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Medicine Dec 2023A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth... (Meta-Analysis)
Meta-Analysis
Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials.
INTRODUCTION
A systematic review and meta-analysis were conducted to evaluate the efficacy and the overall safety of Faricimab compared with other anti-vascular endothelial growth factors (VEGF) therapy for neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME).
MATERIALS AND METHODS
A systematic literature search of a comprehensive electronic database was performed to identify randomized clinical trials published from January 2013 to January 2023 for Faricimab in AMD and DME. Weighted mean differences and risk ratios were used to integrate the different studies.
RESULTS
A total of 4 randomized controlled trials (RCTs) with 1678 AMD patients and 3 RCTs with 20 DME patients were included in the meta-analysis.In patients with AMD, a significant difference was found in the number of injections between Faricimab and other anti-VEGF therapy (MD = -2.42, 95% CI [-3.93 to -0.90], P = .002).No significant difference was found for the change in best corrected visual acuity (BVCA), central subfoveal thickness (CST), and gaining 15 or more letters. Similarly, no significant difference was found for adverse events.In patients with DME, a significant difference was observed for CST (MD = -22.41, 95% CI [-29.95 to -14.86], P < .00001) and the number of injections(MD = -0.93, 95% CI [-1.33 to -0.54], P < .00001). No significant difference was found for BVCA and gaining 15 or more letters, and no significant difference was found for adverse events.
CONCLUSIONS
Comprehensive evidence confirms that Faricimab achieves non-inferior or even better CST improvement than other anti-VEGF therapies with extended dosing intervals, but more long-term follow-up studies are needed to support our conclusions.
Topics: Antibodies, Bispecific; Vascular Endothelial Growth Factor A; Macular Degeneration; Humans; Randomized Controlled Trials as Topic; Macular Edema; Diabetes Complications; Treatment Outcome
PubMed: 38115358
DOI: 10.1097/MD.0000000000036370 -
Journal of Hematology & Oncology Oct 2016Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been... (Meta-Analysis)
Meta-Analysis Review
Monoclonal antibodies and small molecule tyrosine kinase inhibitors (TKIs) directed against the vascular endothelial growth factor (VEGF) or its receptors have been investigated in several studies for the treatment of advanced gastric cancer (GC). In the present study, we aimed to evaluate the efficacy and safety of angiogenesis inhibitors in advanced GC. We searched published randomized controlled trials (RCTs) comparing angiogenesis inhibitors with non-angiogenesis inhibitors for the treatment of GC. MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched. The extracted data on progression-free survival (PFS) and overall survival (OS) were measured in terms of hazard ratios (HR) and corresponding 95 % confidence intervals (CIs). In addition, risk ratios (RR) and corresponding 95 % CIs were pooled for objective response rate (ORR), disease control rate (DCR), and risk of adverse events (AEs). Ten RCTs involving 2786 patients were included. Compared with non-angiogenesis inhibitor-containing regimens, angiogenesis inhibitor-containing regimens resulted in a significant improvement in OS (HR 0.80, 95 % CI 0.69-0.93, P = 0.004), prolonged PFS (HR 0.66, 95 % CI 0.51-0.86, P = 0.002), and superior ORR (RR 1.34, 95 % CI 1.09-1.65, P = 0.005) and DCR (RR 1.37, 95 % CI 1.17-1.61, P = 0.0001). Angiogenesis inhibitors were associated with a greater number of AEs, but most of these were predictable and manageable. However, hand-foot syndrome, diarrhea, and gastrointestinal (GI) perforation were significantly increased in patients treated with angiogenesis inhibitors. In summary, angiogenesis inhibitor-containing regimens were superior to non-angiogenesis inhibitor-containing regimens in terms of OS, PFS, RR, and DCR in patients with advanced GC.
Topics: Angiogenesis Inhibitors; Disease-Free Survival; Humans; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Treatment Outcome
PubMed: 27756337
DOI: 10.1186/s13045-016-0340-8 -
Frontiers in Immunology 2023The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term... (Meta-Analysis)
Meta-Analysis
Short-term risk and long-term incidence rate of infection and malignancy with IL-17 and IL-23 inhibitors in adult patients with psoriasis and psoriatic arthritis: a systematic review and meta-analysis.
