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The New Zealand Medical Journal Oct 2017
Topics: Airway Obstruction; Bronchi; Bronchoalveolar Lavage Fluid; Bronchoscopy; Female; Ferrous Compounds; Foreign Bodies; Humans; Middle Aged; Prednisone
PubMed: 29073659
DOI: No ID Found -
The Oncologist May 2015Dexamethasone combined with abiraterone acetate might result in improved survival in the treatment of castration-resistant prostate cancer compared with the Food and...
Dexamethasone combined with abiraterone acetate might result in improved survival in the treatment of castration-resistant prostate cancer compared with the Food and Drug Administration-approved prednisone combination, but the hypothesis must be confirmed with with clinical studies comparing the two combinations.
Topics: Androstenes; Antineoplastic Agents, Hormonal; Humans; Male; Prednisone; Prostatic Neoplasms, Castration-Resistant
PubMed: 25888269
DOI: 10.1634/theoncologist.2015-0010 -
Journal of Clinical Pharmacology Sep 2018To evaluate the steady-state pharmacokinetics of prednisone and its metabolite prednisolone in pregnant and lactating female subjects, 19 subjects received prednisone...
To evaluate the steady-state pharmacokinetics of prednisone and its metabolite prednisolone in pregnant and lactating female subjects, 19 subjects received prednisone (4-40 mg/day orally) in early (n = 3), mid (n = 9), and late (n = 13) pregnancy as well as postpartum with (n = 2) and without (n = 5) lactation. Serial blood and urine samples were collected over 1 dosing interval. Prednisone and its metabolite, prednisolone, steady-state noncompartmental pharmacokinetic parameters were estimated. During pregnancy, prednisone apparent oral clearance increased with dose (35.1 ± 11.4 L/h with 5 mg, 52.6 ± 5.2 L/h with 10 mg, and 64.3 ± 6.9 L/h with 20 mg, P = .001). Similarly, unbound prednisone apparent oral clearance increased with dose. In addition, prednisolone renal clearance increased with dose (0.3 ± 0.3 L/h with 5 mg, 0.5 ± 0.4 L/h with 10 mg, and 1.3 ± 1.1 L/h with 20 mg, P = .002). Higher prednisone (r = 0.57, P ≤ .05) and prednisolone (r = 0.75, P ≤ .05) concentrations led to a higher percentage of unbound drug. Breast-milk/plasma area under the concentration-time curve ratios were 0.5-0.6 for prednisone and 0.02-0.03 for prednisolone. Relative infant doses were 0.35% to 0.53% and 0.09% to 0.18%, for prednisone and prednisolone, respectively. Prednisone and prednisolone exhibit dose- and concentration-dependent pharmacokinetics during pregnancy, and infant exposure to these agents via breast milk is minimal.
Topics: Area Under Curve; Female; Glucocorticoids; Half-Life; Humans; Lactation; Postpartum Period; Prednisone; Pregnancy
PubMed: 29733485
DOI: 10.1002/jcph.1122 -
International Journal of Radiation... Aug 2023Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Radiation pneumonitis (RP) is the most common dose-limiting toxicity for thoracic radiation therapy. Nintedanib is used for the treatment of idiopathic pulmonary fibrosis, which shares pathophysiological pathways with the subacute phase of RP. Our goal was to investigate the efficacy and safety of nintedanib added to a prednisone taper compared with a prednisone taper alone in reducing pulmonary exacerbations in patients with grade 2 or higher (G2+) RP.
METHODS AND MATERIALS
In this phase 2, randomized, double-blinded, placebo-controlled trial, patients with newly diagnosed G2+ RP were randomized 1:1 to nintedanib or placebo in addition to a standard 8-week prednisone taper. The primary endpoint was freedom from pulmonary exacerbations at 1 year. Secondary endpoints included patient-reported outcomes and pulmonary function tests. Kaplan-Meier analysis was used to estimate the probability of freedom from pulmonary exacerbations. The study was closed early due to slow accrual.
