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Orphanet Journal of Rare Diseases Sep 2023Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any...
Mepolizumab at the dose of 300 mg/4 weeks has been recently approved as an add-on therapy for patients with uncontrolled hypereosinophilic syndrome (HES) without any identifiable non-hematologic secondary cause. According to the available real-life evidence mepolizumab 300 mg and 100 mg, licensed for severe eosinophilic asthma, are comparable in terms of drug efficacy. However, the clinical rationale for selecting one dose or the other has not been explored. We investigated the efficacy and safety of mepolizumab 100 mg in idiopathic HES (I-HES) patients as a steroid sparing strategy for disease remission maintenance by assessing clinical conditions, blood eosinophil count (BEC) and adverse events at baseline and at 3-6-12 months follow-up. Overall, 11 patients were enrolled (females 4-36%) with a median age of 62 years (IQR 55.0-72.0). At 3-month visit both prednisone daily dose and BEC significantly decreased from baseline, whilst a substantial improvement of Brief fatigue inventory score (BFI) was not recorded before the 6 months assessment. More than 70% of patients completely stopped prednisone at 12-months follow-up, without any flare in terms of BEC and BFI. No adverse event was registered. Although larger studies are needed, our report firstly describes that in a well-defined population, diagnosed with I-HES and in disease remission, low dose mepolizumab is a safe and effective steroid-sparing option for remission maintenance. It suggests that a personalized treatment dose might be explored according to the disease classification and activity at the time of biologic treatment start.
Topics: Female; Humans; Middle Aged; Aged; Prednisone; Precision Medicine; Hypereosinophilic Syndrome
PubMed: 37752586
DOI: 10.1186/s13023-023-02918-9 -
AAPS PharmSciTech Sep 2013The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet...
The purpose of this study is to enhance the dissolution rate of prednisone by co-grinding with Neusilin to form a complex that can be incorporated into a mini-tablet formulation for pediatrics. Prednisone-Neusilin complex was co-grinded at various ratios (1:1, 1:3, 1:5, and 1:7). The physicochemical properties of the complex were characterized by various analytical techniques including: differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), scanning electron microscope (SEM), particle size, surface area, solubility, and dissolution rate. The co-grinded prednisone-Neusilin complex (1:7) was blended with other excipients and was formulated into a 2-mm diameter mini-tablet. The mini-tablets were further evaluated for thickness, weight, content uniformity, and dissolution rate. To improve taste masking and stability, mini-tablets were coated by dip coating with Eudragit® EPO solution. DSC and XRPD results showed that prednisone was transformed from crystalline state into amorphous state after co-grinding with Neusilin. Particle size, surface area, and SEM results confirmed that prednisone was adsorbed to Neusilin's surface. Co-grinded prednisone-Neusilin complex (1:7) had a solubility of 0.24 mg/mL and 90% dissolved within 20 min as compared to crystalline prednisone which had a solubility of 0.117 mg/mL and 30% dissolved within 20 min. The mini-tablets containing co-grinded prednisone-Neusilin complex (1:7) exhibited acceptable physicochemical and mechanical properties including dissolution rate enhancement. These mini-tablets were successfully dip coated in Eudragit® EPO solution to mask the taste of the drug during swallowing. This work illustrates the potential use of co-grinded prednisone-Neusilin to enhance solubility and dissolution rate as well as incorporation into a mini-tablet formulation for pediatric use.
