-
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 -
The Cochrane Database of Systematic... Feb 2018The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The prognosis of people with metastatic cutaneous melanoma, a skin cancer, is generally poor. Recently, new classes of drugs (e.g. immune checkpoint inhibitors and small-molecule targeted drugs) have significantly improved patient prognosis, which has drastically changed the landscape of melanoma therapeutic management. This is an update of a Cochrane Review published in 2000.
OBJECTIVES
To assess the beneficial and harmful effects of systemic treatments for metastatic cutaneous melanoma.
SEARCH METHODS
We searched the following databases up to October 2017: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS. We also searched five trials registers and the ASCO database in February 2017, and checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
We considered RCTs of systemic therapies for people with unresectable lymph node metastasis and distant metastatic cutaneous melanoma compared to any other treatment. We checked the reference lists of selected articles to identify further references to relevant trials.
DATA COLLECTION AND ANALYSIS
Two review authors extracted data, and a third review author independently verified extracted data. We implemented a network meta-analysis approach to make indirect comparisons and rank treatments according to their effectiveness (as measured by the impact on survival) and harm (as measured by occurrence of high-grade toxicity). The same two review authors independently assessed the risk of bias of eligible studies according to Cochrane standards and assessed evidence quality based on the GRADE criteria.
MAIN RESULTS
We included 122 RCTs (28,561 participants). Of these, 83 RCTs, encompassing 21 different comparisons, were included in meta-analyses. Included participants were men and women with a mean age of 57.5 years who were recruited from hospital settings. Twenty-nine studies included people whose cancer had spread to their brains. Interventions were categorised into five groups: conventional chemotherapy (including single agent and polychemotherapy), biochemotherapy (combining chemotherapy with cytokines such as interleukin-2 and interferon-alpha), immune checkpoint inhibitors (such as anti-CTLA4 and anti-PD1 monoclonal antibodies), small-molecule targeted drugs used for melanomas with specific gene changes (such as BRAF inhibitors and MEK inhibitors), and other agents (such as anti-angiogenic drugs). Most interventions were compared with chemotherapy. In many cases, trials were sponsored by pharmaceutical companies producing the tested drug: this was especially true for new classes of drugs, such as immune checkpoint inhibitors and small-molecule targeted drugs.When compared to single agent chemotherapy, the combination of multiple chemotherapeutic agents (polychemotherapy) did not translate into significantly better survival (overall survival: HR 0.99, 95% CI 0.85 to 1.16, 6 studies, 594 participants; high-quality evidence; progression-free survival: HR 1.07, 95% CI 0.91 to 1.25, 5 studies, 398 participants; high-quality evidence. Those who received combined treatment are probably burdened by higher toxicity rates (RR 1.97, 95% CI 1.44 to 2.71, 3 studies, 390 participants; moderate-quality evidence). (We defined toxicity as the occurrence of grade 3 (G3) or higher adverse events according to the World Health Organization scale.)Compared to chemotherapy, biochemotherapy (chemotherapy combined with both interferon-alpha and interleukin-2) improved progression-free survival (HR 0.90, 95% CI 0.83 to 0.99, 6 studies, 964 participants; high-quality evidence), but did not significantly improve overall survival (HR 0.94, 95% CI 0.84 to 1.06, 7 studies, 1317 participants; high-quality evidence). Biochemotherapy had higher toxicity rates (RR 1.35, 95% CI 1.14 to 1.61, 2 studies, 631 participants; high-quality evidence).With regard to immune checkpoint inhibitors, anti-CTLA4 monoclonal antibodies plus chemotherapy probably increased the chance of progression-free survival compared to chemotherapy alone (HR 0.76, 95% CI 0.63 to 0.92, 1 study, 502 participants; moderate-quality evidence), but may not significantly improve overall survival (HR 0.81, 95% CI 0.65 to 1.01, 2 studies, 1157 participants; low-quality evidence). Compared to chemotherapy alone, anti-CTLA4 