RESULTS
Thirty-four patients were enrolled between October 2015 and February 2020. Of 30 evaluable patients, 18 were randomized to the experimental Arm A (nintedanib + prednisone taper) and 12 to the control Arm B (placebo + prednisone taper). Freedom from exacerbation at 1 year was 72% (confidence interval, 54%-96%) in Arm A and 40% (confidence interval, 20%-82%) in Arm B (1-sided, P = .037). In Arm A, there were 16 G2+ adverse events possibly or probably related to treatment compared with 5 in the placebo arm. There were 3 deaths during the study period in Arm A due to cardiac failure, progressive respiratory failure, and pulmonary embolism.
CONCLUSIONS
There was an improvement in pulmonary exacerbations by the addition of nintedanib to a prednisone taper. Further investigation is warranted for the use of nintedanib for the treatment of RP.
Topics: Humans; Protein Kinase Inhibitors; Radiation Pneumonitis; Prednisone; Disease Progression; Double-Blind Method
PubMed: 36889516
DOI: 10.1016/j.ijrobp.2023.02.030 -
Allergy Aug 2023The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The potential benefit of inducing delayed-type hypersensitivity (DTH) reaction in healthy volunteers (HVs) as experimental models to study skin inflammatory disorders was recently reported using bulk molecular technologies. Immunophenotype of skin T cells, including cellular source of Type 1, 2, and 3 cytokines, in a local DTH reaction and their modulation by oral drugs remain to be investigated.
METHOD
Purified protein derivative (PPD), nickel, diphencyprone (DPCP), or house dust mite (HDM) was administered as sensitizer to 40 HVs. In addition, 20 HVs were randomized to receive oral prednisone or placebo before DPCP challenge. We characterized the immunophenotype and cytokine profile of CD3 T cell infiltrate, and examined the modulation by oral prednisone at single-cell level using multiparameter flow cytometry and unsupervised analysis.
RESULTS
PPD was biased toward a Th1 and Tc1 response, and HDM a Th2/Th17 and Tc2. Nickel and DPCP displayed a mixed Th1/Th2/Th17 and Tc1 response. CD4 CD25 FoxP3 regulatory T cells (Tregs), the minor CD4 CD25 FoxP3 ICOS PD-1 (activated PD-1 Th), and CD103 tissue resident memory (TRM) cells were detected in all groups. DPCP uniquely elicited rare CD8 CD103 CD25 RoRγt PD-1 ICOS IFNγ T cells (activated CD8 IFNγ PD-1 TRM). Oral prednisone decreased frequencies of activated PD-1 Th and CD8 IFNγ PD-1 TRM subsets relative to placebo in DPCP reaction. The latter was positively correlated with improvement of clinical parameters with prednisone.
CONCLUSION
DTH and skin CD3 T cell profiles elicited by common sensitizers can be modulated by oral drugs. Corticosteroids reduce the frequencies of activated PD-1 Th and CD8 IFNγ PD-1 TRM cells after DPCP exposure.
Topics: Humans; Prednisone; Programmed Cell Death 1 Receptor; Nickel; Forkhead Transcription Factors
PubMed: 37163280
DOI: 10.1111/all.15764 -
Frontiers in Immunology 2023To describe the clinical predictors and immune-related factors for exacerbation in adults with well-controlled generalized myasthenia gravis (GMG).
OBJECTIVES
To describe the clinical predictors and immune-related factors for exacerbation in adults with well-controlled generalized myasthenia gravis (GMG).
METHODS
We conducted a retrospective analysis of 585 adults with well-controlled GMG from our institution to explore the risk factors for exacerbation. Furthermore, propensity score matching (PSM) was used to compare the proportions of lymphocyte subsets, and the levels of immunoglobulin, complement, and anti-acetylcholine receptor antibody (AChR-ab) in the peripheral blood of 111 patients with exacerbations and 72 patients without exacerbations.