Topics: Aluminum Compounds; Calorimetry, Differential Scanning; Child; Humans; Magnesium Compounds; Microscopy, Electron, Scanning; Pediatrics; Powder Diffraction; Prednisone; Silicates; Solubility; Tablets
PubMed: 23761262
DOI: 10.1208/s12249-013-9981-x -
Antimicrobial Agents and Chemotherapy Sep 2013Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed... (Clinical Trial)
Clinical Trial
Prednisone, a corticosteroid frequently used to treat common AIDS-related illnesses and comorbidities, has been shown to induce drug metabolism. This study was performed to determine whether prednisone coadministration affected the pharmacokinetics of dolutegravir (DTG). In this open-label, repeat-dose study, 12 healthy subjects were administered DTG at 50 mg daily alone for 5 days and then with concomitant prednisone for 10 days (prednisone at 60 mg daily for 5 days, followed by a 5-day taper). Serial blood sampling and safety assessments were performed during the trial. Pharmacokinetic parameters were determined using noncompartmental methods and geometric least-square mean ratios, and 90% confidence intervals were generated. Coadministration of DTG and 5-day high-dose prednisone with a 5-day taper had a modest effect on DTG exposure. The area under the DTG plasma concentration-time curve, maximum observed DTG concentration, and 24-hour postdose DTG concentration were increased by 11%, 6%, and 17%, respectively, on day 10 of the combination. Similar results were observed after 5 days of DTG and prednisone. Dolutegravir and prednisone coadministration was well tolerated. The changes in plasma exposures of DTG in healthy individuals as a result of prednisone dosing were not clinically significant. No dose adjustment is required for DTG coadministered with prednisone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01425099.).
Topics: Adolescent; Adult; Aged; Area Under Curve; Drug Administration Schedule; Drug Interactions; Female; HIV Integrase Inhibitors; Healthy Volunteers; Heterocyclic Compounds, 3-Ring; Humans; Male; Middle Aged; Oxazines; Piperazines; Prednisone; Pyridones
PubMed: 23817375
DOI: 10.1128/AAC.00728-13 -
Pharmacoepidemiology and Drug Safety Apr 2018To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose,...
PURPOSE
To characterize prednisone use in pregnant women with rheumatoid arthritis using individual-level heat-maps and clustering individual trajectories of prednisone dose, and to evaluate the association between prednisone dose trajectory groups and gestational length.
METHODS
This study included pregnant women with rheumatoid arthritis who enrolled in the MotherToBaby Autoimmune Diseases in Pregnancy Study (2003-2014) before gestational week 20 and reported prednisone use without another oral glucocorticoid during pregnancy (n = 254). Information on medication use and pregnancy outcomes was collected by telephone interview plus by medical record review. Prednisone daily dose and cumulative dose were plotted by gestational day using a heat map for each individual. K-means clustering was used to cluster individual trajectories of prednisone dose into groups. The associations between trajectory group and demographics, disease severity measured by the Health Assessment Questionnaire at enrollment, and gestational length were evaluated.
RESULTS
Women used prednisone 3 to 292 days during pregnancy, with daily doses ranging from <1 to 60 mg. Total cumulative dose ranged from 8 to 6225 mg. Disease severity, non-biologic disease modifying anti-rheumatic drug use, and gestational length varied significantly by trajectory group. After adjusting for disease severity, non-biologic disease modifying anti-rheumatic drug use, and other covariates, the highest vs lowest daily dose trajectory group was associated with reduced gestational age at delivery (β: -2.3 weeks (95%: -3.4, -1.3)), as was the highest vs lowest cumulative dose trajectory group (β: -2.6 weeks (95%: -3.6, -1.5)).
CONCLUSIONS
In pregnant women with rheumatoid arthritis, patterns of higher prednisone dose were associated with shorter gestational length compared with lower dose.
Topics: Administration, Oral; Adult; Arthritis, Rheumatoid; Dose-Response Relationship, Drug; Female; Gestational Age; Glucocorticoids; Humans; Prednisone; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Prospective Studies; Severity of Illness Index
PubMed: 29488292
DOI: 10.1002/pds.4410 -
Journal of Ocular Pharmacology and... 2019To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and...