monoclonal antibodies is likely to be associated with higher toxicity rates (RR 1.69, 95% CI 1.19 to 2.42, 2 studies, 1142 participants; moderate-quality evidence).Compared to chemotherapy, anti-PD1 monoclonal antibodies (immune checkpoint inhibitors) improved overall survival (HR 0.42, 95% CI 0.37 to 0.48, 1 study, 418 participants; high-quality evidence) and probably improved progression-free survival (HR 0.49, 95% CI 0.39 to 0.61, 2 studies, 957 participants; moderate-quality evidence). Anti-PD1 monoclonal antibodies may also result in less toxicity than chemotherapy (RR 0.55, 95% CI 0.31 to 0.97, 3 studies, 1360 participants; low-quality evidence).Anti-PD1 monoclonal antibodies performed better than anti-CTLA4 monoclonal antibodies in terms of overall survival (HR 0.63, 95% CI 0.60 to 0.66, 1 study, 764 participants; high-quality evidence) and progression-free survival (HR 0.54, 95% CI 0.50 to 0.60, 2 studies, 1465 participants; high-quality evidence). Anti-PD1 monoclonal antibodies may result in better toxicity outcomes than anti-CTLA4 monoclonal antibodies (RR 0.70, 95% CI 0.54 to 0.91, 2 studies, 1465 participants; low-quality evidence).Compared to anti-CTLA4 monoclonal antibodies alone, the combination of anti-CTLA4 plus anti-PD1 monoclonal antibodies was associated with better progression-free survival (HR 0.40, 95% CI 0.35 to 0.46, 2 studies, 738 participants; high-quality evidence). There may be no significant difference in toxicity outcomes (RR 1.57, 95% CI 0.85 to 2.92, 2 studies, 764 participants; low-quality evidence) (no data for overall survival were available).The class of small-molecule targeted drugs, BRAF inhibitors (which are active exclusively against BRAF-mutated melanoma), performed better than chemotherapy in terms of overall survival (HR 0.40, 95% CI 0.28 to 0.57, 2 studies, 925 participants; high-quality evidence) and progression-free survival (HR 0.27, 95% CI 0.21 to 0.34, 2 studies, 925 participants; high-quality evidence), and there may be no significant difference in toxicity (RR 1.27, 95% CI 0.48 to 3.33, 2 studies, 408 participants; low-quality evidence).Compared to chemotherapy, MEK inhibitors (which are active exclusively against BRAF-mutated melanoma) may not significantly improve overall survival (HR 0.85, 95% CI 0.58 to 1.25, 3 studies, 496 participants; low-quality evidence), but they probably lead to better progression-free survival (HR 0.58, 95% CI 0.42 to 0.80, 3 studies, 496 participants; moderate-quality evidence). However, MEK inhibitors probably have higher toxicity rates (RR 1.61, 95% CI 1.08 to 2.41, 1 study, 91 participants; moderate-quality evidence).Compared to BRAF inhibitors, the combination of BRAF plus MEK inhibitors was associated with better overall survival (HR 0.70, 95% CI 0.59 to 0.82, 4 studies, 1784 participants; high-quality evidence). BRAF plus MEK inhibitors was also probably better in terms of progression-free survival (HR 0.56, 95% CI 0.44 to 0.71, 4 studies, 1784 participants; moderate-quality evidence), and there appears likely to be no significant difference in toxicity (RR 1.01, 95% CI 0.85 to 1.20, 4 studies, 1774 participants; moderate-quality evidence).Compared to chemotherapy, the combination of chemotherapy plus anti-angiogenic drugs was probably associated with better overall survival (HR 0.60, 95% CI 0.45 to 0.81; moderate-quality evidence) and progression-free survival (HR 0.69, 95% CI 0.52 to 0.92; moderate-quality evidence). There may be no difference in terms of toxicity (RR 0.68, 95% CI 0.09 to 5.32; low-quality evidence). All results for this comparison were based on 324 participants from 2 studies.Network meta-analysis focused on chemotherapy as the common comparator and currently approved treatments for which high- to moderate-quality evidence of efficacy (as represented by treatment effect on progression-free survival) was available (based on the above results) for: biochemotherapy (with both interferon-alpha and interleukin-2); anti-CTLA4 monoclonal antibodies; anti-PD1 monoclonal antibodies; anti-CTLA4 plus anti-PD1 monoclonal antibodies; BRAF inhibitors; MEK inhibitors, and BRAF plus MEK inhibitors. Analysis (which included 19 RCTs and 7632 participants) generated 21 indirect comparisons.The best evidence (moderate-quality evidence) for progression-free survival was found for the following indirect comparisons:• both combinations of immune checkpoint inhibitors (HR 0.30, 95% CI 0.17 to 0.51) and small-molecule targeted drugs (HR 0.17, 95% CI 0.11 to 0.26) probably improved progression-free survival compared to chemotherapy;• both BRAF inhibitors (HR 0.40, 95% CI 0.23 to 0.68) and combinations of small-molecule targeted drugs (HR 0.22, 95% CI 0.12 to 0.39) were probably associated with better progression-free survival compared to anti-CTLA4 monoclonal antibodies;• biochemotherapy (HR 2.81, 95% CI 1.76 to 4.51) probably lead to worse progression-free survival compared to BRAF inhibitors;• the combination of small-molecule targeted drugs probably improved progression-free survival (HR 0.38, 95% CI 0.21 to 0.68) compared to anti-PD1 monoclonal antibodies;• both biochemotherapy (HR 5.05, 95% CI 3.01 to 8.45) and MEK inhibitors (HR 3.16, 95% CI 1.77 to 5.65) were probably associated with worse progression-free survival compared to the combination of small-molecule targeted drugs; and• biochemotherapy was probably associated with worse progression-free survival (HR 2.81, 95% CI 1.54 to 5.11) compared to the combination of immune checkpoint inhibitors.The best evidence (moderate-quality evidence) for toxicity was found for the following indirect comparisons:• combination of immune checkpoint inhibitors (RR 3.49, 95% CI 2.12 to 5.77) probably increased toxicity compared to chemotherapy;• combination of immune checkpoint inhibitors probably increased toxicity (RR 2.50, 95% CI 1.20 to 5.20) compared to BRAF inhibitors;• the combination of immune checkpoint inhibitors probably increased toxicity (RR 3.83, 95% CI 2.59 to 5.68) compared to anti-PD1 monoclonal antibodies; and• biochemotherapy was probably associated with lower toxicity (RR 0.41, 95% CI 0.24 to 0.71) compared to the combination of immune checkpoint inhibitors.Network meta-analysis-based ranking suggested that the combination of BRAF plus MEK inhibitors is the most effective strategy in terms of progression-free survival, whereas anti-PD1 monoclonal antibodies are associated with the lowest toxicity.Overall, the risk of bias of the included trials can be considered as limited. When considering the 122 trials included in this review and the seven types of bias we assessed, we performed 854 evaluations only seven of which (< 1%) assigned high risk to six trials.
AUTHORS' CONCLUSIONS
We found high-quality evidence that many treatments offer better efficacy than chemotherapy, especially recently implemented treatments, such as small-molecule targeted drugs, which are used to treat melanoma with specific gene mutations. Compared with chemotherapy, biochemotherapy (in this case, chemotherapy combined with both interferon-alpha and interleukin-2) and BRAF inhibitors improved progression-free survival; BRAF inhibitors (for BRAF-mutated melanoma) and anti-PD1 monoclonal antibodies improved overall survival. However, there was no difference between polychemotherapy and monochemotherapy in terms of achieving progression-free survival and overall survival. Biochemotherapy did not significantly improve overall survival and has higher toxicity rates compared with chemotherapy.There was some evidence that combined treatments worked better than single treatments: anti-PD1 monoclonal antibodies, alone or with anti-CTLA4, improved progression-free survival compared with anti-CTLA4 monoclonal antibodies alone. Anti-PD1 monoclonal antibodies performed better than anti-CTLA4 monoclonal antibodies in terms of overall survival, and a combination of BRAF plus MEK inhibitors was associated with better overall survival for BRAF-mutated melanoma, compared to BRAF inhibitors alone.The combination of BRAF plus MEK inhibitors (which can only be administered to people with BRAF-mutated melanoma) appeared to be the most effective treatment (based on results for progression-free survival), whereas anti-PD1 monoclonal antibodies appeared to be the least toxic, and most acceptable, treatment.Evidence quality was reduced due to imprecision, between-study heterogeneity, and substandard reporting of trials. Future research should ensure that those diminishing influences are addressed. Clinical areas of future investigation should include the longer-term effect of new therapeutic agents (i.e. immune checkpoint inhibitors and targeted therapies) on overall survival, as well as the combination of drugs used in melanoma treatment; research should also investigate the potential influence of biomarkers.
Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antineoplastic Agents; Brain Neoplasms; CTLA-4 Antigen; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Immunotherapy; Interferon-alpha; Interleukin-2; Male; Melanoma; Middle Aged; Programmed Cell Death 1 Receptor; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Skin Neoplasms
PubMed: 29405038
DOI: 10.1002/14651858.CD011123.pub2 -
Current Issues in Molecular Biology Sep 2022Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no... (Review)
Review
BACKGROUND
Neuroendocrine neoplasms are a heterogeneous group of tumors that raise challenges in terms of diagnosis, treatment and monitoring. Despite continuous efforts, no biomarker has showed satisfying accuracy in predicting outcome or response to treatment.
METHODS
We conducted a systematic review to determine relevant circulating biomarkers for angiogenesis in neuroendocrine tumors. We searched three databases (Pubmed, Embase, Web of Science) using the keywords "neuroendocrine" and "biomarkers", plus specific biomarkers were searched by full and abbreviated name. From a total of 2448 publications, 11 articles met the eligibility criteria.
RESULTS
VEGF is the most potent and the most studied angiogenic molecule, but results were highly controversial. Placental growth factor, Angiopoietin 2 and IL-8 were the most consistent markers in predicting poor outcome and aggressive disease behavior.
CONCLUSIONS
There is no robust evidence so far to sustain the use of angiogenic biomarkers in routine practice, although the results show promising leads.
PubMed: 36135186
DOI: 10.3390/cimb44090274 -
PloS One 2017Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The... (Review)
Review
Metabolomics uses advanced analytical chemistry techniques to comprehensively measure large numbers of small molecule metabolites in cells, tissues and biofluids. The ability to rapidly detect and quantify hundreds or even thousands of metabolites within a single sample is helping scientists paint a far more complete picture of system-wide metabolism and biology. Metabolomics is also allowing researchers to focus on measuring the end-products of complex, hard-to-decipher genetic, epigenetic and environmental interactions. As a result, metabolomics has become an increasingly popular "omics" approach to assist with the robust phenotypic characterization of humans, crop plants and model organisms. Indeed, metabolomics is now routinely used in biomedical, nutritional and crop research. It is also being increasingly used in livestock research and livestock monitoring. The purpose of this systematic review is to quantitatively and objectively summarize the current status of livestock metabolomics and to identify emerging trends, preferred technologies and important gaps in the field. In conducting this review we also critically assessed the applications of livestock metabolomics in key areas such as animal health assessment, disease diagnosis, bioproduct characterization and biomarker discovery for highly desirable economic traits (i.e., feed efficiency, growth potential and milk production). A secondary goal of this critical review was to compile data on the known composition of the livestock metabolome (for 5 of the most common livestock species namely cattle, sheep, goats, horses and pigs). These data have been made available through an open access, comprehensive livestock metabolome database (LMDB, available at http://www.lmdb.ca). The LMDB should enable livestock researchers and producers to conduct more targeted metabolomic studies and to identify where further metabolome coverage is needed.
Topics: Animals; Cattle; Databases, Chemical; Goats; Horses; Internet; Livestock; Metabolome; Metabolomics; Quantitative Trait Loci; Sheep; Swine
PubMed: 28531195
DOI: 10.1371/journal.pone.0177675 -
Frontiers in Physiology 2022Endocannabinoids (eCBS) are endogenously derived lipid signaling molecules that serve as tissue hormones and interact with multiple targets, mostly within the...
