Pharmacological treatments for neovascular age-related macular degeneration: can mixed treatment comparison meta-analysis be useful?

Abstract:

OBJECTIVE:To investigated the use of mixed treatment comparison (MTC) meta-analysis models to summarize results from randomized clinical trials (RCTs) on approved pharmacological treatments for neovascular age-related macular degeneration (AMD). METHODS:The number of patients with visual loss or visual gain of 3 or more lines of visual acuity (15 ETDRS letters) at 1 year was extracted from 10 RCTs including patients with neovascular AMD and comparing at least one of the following drugs to sham treatment (1080 control patients, 8 studies) or to each other: verteporfin photodynamic therapy (PDT, 1124 patients, 4 studies), pegaptanib (904 patients, 2 twin studies), ranibizumab (984 patients, 4 studies). Both frequentist and Bayesian methods were used to conduct MTCs. RESULTS:Direct and indirect evidence was available and found to be overall in good agreement for the comparisons: PDT vs. control, ranibizumab vs. control, ranibizumab vs. PDT. Bayesian model fit was better for a model including a covariate coding for the PIER study ranibizumab regimen, i.e. quarterly injections after three initial monthly doses. In the MTC model, monthly ranibizumab was superior to PDT and pegaptanib, and could not be shown to be better than PIER ranibizumab regarding visual loss, being estimates imprecise. Ranibizumab PIER retreatment regimen was better than PDT and pegaptanib regarding visual loss, whereas an advantage over them regarding visual gain was suggested by a frequentist MTC approach, but not by a Bayesian approach, which was more conservative. A limitation of our MTC model was that only two twin studies connected pegaptanib to the treatment network, and only one study was available for the PIER ranibizumab regimen. CONCLUSION:The clinically heterogeneous and sparse typology of the evidence is a limitation to carry out MTC meta-analyses of approved pharmacological treatments for neovascular AMD. Ranibizumab was found to be the most effective treatment compared to PDT and pegaptanib, although this superiority cannot be demonstrated regarding visual gain for the PIER ranibizumab regimen in a Bayesian analytic setting. We did not find RCTs which investigated the current ranibizumab as needed retreatment regimen approved in Europe.

journal_name

Curr Drug Targets

journal_title

Current drug targets

authors

Virgili G,Novielli N,Menchini F,Murro V,Giacomelli G

doi

10.2174/138945011794182665

subject

Has Abstract

pub_date

2011-02-01 00:00:00

pages

212-20

issue

2

eissn

1389-4501

issn

1873-5592

pii

BSP/CDT/E-Pub/00178

journal_volume

12

pub_type

杂志文章,meta分析,评审
  • Diacylglycerol kinases as emerging potential drug targets for a variety of diseases.

    abstract::Diacylglycerol (DAG) kinase (DGK) modulates the balance between the two signaling lipids, DAG and phosphatidic acid (PA), by phosphorylating (consuming) DAG to yield PA. Ten mammalian DGK isozymes have been identified to date. In addition to two or three cysteine-rich C1 domains (protein kinase C-like zinc finger stru...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008785132394

    authors: Sakane F,Imai S,Kai M,Yasuda S,Kanoh H

    更新日期:2008-08-01 00:00:00

  • Drug Development Strategy for Type 2 Diabetes: Targeting Positive Energy Balances.

    abstract::Newer classes of medications have been proven useful in glycemic control in type 2 diabetes (T2D), but many do not appear capable to slow down the progressive loss of ß-cell function, or to improve population-level glycemic control. Positive energy balance, e.g. surplus energy intake over expenditure, is at the core f...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666181217111500

    authors: Liu Z,Yang B

    更新日期:2019-01-01 00:00:00

  • Targeting the RAS signaling pathway in malignant hematologic diseases.

    abstract::Molecularly targeting signaling pathways that are involved in the pathogenesis of hematopoietic malignancies may lead to more specific and efficacious therapies. Activation of the RAS signal transduction cascade is a common feature in the molecular pathogenesis of hematologic malignancies. A number of novel agents tar...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007779940043

    authors: Morgan MA,Ganser A,Reuter CW

    更新日期:2007-02-01 00:00:00

  • Targeting plasminogen activator inhibitor-1: role in cell signaling and the biology of domain-specific knock-in mice.

