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Health Technology Assessment... Jan 2007A systematic review was undertaken and an economic model constructed to evaluate the clinical effectiveness and cost-effectiveness of docetaxel (Taxotere,... (Review)
Review
A systematic review and economic model of the clinical effectiveness and cost-effectiveness of docetaxel in combination with prednisone or prednisolone for the treatment of hormone-refractory metastatic prostate cancer.
OBJECTIVES
A systematic review was undertaken and an economic model constructed to evaluate the clinical effectiveness and cost-effectiveness of docetaxel (Taxotere, Sanofi-Aventis) in combination with prednisone/prednisolone for the treatment of metastatic hormone-refractory prostate cancer (mHRPC). The main comparators considered were other established chemotherapy regimens and best supportive care.
DATA SOURCES
Twenty-one resources (including MEDLINE, EMBASE and the Cochrane Library) were searched to April 2005.
REVIEW METHODS
Two reviewers independently assessed studies for inclusion. Data from included studies were extracted and quality assessed. Where appropriate, outcomes were synthesised using formal analytic approaches. A new economic model was developed in order to establish the cost-effectiveness of docetaxel compared with a range of potential comparators. A separate review was undertaken to identify sources of utility data required to estimate quality-adjusted life-years (QALYs). Sensitivity analyses were also undertaken to explore the robustness of the main analysis to alternative assumptions related to quality of life. Monte Carlo simulation was used to propagate uncertainty in input parameters through the model in such a way that the results of the analysis could be presented with their uncertainty. The impact of uncertainty surrounding the decision was established using value of information and implementation approaches.
RESULTS
Seven randomised controlled trials were identified that met the inclusion criteria. A direct comparison of docetaxel plus prednisone versus mitoxantrone plus prednisone in an open-label randomised trial showed improved outcomes for docetaxel plus prednisone in terms of overall survival, quality of life, pain and prostate-specific antigen decline. Two other chemotherapy regimens that included docetaxel: docetaxel plus estramustine and docetaxel plus prednisone plus estramustine, also showed improved outcomes in comparison with mitoxantrone plus prednisone. Indirect comparison suggested that docetaxel plus prednisone seems to be superior to corticosteroids alone in terms of overall survival. Conclusions on cost-effectiveness were primarily informed by the results of the in-house model. This indicated that mitoxantrone plus a corticosteroid is probably cheaper and more effective than corticosteroid alone. Compared with mitoxantrone plus prednisone/prednisolone, the use of docetaxel plus prednisone/prednisolone (3-weekly) appears cost-effective only if the NHS is prepared to pay 33,000 pounds per QALY. The incremental cost-effectiveness ratio associated with docetaxel plus prednisone (3-weekly) remained fairly robust to these variations with estimates ranging from 28,000 pounds to 33,000 pounds per QALY. Value of information analysis revealed that further research is potentially valuable. Given a maximum acceptable ratio of 30,000 pounds per QALY, the expected value of information was estimated to be approximately 13 million pounds.
CONCLUSIONS
This systematic review of the research suggests that docetaxel plus prednisone seems to be the most effective treatment for men with mHRPC. The economic model suggests that treatment with docetaxel plus prednisone/prednisolone is cost-effective in patients with mHRPC provided the NHS is prepared to pay 33,000 pounds per additional QALY. Future research should include the direct assessment of quality of life and utility gain associated with different treatments, including the effect of adverse events of treatment, using generic instruments, which are suitable for the purposes of cost-effectiveness analyses.
Topics: Antineoplastic Agents; Docetaxel; Drug Therapy, Combination; Glucocorticoids; Humans; Male; Models, Economic; Neoplasm Metastasis; Prednisone; Prostatic Neoplasms; Quality-Adjusted Life Years; Taxoids; Treatment Outcome; United Kingdom
PubMed: 17181985
DOI: 10.3310/hta11020 -
Acta Myologica : Myopathies and... May 2012Steroids have been used since two decades and several trials were conducted to establish their efficacy in DMD patients with various regimens. The clinical outcomes... (Review)
Review
Steroids have been used since two decades and several trials were conducted to establish their efficacy in DMD patients with various regimens. The clinical outcomes showed increased function in the treated boys, and in a single trial with deflazacort, prolongation of ambulation but with different side effects. Steroids clinical efficacy is now established. The main concern is to increase steroid efficacy and decrease side effect and toxicity. A trial comparing daily prednisone, deflazacort and intermittent glucocorticoids (prednisone 10 days on/10 days off) (FOR-DMD) is starting under NIH grant. The primary outcomes will be muscle strength, forced vital capacity and patient/parents satisfaction.