Endocannabinoids (eCBS) are endogenously derived lipid signaling molecules that serve as tissue hormones and interact with multiple targets, mostly within the endocannabinoid system (ECS). The ECS is a highly conserved regulatory system involved in homeostatic regulation, organ formation, and immunomodulation of chordates. The term "cannabinoid" evolved from the distinctive class of plant compounds found in , an ancient herb, due to their action on CB1 and CB2 receptors. CB1/2 receptors are the primary targets for eCBs, but their effects are not limited to the ECS. Due to the high interest and extensive research on the ECS, knowledge on its constituents and physiological role is substantial and still growing. Crosstalk and multiple targeting of molecules are common features of endogenous and plant compounds. Cannabimimetic molecules can be divided according to their origin, natural or synthetic, including phytocannabinoids (pCB's) or synthetic cannabinoids (sCB's). The endocannabinoid system (ECS) consists of receptors, transporters, enzymes, and signaling molecules. In this review, we focus on the effects of cannabinoids on Cys-loop receptors. Cys-loop receptors belong to the class of membrane-bound pentameric ligand gated ion channels, each family comprising multiple subunits. Mammalians possess GABA type A receptors (GABAAR), glycine receptors (GlyR), serotonin receptors type 3 (5-HT3R), and nicotinic acetylcholine receptors (nAChR). Several studies have shown different modulatory effects of CBs on multiple members of the Cys-loop receptor family. We highlight the existing knowledge, especially on subunits and protein domains with conserved binding sites for CBs and their possible pharmacological and physiological role in epilepsy and in chronic pain. We further discuss the potential for cannabinoids as first line treatments in epilepsy, chronic pain and other neuropsychiatric conditions, indicated by their polypharmacology and therapeutic profile.
PubMed: 36439263
DOI: 10.3389/fphys.2022.1044575 -
TouchREVIEWS in Endocrinology Nov 2023Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be... (Review)
Review
Pituitary tumours (PTs) are the second most common intracranial tumour. Although the majority show benign behaviour, they may exert aggressive behaviour and can be resistant to treatment. The aim of this review is to report the recently identified biomarkers that might have possible prognostic value. Studies evaluating potentially prognostic biomarkers or a therapeutic target in invasive/recurrent PTs compared with either non-invasive or non-recurrent PTs or normal pituitaries are included in this review. In the 28 included studies, more than 911 PTs were evaluated. A systematic search identified the expression of a number of biomarkers that may be positively correlated with disease recurrence or invasion in PT, grouped according to role: (1) insensitivity to anti-growth signals: minichromosome maintenance protein 7; (2) evasion of the immune system: cyclooxygenase 2, arginase 1, programmed cell death protein 1 (PD-1)/programmed death ligand 2, cluster of differentiation (CD) 80/CD86; (3) sustained angiogenesis: endothelial cell-specific molecule, fibroblast growth factor receptor, matrix metalloproteinase 9, pituitary tumour transforming gene; (4) self-sufficiency in growth signals: epidermal growth factor receptor; and (5) tissue invasion: matrix metalloproteinase 9, fascin protein. Biomarkers with a negative correlation with disease recurrence or invasion include: (1) insensitivity to anti-growth signals: transforming growth factor β1, Smad proteins; (2) sustained angiogenesis: tissue inhibitor of metalloproteinase 1; (3) tissue invasion: Wnt inhibitory factor 1; and (4) miscellaneous: co-expression of glial fibrillary acidic protein and cytokeratin, and oestrogen receptors α36 and α66. PD-1/programmed cell death ligand 1 showed no clear association with invasion or recurrence, while cyclin A, cytotoxic T lymphocyte-associated protein 4, S100 protein, ephrin receptor, galectin-3 , neural cell adhesion molecule, protein tyrosine phosphatase 4A3 and steroidogenic factor 1 had no association with invasion or recurrence of PT. With the aim to develop a more personalized approach to the treatment of PT, and because of the limited number of molecular targets currently studied in the context of recurrent PT and invasion, a better understanding of the most relevant of these biomarkers by well-d esigned interventional studies will lead to a better understanding of the molecular profile of PT. This should also meet the increased need of treatable molecular targets.