UNLABELLED
The risk of infection and malignancy may be a concern for patients with psoriasis receiving interleukin (IL)-17 and IL-23 inhibitors, particularly with long-term treatments. We aimed to estimate the short-term risks and long-term incidence rates of infection and malignancy with IL-17 or IL-23 antagonists in adult patients with psoriasis and psoriatic arthritis through this comprehensive meta-analysis (PROSPERO registration number: CRD42022363127). We searched PubMed, MEDLINE, Web of Science and ClinicalTrials.gov until May 17, 2023 for randomized placebo-controlled trials and long-term (≥ 52 weeks) open-label extension studies. The estimates of short-term risk ratios (RRs) and long-term exposure-adjusted incidence rates (EAIRs) were pooled using R software 4.1.1 and STATA 16.0. This review included 45 randomized placebo-controlled studies and 27 open-label extension studies. Short-term RRs of serious infection, overall infection and malignancy were 1.45 (95% confidence intervals, 95% CI: 0.81-2.59), 1.20 (95% CI: 1.06-1.35), 0.83 (95% CI: 0.41-1.71) with IL-17 inhibitors; and 0.68 (95% CI: 0.38-1.22), 1.13 (95% CI: 1.00-1.28), 0.87 (95% CI: 0.37-2.04) with IL-23 inhibitors. Increased short-term risks of nasopharyngitis and infection with IL-17 inhibitors were found. Long-term EAIRs of serious infection, overall infection, nonmelanoma skin cancer (NMSC), malignancies excluding NMSC, nasopharyngitis and upper respiratory tract infection were 1.11/100 patient-years (PYs), 57.78/100PYs, 0.47/100PYs, 0.24/100PYs, 15.07/100PYs, 8.52/100PYs, 3.41/100PYs with IL-17 inhibitors; and 1.09/100PYs, 48.50/100PYs, 0.40/100PYs, 0.43/100PYs, 10.75/100PYs, 5.84/100PYs with IL-23 inhibitors. Long-term EAIR of infection was 3.41/100PYs with IL-17 inhibitors. No active or reactivated tuberculosis was ever reported in all the trials, and only a few cases of latent tuberculosis, hepatitis, and herpes zoster were reported during the long-term extension periods. No evidence of increased EAIRs of infection and malignancy with longer durations was found. Our study suggested that short-term risk and long-term incidence of infections and malignancies in psoriasis patients receiving IL-17 inhibitors and IL-23 inhibitors are generally low. However, close monitoring is required for nasopharyngitis and infection with IL-17 inhibitors.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022363127.
Topics: Adult; Humans; Arthritis, Psoriatic; Candidiasis; Incidence; Interleukin Inhibitors; Interleukin-17; Interleukin-23; Nasopharyngitis; Neoplasms; Psoriasis
PubMed: 38106423
DOI: 10.3389/fimmu.2023.1294416 -
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 -
BMJ Open Aug 2023To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to reduce MVCs.
DESIGN
Medline (Ovid), EMBASE and Global Health electronic databases were systematically searched from inception to March 2022 for observational and interventional English-language studies. Screening, data extraction and appraisals using the Joanna Briggs Institute appraisal tools were completed by two reviewers independently. Where appropriate, measures of association were converted into risk ratios (RRs) or ORs for meta-analysis.
PARTICIPANTS
Drivers of four-wheeled vehicles of all ages with no cognitive declines.
PRIMARY AND SECONDARY OUTCOMES
MVC involvement (primary) and driving cessation (secondary).
RESULTS
101 studies (n=778 052) were included after full-text review. 57 studies only involved older drivers (≥65 years) and 85 were in high-income settings. Heterogeneity in the data meant that most meta-analyses were underpowered as only 25 studies, further split into different groups of eye diseases and measures of vision, could be meta-analysed. The limited evidence from the meta-analyses suggests that visual field defects (four studies; RR 1.51 (95% CI 1.23, 1.85); p<0.001; I=46.79%), and contrast sensitivity (two studies; RR 1.40 (95% CI 1.08, 1.80); p=0.01, I=0.11%) and visual acuity loss (five studies; RR 1.21 (95% CI 1.02, 1.43); p=0.03, I=28.49%) may increase crash risk. The results are more inconclusive for available evidence for associations of glaucoma (five studies, RR 1.27 (95% CI 0.67, 2.42); p=0.47; I=93.48%) and cataract (two studies RR 1.15 (95% CI 0.97, 1.36); p=0.11; I=3.96%) with crashes. Driving cessation may also be linked with glaucoma (two studies; RR 1.62 (95% CI 1.20, 2.19); p<0.001, I=22.45%), age-related macular degeneration (AMD) (three studies; RR 2.21 (95% CI 1.47, 3.31); p<0.001, I=75.11%) and reduced contrast sensitivity (three studies; RR 1.30 (95% CI 1.05, 1.61); p=0.02; I=63.19%). Cataract surgery halved MVC risk (three studies; RR 0.55 (95% CI 0.34, 0.92); p=0.02; I=97.10). Ranibizumab injections (four randomised controlled trials) prolonged driving in persons with AMD.