Topics: Exercise Test; Glucocorticoids; Humans; Immunosuppressive Agents; Muscle Strength; Muscular Dystrophy, Duchenne; Prednisone; Pregnenediones
PubMed: 22655511
DOI: No ID Found -
The British Journal of Ophthalmology Dec 2002
Topics: Administration, Oral; Anti-Inflammatory Agents; Colchicine; Drug Therapy, Combination; Fibrosis; Humans; Postoperative Complications; Prednisone; Trabeculectomy
PubMed: 12446354
DOI: 10.1136/bjo.86.12.1323 -
Cell Communication and Signaling : CCS Jun 2022Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the...
BACKGROUND
Autoimmune hepatitis (AIH) is a chronic, immune-mediated liver dysfunction. The gut microbiota and T follicular helper (Tfh) cells play critical roles in the immunopathogenesis and progression of AIH. We aimed to investigate the effect of gut microbiota combined with prednisone therapy on Tfh cell response in AIH.
METHODS
Samples from AIH patients and mouse model of experimental autoimmune hepatitis (EAH) were analyzed using real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, flow cytometry, and hematoxylin-eosin staining to determine the role of gut microbiota on AIH.
RESULTS
Lactobacillus significantly increased the levels of Bacteroides fragilis, Clostridium, Clostridium leptum, Bifidobacterium, and Lactobacillus and significantly enhanced the suppressive effects of prednisone on the levels of AIH clinical indexes in AIH patients. Lactobacillus exerts the same prptective effects as prednisone in EAH mice and enhanced the effects of prednisone. Lactobacillus also reinforced the inhibitory effects of prednisone on the levels of serum IL-21 and the proportions of Tfh cells in peripheral blood mononuclear cells. Mechanistically, prednisone and Lactobacillus regulated Tfh cell response in EAH mice in an MyD88/NF-κB pathway-dependent manner.
CONCLUSION
Our results suggested a therapeutic potential of Lactobacillus in the prednisone-combined treatment of AIH. Video Abstract.
Topics: Animals; Gastrointestinal Microbiome; Hepatitis, Autoimmune; Humans; Lactobacillus; Leukocytes, Mononuclear; Mice; Prednisone; T Follicular Helper Cells
PubMed: 35658901
DOI: 10.1186/s12964-021-00819-7 -
Medicine Jun 2020The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is... (Comparative Study)
Comparative Study
Effectiveness and safety of thymectomy plus prednisone compares with prednisone monotherapy for the treatment of non-thymomatous Myasthenia Gravis: Protocol for a systematic review.
BACKGROUND
The pathogenesis of myasthenia gravis (MG) has strong connection with thymic abnormalities. Thymic hyperplasia or thymoma can be found with most patients. Thymectomy is currently one of the regular treatment in clinic, which is, however, still controversial for non-thymomatous MG. This research will assess the effectiveness and safety of thymectomy plus prednisone compared to prednisone monotherapy for the treatment of non-thymomatous MG systematically.
METHODS
According to eligibility and ineligibility criteria, 8 databases, including PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan-fang Database, Chinese Biomedical Literature Database (CBM), China Science and Technology Journal Database (CSTJ), will be searched to gather the up-to-standard articles from September 2000 to September 2025. Inclusion criteria are as follows: randomized controlled trials of thymectomy plus prednisone for the treatment of non-thymomatous MG. The quantitative myasthenia gravis score (QMG) and the dose of prednisone required will be accepted as the main outcomes. Data synthesis, subgroup analysis, sensitivity analysis, and meta-regression analysis will be conducted using RevMan 5.3 software. We will use Egger or Begg test to evaluate symmetry on a funnel plot which is made to assess reporting bias, and use trial sequential analysis (TSA) to exclude the probability of false positives.
RESULTS
This systematic review will measure the QMG and the dose of prednisone required, the myasthenia gravis activities of daily living scale scores (MG-ADL), treatment-associated complications, incidence of myasthenic crisis and other aspects to comprehensively assess the clinical benefits of thymectomy plus prednisone for MG patients without thymoma.
CONCLUSION
The conclusion of this study will achieve convincing evidence to evaluate the effectiveness and safety of thymectomy plus prednisone for the treatment of non-thymomatous MG.
PROSPERO REGISTRATION NUMBER
CRD 42020167735.
Topics: Anti-Inflammatory Agents; Combined Modality Therapy; Humans; Myasthenia Gravis; Prednisone; Thymectomy; Treatment Outcome
PubMed: 32569233
DOI: 10.1097/MD.0000000000020832 -
Journal of Neuromuscular Diseases 2023Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited.
BACKGROUND
Evidence on the long-term efficacy of steroids in Duchenne muscular dystrophy (DMD) after loss of ambulation is limited.