RESULTS
A total of 404 patients (69.1%) experienced at least one exacerbation, and the median (interquartile range) time to the first exacerbation was 1.5 years (0.8-3.1 years). Multivariable Cox regression analysis showed that age at onset, disease duration before enrollment, Myasthenia Gravis Foundation of America classification (MGFA) class III vs. class II, MGFA class IV-V vs. class II, AChR-ab levels, anti-muscle specific kinase antibody levels, thymus hyperplasia, prednisone plus immunosuppressants vs. prednisone treatment, and thymectomy were independent predictors for exacerbations [hazard ratio (HR) = 1.011, 1.031, 1.580, 1.429, 2.007, 2.033, 1.461, 0.798, and 0.651, respectively]. Propensity-matched analysis compared 51 patient pairs. After PSM, the peripheral blood proportions of CD3CD19 B cells, ratios of CD3CD4/CD3CD8 T cells, and AChR-ab levels were significantly increased, and the peripheral blood proportions of CD3CD8 T and CD4CD25CD127 regulatory T cells (Tregs) were significantly lower in patients with exacerbation than in those without exacerbation (all < 0.05).
CONCLUSION
Myasthenia gravis (MG) exacerbations were more frequent in those patients with older onset age, longer disease duration, more severe MGFA classification, positive AChR-ab, and lack of combined immunotherapy or thymectomy treatment. On the other hand, CD3CD19 B cells, CD3CD8 T cells, Tregs, and AChR-ab in peripheral blood may be involved in the course of GMG exacerbation.
Topics: Adult; Humans; Prednisone; Retrospective Studies; CD8-Positive T-Lymphocytes; Myasthenia Gravis; Autoantibodies
PubMed: 37266422
DOI: 10.3389/fimmu.2023.1177249 -
Cleveland Clinic Journal of Medicine Jun 2020Glucocorticoids cause significant bone loss, predominantly affecting trabecular bone, with consequent fragility fractures. The risk of fractures is related to the dose... (Review)
Review
Glucocorticoids cause significant bone loss, predominantly affecting trabecular bone, with consequent fragility fractures. The risk of fractures is related to the dose and duration of glucocorticoid use, but an increased risk may be observed even at low doses and even in the first month of treatment. Steps to prevent or treat osteoporosis should be considered in all patients who take the equivalent of prednisone at a dose of 2.5 mg or more per day for 3 or more months.
Topics: Adult; Bone Density; Cancellous Bone; Drug Administration Schedule; Female; Glucocorticoids; Humans; Male; Middle Aged; Osteoporosis; Osteoporotic Fractures; Prednisone; Risk Factors; Time Factors
PubMed: 32605977
DOI: 10.3949/ccjm.87a.19039 -
Journal of Veterinary Internal Medicine Nov 2022The potential effects of glucocorticoid administration on rivaroxaban's anticoagulant bioactivity in dogs, and an appropriate rivaroxaban dosage regimen for dogs...
BACKGROUND
The potential effects of glucocorticoid administration on rivaroxaban's anticoagulant bioactivity in dogs, and an appropriate rivaroxaban dosage regimen for dogs receiving glucocorticoid therapy are unknown.
HYPOTHESIS/OBJECTIVES
The objective was to determine whether glucocorticoid administration influences the anticoagulant effects of rivaroxaban in healthy dogs. We hypothesized that administration of rivaroxaban and prednisone would reduce the anticoagulant intensity compared with rivaroxaban alone.
ANIMALS
Nine healthy dogs.
METHODS
Randomized, cross-over study. Dogs were administered prednisone (2 mg/kg, PO, q24h), rivaroxaban (1.5 mg/kg, PO, q24h), or prednisone and rivaroxaban, and the coagulation status was evaluated using prothrombin time (PT), and rivaroxaban-calibrated anti-Xa activity (RIVA, results were log transformed for analysis), before drug administration and on days 2, 4, and 8. Linear mixed models and correlation were used to evaluate associations in variables (P < .05 was considered significant).