PubMed: 38187082
DOI: 10.17925/EE.2023.19.2.12 -
Clinical Medicine & Research Dec 2023Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant... (Review)
Review
Lichen planus (LP) is a chronic autoimmune disease of skin and mucous membranes. World Health Organization has announced oral lichen planus (OLP) as a premalignant lesion. The exact etiology of OLP remains unknown; however, different mechanisms may be involved in its immunopathogenesis. The upregulation of cytokines, chemokines, and adhesion molecules is consistent with a persistent and erratic immunological response to OLP-mediated antigens generated by oral keratinocytes and innate immune cells. These molecules attract T cells, and mast cells to the disease site and regulate complex interactions among cells that lead to death of keratinocytes, degradation of basement membrane, and chronicity of the disease. It is believed that CD8+ and CD4+ T helper 1 (Th1) cells are the main lymphocytes involved in this process, although recent evidence suggests implication of other T helper subgroups, such as Th23, Th17, and regulatory T cells (Tregs), proposing a more complex cellular immunity process to be involved in its pathogenesis. The emphasis of this research review is on the function of IL-17 in the pathophysiology of OLP and how current discoveries may point to future treatment strategies. This research protocol will follow Preferred Reporting Items for Systematic Reviews (PRISMA 2020) checklist. An electronic search was conducted in PubMed, Scopus, Google Scholar, Embase, and Cochrane databases for articles published from 1960 to June 2022. Based on the eligibility criteria, 21 articles were enrolled. In comparison to healthy controls, the findings of this review demonstrated greater expression of IL-17 and Th-17 in the blood, saliva, and tissues of OLP and LP patients. Additionally, there was a strong link between the relative levels of IL-17 and IL-23 expression. Treatment with monoclonal antibodies against Th-17/Tc-17, IL-12/IL-23, and IL-23 would result in significant long-term improvement of LP symptoms.
Topics: Humans; Lichen Planus, Oral; Interleukin-17; Cytokines; Lichen Planus; Interleukin-23
PubMed: 38296640
DOI: 10.3121/cmr.2023.1822 -
Osteoarthritis and Cartilage Apr 2019To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass spectroscopy (MS) analysis...
OBJECTIVE
To perform a systematic review of the small molecule metabolism studies of osteoarthritis utilising nuclear magnetic resonance (NMR) or mass spectroscopy (MS) analysis (viz., metabolomics or metabonomics), thereby providing coherent conclusions and reference material for future study.
METHOD
We applied PRISMA guidelines (PROSPERO 95068) with the following MESH terms: 1. "osteoarthritis" AND ("metabolic" OR "metabonomic" OR "metabolomic" OR "metabolism") 2. ("synovial fluid" OR "cartilage" OR "synovium" OR "serum" OR "plasma" OR "urine") AND ("NMR" or "Mass Spectroscopy"). Databases searched were "Medline" and "Embase". Studies were searched in English and excluded review articles not containing original research. Study outcomes were significant or notable metabolites, species (human or animal) and the Newcastle-Ottawa Score.
RESULTS
In the 27 studies meeting the inclusion criteria, there was a shift towards anaerobic and fatty acid metabolism in OA disease, although whether this represents the inflammatory state remains unclear. Lipid structure and composition was altered within disease subclasses including phosphatidyl choline (PC) and the sphingomyelins. Macromolecular proteoglycan destruction was described, but the correlation to disease factors was not demonstrated. Collated results suggested arachidonate signalling pathways and androgen sex hormones as future metabolic pathways for investigation.
CONCLUSION
Our meta-analysis demonstrates significant small molecule differences between sample types, between species (such as human and bovine), with potential OA biomarkers and targets for local or systemic therapies. Studies were limited by numbers and a lack of disease correlation. Future studies should use NMR and MS analysis to further investigate large population subgroups including inflammatory arthropathy, OA subclasses, age and joint differences.
Topics: Animals; Biomarkers; Cartilage; Humans; Magnetic Resonance Spectroscopy; Mass Spectrometry; Metabolomics; Osteoarthritis; Synovial Membrane
PubMed: 30287397
DOI: 10.1016/j.joca.2018.08.024 -
Frontiers in Medicine 2022Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved...
INTRODUCTION
Pruritus is a major and burdensome symptom in atopic dermatitis (AD). The number of systemic treatments available for AD has increased recently, enabling improved patient relief.