CONCLUSION
Impaired vision identified through a variety of measures is associated with both increased MVC involvement and cessation. Cataract surgery can reduce MVC risk. Despite literature being highly heterogeneous, this review shows that detection of vision problems and appropriate treatment are critical to road safety.
PROSPERO REGISTRATION NUMBER
CRD42020172153.
Topics: Humans; Visual Acuity; Ranibizumab; Accidents, Traffic; Macular Degeneration; Vision Disorders; Cataract
PubMed: 37567751
DOI: 10.1136/bmjopen-2022-065210 -
Dermatology (Basel, Switzerland) 2022Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood,... (Review)
Review
BACKGROUND
Chronic nodular prurigo (CNPG) is a chronic, inflammatory skin disease, characterized by intense and debilitating pruritus. The pathophysiology is not fully understood, and the condition is difficult to treat with no targeted therapies. The aim of this systematic review was to review the evidence of therapies for non-atopic CNPG and conduct a meta-analysis of the results.
SUMMARY
We conducted a systematic review of the literature concerning effect of treatment for non-atopic CNPG. Due to few randomized controlled trials (RCTs) and case series, the literature was unfortunately too sparse to conduct a meta-analysis of the results. Instead, we thoroughly report important data from the three existing RCTs and 6 case studies with more than 15 patients. Evaluated therapies include nemolizumab, aprepitant, topical therapy with hydrocortisone and pimecrolimus, thalidomide, UVA phototherapy, pregabalin, and naltrexone. Included RCTs and case studies all had a heterogeneous methodology making direct comparison almost impossible.
KEY MESSAGES
There is sparse evidence for the currently used therapies for non-atopic CNPG. Several RCTs on new therapies are running or in the pipeline, hopefully providing new, effective, and targeted treatment possibilities for CNPG patients both with and without an atopic predisposition.
Topics: Chronic Disease; Graft vs Host Disease; Humans; Hypersensitivity, Immediate; Prurigo; Pruritus; Skin; Thalidomide; Ultraviolet Therapy
PubMed: 35417906
DOI: 10.1159/000523700 -
OncoTargets and Therapy 2018With the investigation of molecular targets, many agents, such as trastuzumab and ramucirumab, have attained a positive outcome in oncotherapy. Vascular endothelial... (Review)
Review
With the investigation of molecular targets, many agents, such as trastuzumab and ramucirumab, have attained a positive outcome in oncotherapy. Vascular endothelial growth factor (VEGF) is considered a potent factor in angiogenesis and plays an important role in the growth of tumors. Moreover, both VEGF and its receptor are usually excessively expressed in solid tumors and could be hopeful targets for the treatment of neoplasms. Apatinib (YN968D1) is an oral small-molecule tyrosine kinase inhibitor of VEGFR-2. By inhibiting several signaling transduction pathways, it restrains angiogenesis and subsequently controls tumorigenesis. According to current studies, apatinib shows promising application in various solid tumors as a post-second- and post-third-line treatment. It could significantly improve the median overall survival and progression-free survival of patients with tolerated adverse reactions. This paper aims to summarize the recent research on apatinib including the mechanism, pharmacokinetics, trials, adverse reactions, and prospect as a treatment.
PubMed: 30050305
DOI: 10.2147/OTT.S172305 -
Drugs May 2024The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
The most recently approved biologics for moderate-to-severe psoriasis are the interleukin (IL)-17 and IL-23 inhibitors. Drug survival is a frequently used outcome to assess drug performance in practice. An overview of the available drug survival studies regarding IL-17 and IL-23 inhibitors is lacking. Therefore, our objective was to assess the drug survival of IL-17 and IL-23 inhibitors for psoriasis.