    abstract::It is well documented that elevated levels of PAI-1 in plasma can decrease the fibrinolytic activity in blood with an associated increased risk of thrombus formation. A diverse range of molecules including bacterial lipopolysaccharide (LPS), the inflammatory mediators tumor necrosis factor alpha (TNFalpha) and interle...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007781662382

    authors: Balsara RD,Xu Z,Ploplis VA

    更新日期:2007-09-01 00:00:00

  • Saponins as tool for improved targeted tumor therapies.

    abstract::Saponins are plant glycosides that consist of a steroid, steroid alkaloid or triterpenoid aglycone and one or more sugar chains that are covalently linked by glycosidic binding to the aglycone. Glucose, galactose, glucuronic acid, xylose and rhamnose are commonly bound monosaccharides. Saponins are found in all organs...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945009787354584

    authors: Fuchs H,Bachran D,Panjideh H,Schellmann N,Weng A,Melzig MF,Sutherland M,Bachran C

    更新日期:2009-02-01 00:00:00

  • Epigenetic Therapies and Potential Drugs for Treating Human Cancer.

    abstract::Epigenetic modifications ensure the maintenance of normal cellular functions, and their dysregulation is frequently found in many disease states, including cancer. Nowadays, the most studied epigenetic dysregulation associated with tumorigenesis, cancer progression and metastasis refers to the variations in DNA methyl...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121666200325093104

    authors: Lin SQ,Li X

    更新日期:2020-01-01 00:00:00

  • Study of Monocytes/Macrophages Stimuli as the Targets of Treating Inflammatory Bone Diseases.

    abstract::Inflammation is the most common pathology in many orthopedic diseases, such as: rheumatoid arthritis (RA), osteoarthritis (OA) and other reasons caused osteolysis. The leading factor of inflammation was considered as the differentiation of monocyte and the polarization of macrophage. However, cytokines and different c...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450120666191015211737

    authors: Liu Y,Cao Y,Smith W,He B,Yan L

    更新日期:2020-01-01 00:00:00

  • Endogenous Enzyme-responsive Nanoplatforms for Anti-tumor Therapy.

    abstract::The emergency of responsive drug delivery systems has contributed to the reduced cytotoxicity, the improved permeability in tissues and extended circulation time of the active drug. Of particular, enzyme-responsive nanoplatforms have attracted a lot due to the specificity and efficiency of an enzyme-catalyzed reaction...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450122666210114095614

    authors: Lou XF,Du YZ,Xu XL

    更新日期:2021-01-13 00:00:00

  • Myocardial infarction following atherosclerosis in murine models.

    abstract::The most widely used mouse models for atherosclerosis are LDL receptor knockout (KO) mice and apolipoprotein E (apoE) KO mice fed standard chow diets or lipid-supplemented diets. Unfortunately, these do not usually exhibit myocardial infarction or other features of human cardiovascular disease such as occlusive corona...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008783755566

    authors: Braun A,Rigotti A,Trigatti BL

    更新日期:2008-03-01 00:00:00

  • Novel targeted therapies to overcome trastuzumab resistance in HER2-overexpressing metastatic breast cancer.

    abstract::Overexpression of the human epidermal growth factor receptor 2 (HER2) is identified in approximately 25- 30% of breast cancers and indicates a poor prognosis. Trastuzumab, the anti-HER2 monoclonal antibody (mAb), has shown significant clinical effects selectively in HER2-overexpressing metastatic breast cancer (MBC) w...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/13894501113149990161

    authors: Huang Y,Fu P,Fan W

    更新日期:2013-07-01 00:00:00

  • Transcriptional Regulation of mPGES1 in Cancer: An Alternative Approach to Drug Discovery?

    abstract::Prostaglandins serve as the connecting link between inflammation and cancer. mPGES1, the downstream enzyme in the prostaglandin pathway is considered a better target than COX-2 against the progression of cancer due to the cardiovascular and other complications associated with the inhibition of the latter. Despite the ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160826093137

    authors: Ramanan M,Doble M

    更新日期:2017-01-01 00:00:00

  • The therapeutic value of natural agents to treat miRNA targeted breast cancer in African-American and Caucasian-American women.

    abstract::Breast cancer is the most common cancer in women in the United States, with African-American (AA) women showing significantly higher rates than Caucasian-American (CA) women do. The reason for this racial disparity remains unknown, and factors that might be responsible for the differences in incidence and mortality ha...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945012804545461

    authors: Rahman KM,Sakr WA

    更新日期:2012-12-01 00:00:00

  • The toll of Toll-like receptors, especially toll-like receptor 2, on murine atherosclerosis.