To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels. Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at selected times. Prednisone and prednisolone were quantified in tears by liquid chromatography-mass spectrometry. Lacrimal prednisone and prednisolone concentrations ranged from 2 to 523 ng/mL and 5 to 191 ng/mL, respectively. Drug concentrations were overall greater in dogs receiving higher doses of prednisone, but were not correlated with tear flow rate. Eyes with conjunctivitis often had larger amounts of prednisone and prednisolone in tear fluid compared to control eyes (up to +64%), but differences were not statistically significant. Significantly greater, but clinically insignificant, levels of prednisolone were found in eyes with severe versus mild conjunctivitis for oral prednisone doses ≥1.0 mg/kg. Disruption of the blood-tear barrier with conjunctivitis did not significantly affect drug levels in tears. Based on drug PK in tears, oral prednisone is likely safe for the management of reflex uveitis and ocular surface diseases. However, further prospective trials using systemic corticotherapy in diseased animals are warranted to confirm findings from this preclinical study.
Topics: Administration, Oral; Animals; Chromatography, Liquid; Conjunctivitis; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Female; Glucocorticoids; Mass Spectrometry; Prednisolone; Prednisone; Tears
PubMed: 31070497
DOI: 10.1089/jop.2019.0020 -
JAMA Network Open Mar 2024The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The association between the use of bone-modifying agents (BMAs) and the outcomes among patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with abiraterone acetate plus prednisone (AAP) remains unclear.
OBJECTIVE
To investigate the association between BMA use and the outcomes of patients with mCSPC receiving AAP.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, a post hoc analysis of individual participant data from the LATITUDE trial was performed. The LATITUDE trial, a phase 3 randomized clinical trial, aimed to assess the efficacy of AAP and androgen deprivation therapy (ADT) vs dual-placebo and ADT in patients with high-risk mCSPC (data cutoff, August 15, 2018). Eligible patients had newly diagnosed prostate cancer with metastases and at least 2 of 3 high-risk factors (Gleason score ≥8, presence of ≥3 lesions on bone scan, or presence of measurable visceral metastasis). The trial was conducted at 235 sites in 34 countries. Data for the present study were evaluated from July 18 to September 23, 2023.
EXPOSURES
Use of BMAs was defined as the administration of bisphosphonates and denosumab within 90 days before and after randomization.
MAIN OUTCOMES AND MEASURES
The primary outcomes were time to skeletal-related events (SREs) and overall survival (OS). An SRE was defined as a clinical or pathological fracture, spinal cord compression, palliative radiation to bone, or surgery involving bone. Differences in these outcomes were examined using the restricted mean survival time from inverse probability of treatment weighting-adjusted Kaplan-Meier curves, estimated until the last event was observed (longest time observed, 63.9 months). Treatment × covariate interactions were analyzed using weighted Cox proportional hazards regression models for the total cohort.
RESULTS
In the total cohort of 1199 patients (956 [79.7%] younger than 75 years), 597 (49.8%) received AAP and ADT, including 474 (79.4%) younger than 75 years and 384 (64.3%) with more than 10 bone metastases (AAP cohort); 602 (50.2%) were treated with dual placebo and ADT, including 482 (80.1%) younger than 75 years and 377 (62.6%) with more than 10 bone metastases (ADT cohort). In the AAP cohort, 132 patients (22.1%) received BMAs, while in the ADT cohort, 131 (21.8%) did. Zoledronic acid was the most frequently administered BMA in both the AAP (93 [70.5%]) and the ADT (88 [67.2%]) cohorts. During the median follow-up of 51.8 (IQR, 47.2-57.0) months in the AAP cohort, BMA use was associated with a longer time to SRE (difference, 7.8 [95% CI, 4.2-11.3] months) but not with OS (difference, 1.6 [95% CI, -2.5 to 5.8] months). In the ADT cohort, BMA use was associated with both time to SRE (difference, 9.3 [95% CI, 5.2-13.3] months) and OS (difference, 5.5 [95% CI, 3.2-9.8] months). No evidence was found that the outcomes of BMA varied by AAP or ADT (hazard ratio for time to SRE, 0.99 [95% CI, 0.48-2.08]; P = .99 for interaction; hazard ratio for OS, 1.31 [95% CI, 0.88-1.96]; P = .18 for interaction).
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that use of BMAs was associated with a longer time to SRE in patients with high-risk mCSPC treated with ADT, with or without AAP, suggesting that BMA use might provide benefits to this population.