OBJECTIVE
Characterize and compare disease progression by steroid treatment (prednisone, deflazacort, or no steroids) among non-ambulatory boys with DMD.
METHODS
Disease progression was measured by functional status (Performance of Upper Limb Module for DMD 1.2 [PUL] and Egen Klassifikation Scale Version 2 [EK] scale) and by cardiac and pulmonary function (left ventricular ejection fraction [LVEF], forced vital capacity [FVC] % -predicted, cough peak flow [CPF]). Longitudinal changes in outcomes, progression to key disease milestones, and dosing and body composition metrics were analyzed descriptively and in multivariate models.
RESULTS
This longitudinal cohort study included 86 non-ambulatory patients with DMD (mean age 13.4 years; n = 40 [deflazacort], n = 29 [prednisone], n = 17 [no steroids]). Deflazacort use resulted in slower average declines in FVC % -predicted vs. no steroids (+3.73 percentage points/year, p < 0.05). Both steroids were associated with significantly slower average declines in LVEF, improvement in CPF, and slower declines in total PUL score and EK total score vs. no steroids; deflazacort was associated with slower declines in total PUL score vs. prednisone (all p < 0.05). Both steroids also preserved functional abilities considered especially important to quality of life, including the abilities to perform hand-to-mouth function and to turn in bed at night unaided (all p < 0.05 vs. no steroids).
CONCLUSIONS
Steroid use after loss of ambulation in DMD was associated with delayed progression of important pulmonary, cardiac, and upper extremity functional deficits, suggesting some benefits of deflazacort over prednisone.
Topics: Male; Humans; Adolescent; Prednisone; Stroke Volume; Longitudinal Studies; Quality of Life; Ventricular Function, Left; Muscular Dystrophy, Duchenne; Disease Progression
PubMed: 36565131
DOI: 10.3233/JND-221575 -
Molecular Metabolism Aug 2022Mitochondrial capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian...
OBJECTIVE
Mitochondrial capacity is critical to adapt the high energy demand of the heart to circadian oscillations and diseased states. Glucocorticoids regulate the circadian cycle of energy metabolism, but little is known about how circadian timing of exogenous glucocorticoid dosing directly regulates heart metabolism through cardiomyocyte-autonomous mechanisms. While chronic once-daily intake of glucocorticoids promotes metabolic stress and heart failure, we recently discovered that intermittent once-weekly dosing of exogenous glucocorticoids promoted muscle metabolism in normal and obese skeletal muscle. However, the effects of glucocorticoid intermittence on heart metabolism and heart failure remain unknown. Here we investigated the extent to which circadian time of dosing regulates the effects of the glucocorticoid prednisone in heart metabolism and function in conditions of single pulse or chronic intermittent dosing.
METHODS AND RESULTS
In WT mice, we found that prednisone improved cardiac content of NAD and ATP with light-phase dosing (ZT0), while the effects were blocked by dark-phase dosing (ZT12). The drug effects on mitochondrial function were cardiomyocyte-autonomous, as shown by inducible cardiomyocyte-restricted glucocorticoid receptor (GR) ablation, and depended on an intact cardiomyocyte clock, as shown by inducible cardiomyocyte-restricted ablation of Brain and Muscle ARNT-like 1 (BMAL1). Conjugating time-of-dosing with chronic intermittence, we found that once-weekly prednisone improved metabolism and function in heart after myocardial injury dependent on circadian time of intake, i.e. with light-phase but not dark-phase dosing.
CONCLUSIONS
Our study identifies cardiac-autonomous mechanisms through which circadian-specific intermittent dosing reconverts glucocorticoid drugs to metabolic boosters for the heart.
Topics: Animals; Circadian Clocks; Glucocorticoids; Heart Failure; Mice; Myocytes, Cardiac; Prednisone
PubMed: 35717025
DOI: 10.1016/j.molmet.2022.101528 -
The Journal of Pharmacology and... Nov 2020The pharmacokinetics (PK) of prednisolone (PNL) exhibit nonlinearity related to plasma protein binding, tissue binding, metabolic interconversion with prednisone (PN),...