RESULTS
There were no differences in RIVA results for the rivaroxaban and prednisone/rivaroxaban groups on day 8 (P = .599, median 87 [range 45-156] to 167 [56-333], respectively, median difference 90 ng/mL [95% CI:87.3-161.8]) There was a strong correlation between RIVA and PT results when days 2, 4, and 8 were combined (r = .846, P < .001), and increased during drug administration, day 2 (r = .810, P < .001), day 4 (r = .863, P < .001), and day 8 (r = .885, P < .001).
CONCLUSIONS AND CLINICAL IMPORTANCE
Clotting times in the PT correlate with rivaroxaban levels and may prove useful for drug monitoring. Prednisone administration had no apparent influence on the anticoagulant effects of rivaroxaban in healthy dogs, suggesting that combined therapy will not require dosage adjustments.
Topics: Dogs; Animals; Prednisone; Rivaroxaban; Glucocorticoids; Cross-Over Studies; Anticoagulants
PubMed: 36399000
DOI: 10.1111/jvim.16572 -
Autoimmunity Reviews Jun 2016Relapsing polychondritis (RP) is a rare connective tissue disease in which recurrent bouts of inflammation, involve the cartilage of the ears, nose, larynx,... (Review)
Review
Relapsing polychondritis (RP) is a rare connective tissue disease in which recurrent bouts of inflammation, involve the cartilage of the ears, nose, larynx, tracheobronchial tree and cardiovascular system. RP is generally observed in the fourth and fifth decades of life and occurs with equal frequency in both sexes. The cause of RP is still unknown. It is considered an immune-mediated disease, as there is an overlap between well documented RP with other rheumatic and autoimmune diseases. There is a significant association of RP with the antigen HLA-DR4. RP includes loss of basophilic staining of cartilage matrix perichondral accompanied by inflammation of the cartilage. Cells are present perivascular mononuclear and polymorphonuclear cells infiltrated. The chondrocytes become vacuolated and necrotic and are replaced by fibrous tissue. Common symptoms are often absent in the early stages of the disease in almost half the cases, resulting in delay in diagnosis. The development of chondrite allows the diagnosis of RP in patients initially evaluated for joint abnormalities, ocular, cutaneous, or audio-vestibular. Diagnostic criteria for RP are based on characteristic clinical manifestations. According to Damiani and Levine, the diagnosis can be considered final when one or more of the clinical features are present in conjunction with biopsy confirmation. The course of symptoms for patients with relapsing polychondritis is often unpredictable. Patients with mild signs of acute inflammation are usually treated with non-steroidal anti-inflammatory drugs and small doses of prednisone. Patients with severe manifestations, such as airway compromise may require high doses of prednisone or even intravenous pulse methyl-prednisone.
Topics: Autoimmune Diseases; Humans; Polychondritis, Relapsing; Prednisone
PubMed: 26876384
DOI: 10.1016/j.autrev.2016.02.013 -
Lancet (London, England) Jul 2020Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised... (Comparative Study)
Comparative Study Randomized Controlled Trial
Continuing versus tapering glucocorticoids after achievement of low disease activity or remission in rheumatoid arthritis (SEMIRA): a double-blind, multicentre, randomised controlled trial.
BACKGROUND
Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis.
METHODS
The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012.
FINDINGS
Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency.
INTERPRETATION
In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose.
FUNDING
F Hoffmann-La Roche.
Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Antibodies, Monoclonal, Humanized; Arthritis, Rheumatoid; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; France; Germany; Glucocorticoids; Humans; Injections, Subcutaneous; Italy; Male; Middle Aged; Outcome Assessment, Health Care; Prednisone; Remission Induction; Russia; Serbia; Tunisia
PubMed: 32711802
DOI: 10.1016/S0140-6736(20)30636-X