METHODS
A search of PubMed, Embase, Cochrane Library and Web of Science was conducted (last search 27 December, 2023). Inclusion criteria were (1) cohort study; (2) patients aged ≥ 18 years with plaque psoriasis; and (3) evaluation of drug survival of at least one of the IL-17 and IL-23 inhibitors. Exclusion criteria were: primary focus on patients with psoriatic arthritis, fewer than ten study subjects and another language than English. The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was followed. Survival probabilities at monthly intervals were extracted from Kaplan-Meier curves using a semi-automated tool. Data were pooled using a non-parametric random-effects model to retrieve distribution-free summary survival curves. Summary drug survival curves were constructed per biologic for different discontinuation reasons: overall, ineffectiveness and adverse events, and split for the effect modifier biologic naivety. Results were analysed separately for registry/electronic health record data and for pharmacy/claims data.
RESULTS
A total of 69 studies aggregating drug survival outcomes of 48,704 patients on secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, and tildrakizumab were included. Summary drug survival estimates of registry/electronic health record studies for overall, ineffectiveness and adverse event related drug survival were high (all point estimates ≥ 0.8 at year 1) for included biologics, with highest estimates for guselkumab and risankizumab. All estimates for drug survival were higher in biologic naive than in experienced patients. Estimates of pharmacy/claims databases were substantially lower than estimates from the primary analyses based on registry/electronic health record data.
CONCLUSIONS
This meta-analysis showed that the investigated IL-17 and IL-23 inhibitors had high drug survival rates, with highest rates for guselkumab and risankizumab drug survival. We showed that effect modifiers such as biologic naivety, and the source of data used (registry/electronic health record data vs pharmacy/claims databases) is relevant when interpreting drug survival studies.
Topics: Humans; Psoriasis; Interleukin-17; Interleukin-23; Antibodies, Monoclonal, Humanized; Dermatologic Agents
PubMed: 38630365
DOI: 10.1007/s40265-024-02028-1 -
Alimentary Pharmacology & Therapeutics Jun 2015It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD). (Review)
Review
BACKGROUND
It has been reported that thalidomide may be effective in treating inflammatory bowel disease (IBD).
AIM
To review the evidence examining the efficacy and safety of thalidomide for inducing and maintaining remission in Crohn's disease (CD) and ulcerative colitis (UC).
METHODS
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed (1950-August 2014), EMBASE (1984-August 2014), Scopus, and Web of knowledge were searched for randomised controlled trials (RCTs), observational studies and case series. The primary outcomes were induction of remission or response for active IBD or relapse rate for patients in remission and subsequently on thalidomide/analogues for at least 3 months.
RESULTS
Twelve studies (2 RCTs and 10 case series) met the inclusion criteria for inducing remission and included 248 patients (10 with UC, 238 with CD). Only one RCT of paediatric CD achieved high quality scores (remission rate thalidomide: 46%, placebo: 12%; p=0.01). The crude pooled remission rate for thalidomide was 49% and 25% in luminal and perianal CD respectively. For UC, 50% achieved remission and 10% had partial response. One case series reported 21 patients (17 CD, four UC) who maintained remission for 6 months. Many adverse events were reported including sedation (32%) and peripheral neuropathy (20%).
CONCLUSIONS
One high quality RCT showed that thalidomide is effective for inducing remission in paediatric CD. The current evidence is insufficient to support using thalidomide to induce remission in UC or adult CD, or to maintain remission in IBD. Significant adverse events may occur, necessitating discontinuation of thalidomide.
Topics: Adult; Child; Colitis, Ulcerative; Crohn Disease; Humans; Inflammatory Bowel Diseases; Remission Induction; Thalidomide
PubMed: 25858208
DOI: 10.1111/apt.13181 -
The Oncologist Feb 2015Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect.... (Review)
Review
Bevacizumab, currently an option for treatment of different types of tumors including glioblastoma, has a peculiar toxicity profile related to its antiangiogenic effect. Because some bevacizumab-related adverse events can be life threatening, it is important to identify risk factors and to establish treatment protocols to minimize treatment-related morbidity and mortality. In glioblastoma patients, the risk of developing certain side effects, such as gastrointestinal perforation, venous thromboembolism, and intracranial hemorrhages, is slightly higher than in patients treated with bevacizumab for other tumor types. We performed a systematic review of the side effects of bevacizumab and their incidence, causal mechanisms, and available treatments. Finally, we identified risk factors and proposed preventive and therapeutic measures for these adverse events.
Topics: Angiogenesis Inhibitors; Bevacizumab; Disease Management; Glioblastoma; Humans; Venous Thromboembolism
PubMed: 25568148
DOI: 10.1634/theoncologist.2014-0330