Browsing by Subject "Prednisone"

Now showing 1 - 4 of 4
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    Design of a multicenter randomized clinical trial for treatment of Alcohol-Associated Hepatitis
    (Elsevier, 2023-01-18) Tu, Wanzhu; Gawrieh, Samer; Dasarathy, Srinivasan; Mitchell, Mack C.; Simonetto, Douglas A.; Patidar, Kavish R.; McClain, Craig J.; Bataller, Ramon; Szabo, Gyongyi; Tang, Qing; Barton, Bruce A.; Radaeva, Svetlana; Sanyal, Arun J.; Shah, Vijay; Alcoholic Hepatitis Network (AlcHepNet) Investigators; Biostatistics, School of Public Health
    Background: Mortality is high for severe alcohol-associated hepatitis (AH). Corticosteroids are the standard of care for patients without contraindications. Recent data showed that interleukin-1β receptor antagonist anakinra attenuated inflammation and liver damage. We designed a multicenter, double-blind, randomized controlled trial to assess the safety and efficacy of anakinra compared to prednisone. Methods: Patients meeting the clinical and biochemical criteria for severe AH with MELD scores between 20 and 35 were recruited at eight clinical sites. Eligible patients enrolled in the study were randomized to anakinra, 100 mg subcutaneous injection for 14 days, plus zinc sulfate 220 mg for 90 days, vs. prednisone 40 mg PO daily for 30 days. Matching placebos for anakinra, zinc, and prednisone were provided to mask the treatment. Participants were followed for 180 days. The primary outcome was overall survival at 90 days. An unadjusted log-rank test was used to compare the survival of the two treatments in the first 90 days. Between July 10, 2020, and March 4, 2022, we screened 1082 patients with severe AH, and 147 eligible patients were enrolled and randomized. The average baseline MELD score was 25 [range 20-35], Maddrey discriminant function (MDF) was 59.4 [range 20.2-197.5]. The mean aspartate transaminase (AST)-to-alanine transaminase (ALT) ratio was 3.5. The baseline characteristics were not statistically different between the two treatment groups. Conclusions: The study provided a direct comparison of the survival benefits and safety profiles of anakinra plus zinc vs. prednisone in patients with severe AH.
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    Differential effects of hydrocortisone, prednisone, and dexamethasone on hormonal and pharmacokinetic profiles: a pilot study in children with congenital adrenal hyperplasia
    (BioMed Central, 2016) Nebesio, Todd D.; Renbarger, Jamie L.; Nabhan, Zeina M.; Ross, Sydney E.; Slaven, James E.; Li, Lang; Walvoord, Emily C.; Eugster, Erica A.; Department of Pediatrics, IU School of Medicine
    BACKGROUND: Little is known about the comparative effects of different glucocorticoids on the adrenal and growth hormone (GH) axes in children with congenital adrenal hyperplasia (CAH). We sought to compare the effects of hydrocortisone (HC), prednisone (PDN), and dexamethasone (DEX) in children with classic CAH and to investigate a potential role of pharmacogenetics. METHODS: Subjects were randomly assigned to three sequential 6-week courses of HC, PDN, and DEX, each followed by evaluation of adrenal hormones, IGF-1, GH, and body mass index (BMI). Single nucleotide polymorphism (SNP) analysis of genes in the glucocorticoid pathway was also performed. RESULTS: Nine prepubertal subjects aged 8.1 ± 2.3 years completed the study. Mean ACTH, androstenedione, and 17-hydroxyprogesterone (17-OHP) values were lower following the DEX arm of the study than after subjects received HC (p ≤ 0.016) or PDN (p ≤ 0.002). 17-OHP was also lower after HC than PDN (p < 0.001). There was no difference in IGF-1, GH, or change in BMI. SNP analysis revealed significant associations between hormone concentrations, pharmacokinetic parameters, and variants in several glucocorticoid pathway genes (ABCB1, NR3C1, IP013, GLCCI1). CONCLUSIONS: DEX resulted in marked adrenal suppression suggesting that its potency relative to hydrocortisone and prednisone was underestimated. SNPs conferred significant differences in responses between subjects. Although preliminary, these pilot data suggest that incorporating pharmacogenetics has the potential to eventually lead to targeted therapy in children with CAH.