OBJECTIVE
To evaluate the effect of AD treatments on pruritus.
METHODS
A systematic literature review and a meta-analysis were conducted to evaluate and compare the effects of treatment used in AD on pruritus. PubMed and Embase databases were searched to find articles published between January 1990 and December 2021. Topical and systemic treatments were studied in patients aged ≥10 years.
RESULTS
Among the 448 articles identified, 56 studies were retained in the systematic review. A total of 15 studies evaluated topical treatments: topical corticosteroids (TCS; 2), calcineurin inhibitors (6), PDE4 inhibitors (3), and Jak inhibitors (4). A total of five studies were included in the meta- analysis. All treatments had a positive effect on pruritus, with a mean overall reduction of 3.32/10, 95% IC [2.32-4.33]. The greatest reduction was observed with halometasone (mean: 4.75), followed by tofacitinib 2% (mean: 4.38). A total of 41 studies evaluated systemic therapies: cyclosporine (6), phototherapy (5), azathioprine (2), dupilumab (9), anti-IL 13 (5), nemolizumab (3), Jak inhibitors (9), mepolizumab (1), and apremilast (1). A total of 17 studies were included in 2 meta-analyses according to the concomitant use or not of TCS. In the meta-analysis without TCS, the overall decrease was 3.07/10, 95% IC [2.58-3.56]. The molecules with the highest efficacy on pruritus were upadacitinib 30 mg (mean: 4.90) and nemolizumab (mean: 4.81).
DISCUSSION
The therapeutic arsenal for AD has increased rapidly, and many molecules are under development. The primary endpoint of clinical trials is most often a score that assesses the severity of AD; however, the assessment of pruritus is also essential. The majority of molecules have a positive effect on pruritus, but the improvement varies between them. Efficacy on pruritus is not always correlated with efficacy on AD lesions; therefore, these two criteria are crucial to evaluate. The limitations of this study were the heterogeneity in the assessment of pruritus, the moment of the assessment, and the concomitant application of TCS or not for studies evaluating systemics. In the future, it would be useful to use standardized criteria for assessing pruritus.
PubMed: 36619624
DOI: 10.3389/fmed.2022.1079323 -
European Review For Medical and... Jul 2023The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs.... (Meta-Analysis)
Meta-Analysis
The comparative efficacy and safety of biologics and small molecules for treating patients with ulcerative colitis in Portugal: a systematic literature review and network meta-analysis.
OBJECTIVE
The use of biological drugs to treat ulcerative colitis (UC) represents a clear added value; nevertheless, many patients do not have a sustained response to these drugs. Small molecules were recently approved for the treatment of UC in Portugal. This network meta-analysis aimed to compare the efficacy and safety of the different therapies, including biological and small molecules, in patients prior exposed to biological treatment.
MATERIALS AND METHODS
A systematic review of the literature was performed on January 6, 2022, identifying all the relevant reports about the efficacy and safety of biologics (adalimumab, golimumab, infliximab, vedolizumab, ustekinumab) and small molecules (upadacitinib, filgotinib, tofacitinib) in the treatment of UC in Portugal. Network meta-analysis (NMA) was conducted using Bayesian Markov Chain Monte Carlo simulations. Results were presented in median Odds Ratio and Surface Under the Cumulative RAnking (SUCRA) score for each treatment.
RESULTS
Treatment of UC is divided into two phases: induction and maintenance. Upadacitinib 45 mg was the most efficacious therapy in achieving clinical remission and response and endoscopic improvement in the induction phase. Concerning the maintenance phase, upadacitinib 30 mg performed better than ustekinumab formulations in clinical remission and response, and endoscopic improvement. Regarding safety, there were no significant differences between all the drugs included in the analysis.
CONCLUSIONS
This network meta-analysis showed that upadacitinib reflects better efficacy compared to the available treatments for bio-exposed patients with moderate to severe UC. The safety profile is comparable to the other drugs.
Topics: Humans; Colitis, Ulcerative; Ustekinumab; Network Meta-Analysis; Portugal; Bayes Theorem; Biological Factors; Biological Products
PubMed: 37522686
DOI: 10.26355/eurrev_202307_33145