Topics: Male; Humans; Abiraterone Acetate; Prostatic Neoplasms; Androgen Antagonists; Cohort Studies; Prednisone; Castration
PubMed: 38488793
DOI: 10.1001/jamanetworkopen.2024.2467 -
Endokrynologia Polska 2023The study aimed to explore the efficacy and safety of low-dose (LD) and regular-dose (RD) prednisone (PDN) for the treatment of subacute thyroiditis (SAT). (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
The study aimed to explore the efficacy and safety of low-dose (LD) and regular-dose (RD) prednisone (PDN) for the treatment of subacute thyroiditis (SAT).
MATERIAL AND METHODS
Patients were randomly allocated using the block randomization method to the 2 groups. The primary outcome was the time required for PDN treatment. Secondary outcomes included percentages of relapse, mean score for the Morisky Medication Adherence Scale-8© (MMAS-8), time required for symptoms to resolve, cumulative PDN dose (mg), and mean erythrocyte sedimentation rate (ESR) at 2 weeks and at baseline.
RESULTS
The study cohort included 77 patients, randomized 74 participants, and 68 completed the study. There was no significant difference in the treatment duration between the LD and RD groups (55.31 ± 14.05 vs. 61.25 ± 19.95 days, p = 0.053). The mean difference in the time required for PDN treatment between the LD and RD groups was -1.86 [95% confidence interval (CI) = -10.64 to 6.92] days, which was within the non-inferiority margin of 7 days. There was a significant difference in the mean score for MMAS-8 between the LD and RD groups (5.84 ± 0.88 vs. 5.33 ± 1.12, p = 0.031). Also, there was a significant difference in the cumulative PDN dose between the LD and RD groups (504.22 ± 236.86 vs. 1002.28 ± 309.86, p = 0.046). The ESR at 2 weeks was statistically significant compared to baseline values in both groups, with pre-treatment and post-treatment ESRs of 49.91 ± 24.95 and 17.91 ± 12.60/mm/h, (p < 0.0001) in the LD group and 65.08 ± 21.77 and 17.23 ± 13.61/mm/h (p < 0.0001) in the RD group.
CONCLUSION
Low-dose PDN therapy may be sufficient to achieve complete recovery and better outcomes for SAT. This study is registered with the Chinese Clinical Trial Registry (02/10/2021 ChiCTR2100051762).
Topics: Humans; Prednisone; Thyroiditis, Subacute; Prospective Studies; Treatment Outcome; Neoplasm Recurrence, Local
PubMed: 37155300
DOI: 10.5603/EP.a2023.0023 -
Kidney International. Supplement Jun 1999The condition known as IgA nephropathy was first identified when Berger observed mesangial staining for IgA in healthy patients with isolated hematuria. These patients... (Review)
Review
The condition known as IgA nephropathy was first identified when Berger observed mesangial staining for IgA in healthy patients with isolated hematuria. These patients often presented with recurrent synpharyngitic hematuria or less frequently with asymptomatic microscopic hematuria and proteinuria. Although initially considered benign, we now recognize it as a common cause of end-stage renal failure. The overall prognosis may be better than suggested in the literature, as patients with mild asymptomatic hematuria are often not biopsied and, therefore, frequently are not included in published articles. We reviewed prospective and retrospective adult studies published after 1976 and analyzed them to produce evidence-based recommendations. Patients with proteinuria over 3 g/day, mild glomerular changes only, and preserved renal function (creatinine clearance over 70 ml/min) should be treated with prednisone. Steroids reduce proteinuria (grade B recommendation) and stabilize kidney function (grade C). The combination of cyclophosphamide, dipyridamole and warfarin should not be used (grade A), nor should cyclosporine A (grade B). In patients with progressive disease (creatinine clearance of less than 70 ml/min), fish oil should be given (grade B). A tonsillectomy could reduce proteinuria and hematuria in those patients with recurrent tonsillitis (grade D). Those with hypertension should be treated promptly with an angiotensin-converting enzyme inhibitor (grade B).