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    Enhancing Prednisone-Based Arthritis Therapy with Targeted IL-27 Gene Delivery
    (MDPI, 2022-06-09) Marin, Adriana A.; Decker, Richard E.; Kumar, Shreya; Lamantia, Zachary; Yokota, Hiroki; Emrick, Todd; Figueiredo, Marxa L.; Biomedical Engineering, School of Engineering and Technology
    Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized primarily by synovial hyperplasia and accumulation of several types of immune infiltrates that promote progressive destruction of the articular structure. Glucocorticoids are often prescribed to treat RA because of their strong anti-inflammatory and immunosuppressive effects. However, their application must be limited to the short-term due to a risk of adverse events. In the present study, we examined the potential combination of low-dose prednisone with gene delivery of an agent of promising and complementary effectiveness in RA, interleukin (IL)-27. IL-27 has been shown to have anti-inflammatory potential, while also acting as an effective bone-normalization agent in prior reports. The present report examined a version of IL-27 targeted at the C-terminus with a short 'peptide L' (pepL, LSLITRL) that binds the interleukin 6 receptor α (IL-6Rα) upregulated during inflammation. By focusing on this targeted form, IL-27pepL or 27pL, we examined whether the anti-inflammatory potential of prednisone (at a relatively low dose and short duration) could be further enhanced in the presence of 27pL as a therapy adjuvant. Our results indicate that 27pL represents a novel tool for use as an adjuvant with current therapeutics, such as prednisone, against inflammatory conditions.
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    Long-term effect of thymectomy in patients with non-thymomatous myasthenia gravis treated with prednisone: 2-year extension of the MGTX randomised tria
    (Elsevier, 2019-03) Wolfe, Gil I.; Kaminski, Henry J.; Aban, Inmaculada B.; Minisman, Greg; Kuo, Hui-Chien; Marx, Alexander; Ströbel, Philipp; Mazia, Claudio; Oger, Joel; Cea, J. Gabriel; Heckmann, Jeannine M.; Evoli, Amelia; Nix, Wilfred; Ciafaloni, Emma; Antonini, Giovanni; Witoonpanich, Rawiphan; King, John O.; Beydoun, Said R.; Chalk, Colin H.; Barboi, Alexandru C.; Amato, Anthony A.; Shaibani, Aziz I.; Katirji, Bashar; Lecky, Bryan R. F.; Buckley, Camilla; Vincent, Angela; Dias-Tosta, Elza; Yoshikawa, Hiroaki; Waddington-Cruz, Márcia; Pulley, Michael T.; Rivner, Michael H.; Kostera-Pruszczyk, Anna; Pascuzzi, Robert M.; Jackson, Carlayne E.; Verschuuren, Jan J. G. M.; Massey, Janice M.; Kissel, John T.; Werneck, Lineu C.; Benatar, Michael; Barohn, Richard J.; Tandan, Rup; Mozaffar, Tahseen; Silvestri, Nicholas J.; Conwit, Robin; Sonett, Joshua R.; Jaretzki, Alfred, III; Newsom-Davis, John; Cutter, Gary R.; Neurology, School of Medicine
    Background: The MGTX trial demonstrated that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status measured by the Quantitative MG (QMG) score in patients with non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events. Methods: A multicentre, rater-blinded 2-year extension study was conducted across 36 centres in 15 countries for patients who completed the MGTX randomised, controlled trial and were willing to participate. MGTX trial patients were aged 18 to 65 years at enrollment, had generalised non-thymomatous myasthenia gravis (MG) with disease duration less than 5 years and elevated (≥1.00 nmol/l; 0.50–0.99 nmol/l allowed if confirmed by positive edrophonium or electrophysiologic testing) acetylcholine receptor antibody titers.. All patients received oral prednisone at doses titrated up to 100 mg on alternate days until they achieved minimal manifestation status. The primary endpoints were the time-weighted average of both the QMG and alternate-day prednisone dose from month 0 to month 60. Analyses were by intention-to-treat. The trial was registered on clinicaltrials.gov, number NCT00294658. Findings: Of 111 subjects who completed the 3-year MGTX trial, 68 (61%) entered the extension study between September 1, 2009 and August 26, 2015 (33 prednisone alone; 35 prednisone plus thymectomy). Of the 68, 50 (74%) completed the 60-month assessment (24 prednisone alone; 26 prednisone plus thymectomy). At 5 years, patients randomised to thymectomy plus prednisone continued to demonstrate improved clinical status compared to patients in the prednisone alone group based on time-weighted average QMG (5.47±3.87 vs. 9.34±5.08; 95% CI for the difference 0.71–7.04; p=0.0007) and lower average alternate-day prednisone requirements (24 mg±21 mg vs. 48±29 mg; 95% CI for the difference 12–36 mg; p=0.0002). The proportion of patients requiring hospitalisation for MG exacerbation (6% vs. 30%; 95% CI for the difference 7.1–42.1%; p=0.0105) was lower in the thymectomy group. Other MEDRA-coded adverse events were infrequent, occurring at a rate of ≤6% in both groups and did not differ significantly between them. There were no treatment-related deaths. Interpretation: After 5 years, thymectomy continues to confer benefits in generalised non-thymomatous MG. Although caution in predicting benefit for all such patients is appropriate since the extension study included only half of MGTX trial subjects, results available through month 60 provide further evidence to support thymectomy in this large group of patients with generalised MG.