-Analysis)
Meta-Analysis Review
Background and objective: Intercellular adhesion molecule-1 (ICAM-1) appears to be an active and important biomarker for decreasing the risk of cardiovascular issues among individuals with obstructive sleep apnea (OSA). Herein, a systematic review and meta-analysis was designed to probe whether plasma/serum ICAM-1levels are different in adults with OSA compared to adults with no OSA, as well as adults with severe OSA compared to adults with mild/moderate OSA. Materials and methods: A thorough and systematic literature search was performed in four databases (PubMed/Medline, Web of Science, Scopus, and Cochrane Library) until 17 July 2022, without any age and sample size restrictions to retrieve the relevant articles. The standardized mean difference (SMD) along with a 95% confidence interval (CI) of plasma/serum of ICAM-1 levels was reported. Analyses, including sensitivity analysis, subgroup analysis, trial sequential analysis, meta-regression, and a funnel plot analysis, were performed in the pooled analysis. Results: A total of 414 records were identified in the databases, and 17 articles including 22 studies were entered into the meta-analysis. The pooled SMD of serum/plasma ICAM-1 levels in adults with OSA compared to controls was 2.00 (95%CI: 1.41, 2.59; p < 0.00001). The pooled SMD of serum/plasma ICAM-1 levels in adults with severe compared to mild/moderate OSA was 3.62 (95%CI: 1.74, 5.51; p = 0.0002). Higher serum/plasma ICAM-1 levels were associated with a higher mean age of controls, higher scores for the apnea-hypopnea index, and with a lower mean age of adults with OSA and with smaller sample sizes. Conclusions: Th results of the present meta-analysis showed that serum/plasma ICAM-1 levels in adults with OSA was higher than serum/plasma ICAM-1 levels in controls. Similarly, serum/plasma ICAM-1 levels in adults with severe OSA were higher compared to serum/plasma ICAM-1 levels of adults with mild or moderate OSA. Therefore, ICAM-1 may be used as an additional diagnostic and therapeutic biomarker in adults with OSA.
Topics: Adult; Humans; Intercellular Adhesion Molecule-1; Sleep Apnea, Obstructive; Biomarkers
PubMed: 36295659
DOI: 10.3390/medicina58101499 -
Neurology and Therapy Dec 2023Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most... (Review)
Review
Immunotherapies Targeting Amyloid and Tau Protein in Alzheimer's Disease: Should We Move Away from Diseases and Focus on Biological Targets? A Systematic Review and Expert Opinion.
INTRODUCTION
Alzheimer's disease (AD) is the most common cause of dementia worldwide, making it a major public health issue. Anti-amyloid and anti-tau antibodies are the most advanced therapeutic approach at present. Three drugs (lecanemab, donanemab and aducanumab) are on track to be marketed in the coming months. In this systematic review, we review all Phase 2 and Phase 3 clinical trials conducted in this indication and the particularities of the molecules tested.
METHODS
The PubMed and ClinicalTrials.gov databases were searched through February 2023 for Phase 2 and 3 clinical trials involving passive anti-amyloid or anti-tau immunotherapies with published results. This review has been compiled in compliance with the PRISMA checklists.
RESULTS
Of the 165 studies found and after eliminating duplicates, 40 studies had their results published on PubMed and/or ClinicalTrials.gov. Eight anti-amyloid molecules and four anti-tau molecules were the subject of Phase 2 studies, seven anti-amyloids were the subject of Phase 3 trials, and two molecules were granted early marketing approval by the US Food and Drug Administration (FDA). The results were compiled in summary tables showing the primary endpoints used, results, age of the study population and specific adverse events for these molecules.
DISCUSSION
Passive immunotherapy in AD is largely dominated by anti-amyloid antibodies, which are more numerous and more advanced in the pipeline. Lecanemab, donanemab and aducanumab are distinguished by their relative efficacy in terms of cognitive and functional evaluation but also by a decrease in amyloid and tau proteins in the brain. These three molecules have in common that they bind to N-terminal ends of amyloid fibrils and plaques. The findings of their studies raise the question of which criteria to apply when choosing which patient will receive them when marketed, such as the apoliprotein E gene's fourth allele (APOE4) genetic status of patients. The large number of negative studies may also raise the question of the criteria for defining the disease and the possible interest in redefining it on biological grounds to offer a more personalized medicine to patients suffering from neurodegenerative diseases.
PubMed: 37812325
DOI: 10.1007/s40120-023-00541-1