    abstract::At one time, atherosclerosis was thought to be a simple lipid storage disease. However, it is now recognized as a chronic and progressive inflammation of the arterial wall. Gene deletion experiments in murine models of atherosclerosis that reduce the inflammatory process also reduce disease severity. Identifying the i...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007783220605

    authors: Curtiss LK,Tobias PS

    更新日期:2007-12-01 00:00:00

  • Subunit characterization of NMDA receptors.

    abstract::NMDA receptors are a subclass of excitatory, ionotropic L-glutamate neurotransmitter receptors. They are.heteromeric, integral membrane proteins being formed by the assembly of the obligatory NR1 subunit together with modulatory NR2 subunits of which four different types, NR2A-NR2D, have been described. This results i...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450013348461

    authors: Stephenson FA

    更新日期:2001-09-01 00:00:00

  • PD-L1 Testing for Urothelial Carcinoma: Interchangeability, Reliability and Future Perspectives.

    abstract::Five programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors are currently approved for the treatment of locally advanced or metastatic urothelial carcinoma of the bladder and the upper urinary tract. Following the FDA and EMA restrictions of first-line treatment with Atezolizumab and Pembrolizumab in platinum...

    journal_title:Current drug targets

    pub_type: 杂志文章

    doi:10.2174/1389450121666200510015216

    authors: Gevaert T,Cimadamore A,Montironi R,Eckstein M

    更新日期:2020-05-09 00:00:00

  • The AcrB efflux pump: conformational cycling and peristalsis lead to multidrug resistance.

    abstract::Antimicrobial resistance of human pathogenic bacteria is an emerging problem for global public health. This resistance is often associated with the overproduction of membrane transport proteins that are capable to pump chemotherapeutics, antibiotics, detergents, dyes and organic solvents out of the cell. In Gram-negat...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945008785747789

    authors: Seeger MA,Diederichs K,Eicher T,Brandstätter L,Schiefner A,Verrey F,Pos KM

    更新日期:2008-09-01 00:00:00

  • Intrathecal rituximab therapy in multiple sclerosis: review of evidence supporting the need for future trials.

    abstract::Rituximab has demonstrated a major effect in B-cell lymphoma and in a wide range of autoimmune disorders. Unfortunately, the blood-brain-barrier excludes the disorders restricted to the central nervous system (CNS) from the action of rituximab. The progressive phase of multiple sclerosis (MS) is a prototypical CNS aut...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450115666141029234644

    authors: Bonnan M,Ferrari S,Bertandeau E,Demasles S,Krim E,Miquel M,Barroso B

    更新日期:2014-01-01 00:00:00

  • Identifying and attaining LDL-C goals: mission accomplished? Next target: new therapeutic options to raise HDL-C levels.

    abstract::Currently, low density lipoprotein cholesterol (LDL-C) levels are the main, if not the only, lipid target in the effort to reduce cardiovascular disease (CVD) morbidity and mortality. Several primary and secondary CVD prevention trials with statins shaped current guidelines and provided detailed targets across a range...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945007780058933

    authors: Athyros VG,Mikhailidis DP,Kakafika AI,Karagiannis A,Hatzitolios A,Tziomalos K,Ganotakis ES,Liberopoulos EN,Elisaf M

    更新日期:2007-03-01 00:00:00

  • Cell death targeting therapies in B lymphoid malignancies.

    abstract::Programmed cell death, commonly associated with the term apoptosis, is an integrated intracellular program that plays a critical role in lymphoid tissue homeostasis. Alterations in this highly regulated process is a common feature of most lymphoid malignancies, thus facilitating tumor escape from traditional chemother...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945010791320863

    authors: Saborit-Villarroya I,Roué G,López-Guerra M,Alonso R,Xargay-Torrent S,Rosich L,Colomer D

    更新日期:2010-07-01 00:00:00

  • Advancement of Mechanisms of Coxsackie Virus B3-Induced Myocarditis Pathogenesis and the Potential Therapeutic Targets.

    abstract::Viral myocarditis is a cardiac disease caused by Group B Coxsackie virus of Enterovirus genus in the Picorna viridae family. It causes heart failure in children, young and adults. Ten Percent (10%) of acute heart failure and 12% of sudden deaths in young and adults who are less than 40 years is due to this viral myoca...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450120666190618124722

    authors: Daba TM,Zhao Y,Pan Z

    更新日期:2019-01-01 00:00:00

  • Adoptive Immunotherapy For Leukemia With Ex vivo Expanded T Cells.