The pharmacokinetics (PK) of prednisolone (PNL) exhibit nonlinearity related to plasma protein binding, tissue binding, metabolic interconversion with prednisone (PN), and renal elimination. Blood and 11 tissues were collected from male Wistar rats after steady-state (SS) infusion and after subcutaneous boluses of 50 mg/kg of PNL. Concentrations of PNL and PN were measured by liquid chromatography-tandem mass spectrometry. Plasma and tissue profiles were described using a complex physiologically based pharmacokinetics (PBPK) model. Concentrations of PN and PNL were in rapid equilibrium in plasma and tissues. The tissue partition coefficients ( ) of PNL calculated from most subcutaneously dosed tissue and plasma areas were similar to SS infusion and in silico values. The blood-to-plasma ratio of PNL was 0.71 with similar red blood cell and unbound-plasma concentrations. Plasma protein binding (60%-90%) was related to corticosteroid-binding globulin (CBG) saturation. Tissue distribution was nonlinear. The equilibrium dissociation constant ( ) of PNL shared by all tissues was 3.01 ng/ml, with the highest binding in muscle, followed by liver, heart, intestine, and bone and the lowest binding in skin, spleen, fat, kidney, lung, and brain. Fat and bone distribution assumed access only to interstitial space. Brain PNL concentrations ( = 0.05) were low owing to presumed P-glycoprotein-mediated efflux. Clearances of CBG-free PNL were 1789 from liver and 191.2 ml/h from kidney. The PN/PNL ratio was nonlinear for plasma, spleen, heart, intestine, bone, fat, and linear for the remaining tissues. Our PBPK model with multiple complexities well described the PK profiles of PNL and PN in blood, plasma, and diverse tissues. SIGNIFICANCE STATEMENT: Because steroids, such as prednisolone and prednisone, have similar and complex pharmacokinetics properties in various species, receptors in most tissues, and multiple therapeutic and adverse actions, this physiologically based pharmacokinetics (PBPK) model may provide greater insights into the pharmacodynamic complexities of corticosteroids. The complex properties of these compounds require innovative PBPK modeling approaches that may be instructive for other therapeutic agents.
Topics: Animals; Male; Models, Biological; Nonlinear Dynamics; Prednisolone; Prednisone; Rats; Rats, Wistar; Tissue Distribution
PubMed: 32883831
DOI: 10.1124/jpet.120.000191 -
Canadian Medical Association Journal Aug 1955
Topics: Humans; Prednisone; Steroids
PubMed: 13240588
DOI: No ID Found -
Microbiology Spectrum Dec 2021Prednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of...
Prednisone (PRED) is a synthetic glucocorticoid (GC) widely used in immune-mediated diseases for its immunosuppressive and anti-inflammatory properties. The effects of GC are achieved by genomic and nongenomic mechanisms. However, the nongenomic effects are largely unknown. Thus, we aimed to investigate how long-term prednisone therapy changes the composition of the gut microbiota and fecal metabolites in rats. Male Sprague-Dawley rats were randomly assigned to a control (CON) group and a PRED group, which received prednisone treatment daily for 6 weeks by gavage. The V3 to V4 regions of bacterial 16S rRNA genes were amplified and sequenced after the total bacterial DNA was extracted from fecal samples. The alpha and beta diversities were calculated. The compositional alteration of the gut microbiota at different taxonomic levels was analyzed using the Metastats method. Meanwhile, the fecal metabolites were quantitated in an ultra-performance liquid chromatography system. Similar microbial richness and diversity between the CON and PRED groups were indicated by the alpha diversity results. The gut microbial communities differed significantly between two groups. The relative abundances of the genera , , and XIVb decreased, whereas that of increased significantly in rats after the 6-week prednisone treatment. In total, 11 downregulated and 10 upregulated fecal metabolites were identified. Differential fecal metabolites were enriched in the pathways, including phenylalanine metabolism, butanoate metabolism, and propanoate metabolism. The lowered production of short-chain fatty acids was associated with the decreased relative abundance of the genera and and increased abundance of the genus . The composition of the gut microbiota and fecal metabolites was changed after long-term prednisone treatment. This may help us to understand the pharmacology of prednisone. Prednisone is widely used in chronic glomerular diseases, immunological disorders, and rheumatic diseases for its anti-inflammatory and immunosuppressive properties. It is a synthetic glucocorticoid (GC) that shows therapeutic effects after conversion to prednisolone by the liver. Prolonged GC therapy causes anti-inflammatory effects; it also results in a variety of adverse events, including obesity, hypertension, psychiatric symptoms, and dyslipidemia. The therapeutic effects and adverse events of GCs may be associated with changes in the gut microbiota, as the host might be affected by the metabolites generated by the altered gut microbes. Thus, we investigated how long-term prednisone therapy changed the composition of the gut microbiota and fecal metabolites in rats. This study may shed new light on the pharmacology of prednisone.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; DNA, Bacterial; Feces; Gastrointestinal Microbiome; Male; Prednisone; RNA, Ribosomal, 16S; Rats; Rats, Sprague-Dawley
PubMed: 34756061
DOI: 10.1128/Spectrum.00650-21