Topics: Adult; Anti-Inflammatory Agents; Evidence-Based Medicine; Glomerulonephritis, IGA; Humans; Practice Guidelines as Topic; Prednisone
PubMed: 10369196
DOI: 10.1046/j.1523-1755.1999.07008.x -
Targeted Oncology May 2021Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to...
Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry.
BACKGROUND
Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients.
OBJECTIVE
To evaluate the real-world safety and efficacy of AAP as first-line and second-line [post-docetaxel only (AAP-PD)] treatment in patients with mCRPC.
PATIENTS AND METHODS
The Prostate Cancer Registry (PCR) was a prospective, international, observational study of patients with mCRPC in routine clinical practice. Men aged ≥ 18 years with confirmed mCRPC were included. Baseline characteristics, safety (treatment-emergent adverse events, treatment-emergent severe adverse events), and efficacy [progression-free survival (PFS) and overall survival (OS)] were analyzed.
RESULTS
At baseline, patients who received first-line AAP (n = 754) were generally older than patients who received AAP-PD (n = 354); median age was 76 years and 70 years, respectively. However, the rate of visceral metastasis was higher in the AAP-PD cohort than in the AAP cohort (17.7% vs. 9.6%, respectively). Demographics and disease characteristics of patients with baseline cardiovascular disease were similar to those of the overall registry population. Efficacy outcomes were similar for all patients, regardless of the line of AAP therapy. For first-line AAP and AAP-PD, respectively, the median PFS was 8.9 and 5.8 months for all patients and 9.1 and 6.0 months for patients with cardiovascular comorbidities; median OS was 27.1 and 23.4 months for all patients, and 27.4 and 23.1 months for patients with cardiovascular comorbidities. There were no unexpected adverse events in any patient subgroup.
CONCLUSIONS
These real-world data complement the findings from randomized controlled trials, indicating that first- and second-line AAP is well tolerated and effective in patients with mCRPC, including those with underlying CV comorbidities.
TRIAL REGISTRATION NUMBER
NCT02236637, registered 8 September 2014.
Topics: Abiraterone Acetate; Aged; Humans; Male; Prednisone; Prostatic Neoplasms, Castration-Resistant; Registries
PubMed: 33826036
DOI: 10.1007/s11523-021-00807-4 -
European Neurology 2021The aim of the study was to estimate the exacerbation incidence rate (IR) in acetylcholine receptor antibody (AChR)-positive generalized myasthenia gravis (MG) and its...
OBJECTIVE
The aim of the study was to estimate the exacerbation incidence rate (IR) in acetylcholine receptor antibody (AChR)-positive generalized myasthenia gravis (MG) and its predictors.
METHODS
The primary outcome in this retrospective study was to estimate moderate-to-severe (M-S) exacerbations IR in the early course of generalized MG. The secondary outcome was to explore the predictors of MG exacerbations.
RESULTS
Between 1999 and 2015, we identified 78 AChR-positive generalized MG patients and 37 M-S exacerbations over the first 6 years following the onset of generalized MG symptoms. The M-S exacerbation IR was 12.2 per 100 person years (95% confidence interval [CI] 8.8-16.8). Any exacerbation (including mild) IR was 24.4 per 100 person years (95% CI 19.4-30.7). After controlling for confounding factors, MG exacerbation IR predictors included gender, disease severity at onset, and prednisone dose reduction with risk ratio of 0.34 (male gender), 2.67, and 20.8, respectively (all p values <0.05). M-S exacerbation occurred in 25 cases (32.1%), while any exacerbation (mild or M-S) was detected in 45 cases (57.7%).
CONCLUSION
More than half of newly diagnosed AChR + MG cases experience an exacerbation in the first 6 years. Gender, disease severity at onset and prednisone dose reduction are predictors that could inform clinical practice and future research.
Topics: Autoantibodies; Humans; Male; Myasthenia Gravis; Prednisone; Receptors, Cholinergic; Retrospective Studies
PubMed: 33321491
DOI: 10.1159/000512077