    abstract::The development of novel T cell therapies to target leukemia has facilitated the translation of this approach for hematologic malignancies. Different methods of manufacturing leukemia-specific T cells have evolved, along with additional measures to increase the safety of this therapy. This is an overview of expanded T...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160209143529

    authors: Cruz CR,Bollard CM

    更新日期:2017-01-01 00:00:00

  • Raloxifene.

    abstract::Efforts to interfere with the initiation and promotion of breast and other cancers by endocrine manipulation are not new. It is of obvious benefit to cancer patients to administer substances that combine minimal general toxicity with maximal oestrogen inhibition. Raloxifene is a relatively recent addition to a group o...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450013348263

    authors: Kellen JA

    更新日期:2001-12-01 00:00:00

  • TGF-betal/Smad signaling in prostate cancer.

    abstract::Adenocarcinoma of the prostate is the most common type of cancer, excluding skin cancer, and the second leading cause of cancer death in adult men in the United States. The lifetime risk for developing symptomatic prostate cancer is one in five for an American man. A pivotal step in carcinogenesis is a shift in the ba...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450033491118

    authors: Bello-DeOcampo D,Tindall DJ

    更新日期:2003-04-01 00:00:00

  • Protein Arginine Deiminases and Associated Citrullination: Physiological Functions and Diseases Associated with Dysregulation.

    abstract::Human proteins are subjected to more than 200 known post-translational modifications (PTMs) (e.g., phosphorylation, glycosylation, ubiquitination, S-nitrosylation, methylation, Nacetylation, and citrullination) and these PTMs can alter protein structure and function with consequent effects on the multitude of pathways...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450116666150202160954

    authors: Witalison EE,Thompson PR,Hofseth LJ

    更新日期:2015-01-01 00:00:00

  • Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer.

    abstract::Resveratrol (3,4',5 tri-hydroxystilbene) is a phytoalexin produced in hudge amount in grapevine skin in response to infection by Bothrytis cinerea. This production of resveratrol blocks the proliferation of the pathogen, thereby acting as a natural antibiotic. Numerous studies have reported interesting properties of t...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006776359331

    authors: Delmas D,Lançon A,Colin D,Jannin B,Latruffe N

    更新日期:2006-04-01 00:00:00

  • Pharmacogenomics in the Americas: the impact of genetic admixture.

    abstract::In this review we focus on the impact of genetic admixture on pharmacogenomics in the American continent, where five centuries of intermarriage between Amerindians, European and Africans, resulted in the extensive population heterogeneity observed nowadays. We compare two alternative views of human genomic variation, ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945006779025392

    authors: Suarez-Kurtz G,Pena SD

    更新日期:2006-12-01 00:00:00

  • Alternatives to conventional vaccines--mediators of innate immunity.

    abstract::Vaccines have been described as "weapons of mass protection". The eradication of many diseases is testament to their utility and effectiveness. Nevertheless, many vaccine preventable diseases remain prevalent because of political and economic barriers. Additionally, the effects of immaturity and old age, therapies tha...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450043490703

    authors: Eisen DP,Liley HG,Minchinton RM

    更新日期:2004-01-01 00:00:00

  • The Role of the Oxysterol/EBI2 Pathway in the Immune and Central Nervous Systems.

    abstract::Oxysterols are pleiotropic messengers interacting with multiple receptor systems. One of the cognate receptors for oxysterols is EBI2, a G protein-coupled receptor highly expressed in the cells of the immune system. Here we discuss the receptor's role in the adapted immunity and inflammation as well as the receptor's ...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/1389450117666160217123042

    authors: Rutkowska A,Dev KK,Sailer AW

    更新日期:2016-01-01 00:00:00

  • Mucosal healing in ulcerative colitis: where do we stand?

    abstract::Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathol...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945011796818216

    authors: Fiorino G,Cesarini M,Indriolo A,Malesci A

    更新日期:2011-09-01 00:00:00

  • Patient-controlled analgesia.

    abstract::Using a portable infusion pump, intravenous opioid patient-controlled analgesia (PCA) permits a patient to self-deliver a small bolus of opioid to achieve prompt relief without over sedation. Use of PCA for pain management is increasing in hospitals, largely because it can provide equivalent or better analgesia than c...

    journal_title:Current drug targets

    pub_type: 杂志文章,评审

    doi:10.2174/138945005774574524

    authors: Mann C,Ouro-Bang'na F,Eledjam JJ

    更新日期:2005-11-01 00:00:00