Acute serum protein and cytokine response of single dose of prednisone in adult volunteers

Roy, Runia; Soldin, Steven J.; Stolze, Brian; Barbieri, Marissa; Tawalbeh, Shefa M.; Rouhana, Nicole; Fronczek, Ann E.; Nagaraju, Kanneboyina; Anker, John van den; Dang, Utkarsh J.; Hoffman, Eric P.

doi:10.1016/j.steroids.2021.108953

Cited by 4 publications

(3 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Corticosteroid drugs (and endogenous cortisol) potently, broadly, and acutely inhibit the hypothalamic-pituitary-adrenal (HPA) axis, and long-term use can lead to adrenal insufficiency . In this trial, boys with DMD showed an unexpected high incidence of adrenal insufficiency at baseline by both ACTH-stimulation and morning cortisol measures.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy

et al. 2022

Self Cite

View full text Add to dashboard Cite

IMPORTANCECorticosteroidal anti-inflammatory drugs are widely prescribed but long-term use shows adverse effects that detract from patient quality of life.OBJECTIVE To determine if vamorolone, a structurally unique dissociative steroidal anti-inflammatory drug, is able to retain efficacy while reducing safety concerns with use in Duchenne muscular dystrophy (DMD).DESIGN, SETTING, AND PARTICIPANTS Randomized, double-blind, placebo-and prednisone-controlled 24-week clinical trial, conducted from June 29, 2018, to February 24, 2021, with 24 weeks of follow-up. This was a multicenter study (33 referral centers in 11 countries) and included boys 4 to younger than 7 years of age with genetically confirmed DMD not previously treated with corticosteroids. INTERVENTIONSThe study included 4 groups: placebo; prednisone, 0.75 mg/kg per day; vamorolone, 2 mg/kg per day; and vamorolone, 6 mg/kg per day. MAIN OUTCOMES AND MEASURESStudy outcomes monitored (1) efficacy, which included motor outcomes (primary: time to stand from supine velocity in the vamorolone, 6 mg/kg per day, group vs placebo; secondary: time to stand from supine velocity [vamorolone, 2 mg/kg per day], 6-minute walk distance, time to run/walk 10 m [vamorolone, 2 and 6 mg/kg per day]; exploratory: NorthStar Ambulatory Assessment, time to climb 4 stairs) and (2) safety, which included growth, bone biomarkers, and a corticotropin (ACTH)-challenge test.RESULTS Among the 133 boys with DMD enrolled in the study (mean [SD] age, 5.4 [0.9] years), 121 were randomly assigned to treatment groups, and 114 completed the 24-week treatment period. The trial met the primary end point for change from baseline to week 24 time to stand velocity for vamorolone, 6 mg/kg per day (least-squares mean [SE] velocity, 0.05 [0.01] m/s vs placebo −0.01 [0.01] m/s; 95% CI, 0.02-0.10; P = .002) and the first 4 sequential secondary end points: time to stand velocity, vamorolone, 2 mg/kg per day, vs placebo; 6-minute walk test, vamorolone, 6 mg/kg per day, vs placebo; 6-minute walk test, vamorolone, 2 mg/kg per day, vs placebo; and time to run/walk 10 m velocity, vamorolone, 6 mg/kg per day, vs placebo. Height percentile declined in prednisone-treated (not vamorolone-treated) participants (change from baseline [SD]: prednisone, −1.88 [8.81] percentile vs vamorolone, 6 mg/kg per day, +3.86 [6.16] percentile; P = .02). Bone turnover markers declined with prednisone but not with vamorolone. Boys with DMD at baseline showed low ACTH-stimulated cortisol and high incidence of adrenal insufficiency. All 3 treatment groups led to increased adrenal insufficiency. CONCLUSIONS AND RELEVANCEIn this pivotal randomized clinical trial, vamorolone was shown to be effective and safe in the treatment of boys with DMD over a 24-week treatment period. Vamorolone may be a safer alternative than prednisone in this disease, in which long-term corticosteroid use is the standard of care.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The favorable bone biomarker profile observed in the vamorolone-treated groups compared with corticosteroids is explained by vamorolone not being a substrate for 11β-hydroxysteroid dehydrogenase enzymes which are necessary for corticosteroid-induced bone morbidities in mice, as it lacks the 11βmoiety acted upon by these enzymes ( 36 , 37 ). Additionally, Guglieri et al incidentally found an unexpectedly high incidence of adrenal insufficiency at baseline in boys with DMD in both vamorolone-treated and corticosteroids-treated groups using both ACTH-stimulation and morning cortisol measurements, as corticosteroid medications (including endogenous cortisol) potently, widely, and rapidly block the hypothalamic-pituitary-adrenal (HPA) axis and long-term use can result in adrenal insufficiency ( 38 ), this finding with the vamorolone-treated group requires additional investigation.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis

et al. 2023

View full text Add to dashboard Cite

Background and aimRecent studies evaluated the role of vamorolone in treating Duchenne muscular dystrophy (DMD), so we aimed in our Meta-analysis to assess the efficacy of vamorolone in comparison with placebo and corticosteroids for treating DMD patients.MethodsWe searched PubMed, Web of Science, Scopus, and Cochrane library databases. We included any randomized control trials and controlled observational studies that investigated the role of vamorolone in treating DMD patients. We used RevMan software, version 5.4. to perform our meta-analysis.ResultsAfter a search of the literature, 4 studies were included in the meta-analysis; the total number of patients included in the study is 277 patients, 125 patients in the vamorolone group, 106 in the glucocorticoids group, and 46 in placebo (steroid naïve) group. The pooled analysis showed a statistically significant association between the vamorolone group and increased TTSTAND velocity, TTRW velocity and TTCLIMB velocity compared with the placebo group (MD = 0.04, 95% CI = 0.02–0.07, p = 0.002), (MD = 0.24, 95% CI = 0.11–0.37, p = 0.0003), and (MD = 0.06, 95% CI = 0.05–0.06, p < 0.00001), respectively. Also, the analysis showed a statistically significant association between vamorolone and increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid group (MD = −0.14, 95% CI = −0.26 to −0.01, p = 0.03) and (MD = 17.82, 95% CI = 3.89–31.75, p = 0.01), respectively.ConclusionOur study revealed a significant association between vamorolone and increased TTSTAND velocity, TTRW velocity, and TTCLIMB velocity compared with the placebo (steroid naïve), also showed a statistically significant association between increased TTRW velocity and increased Height percentile for age compared with the glucocorticoid that enhances the privilege of vamorolone over glucocorticoid in treating DMD patients. More multicenter randomized studies are needed to support our results.

show abstract

“…The biomarker utility of cytokines is inherently limited as these molecules also mediate inflammation brought about by infection or tissue damage, and their systemic levels could be affected by corticosteroid therapy [ 64 ]. Indeed, there were moderate correlations between CRP, IL-6 and IL-10 in our dataset which possibly confounded data interpretation.…”

Section: Discussionmentioning

confidence: 99%

Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma

et al. 2023

View full text Add to dashboard Cite

Background Detection of circulating tumour DNA (ctDNA) in biological fluids is a minimally invasive alternative to tissue biopsy for therapy monitoring. Cytokines are released in the tumour microenvironment to influence inflammation and tumorigenic mechanisms. Here, we investigated the potential biomarker utility of circulating cytokines vis-à-vis ctDNA in ALK-rearranged+ lung adenocarcinoma (ALK + NSCLC) and explored the optimal combination of molecular parameters that could indicate disease progression. Methods Longitudinal serum samples (n = 296) were collected from ALK + NSCLC patients (n = 38) under tyrosine kinase inhibitor (TKI) therapy and assayed to quantify eight cytokines: IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12p70, MCP1 and TNF-α. Generalised linear mixed-effect modelling was performed to test the performance of different combinations of cytokines and previously determined ctDNA parameters in identifying progressive disease. Results Serum IL-6, IL-8 and IL-10 were elevated at progressive disease, with IL-8 having the most significant impact as a biomarker. Integrating changes in IL-8 with ctDNA parameters maximised the performance of the classifiers in identifying disease progression, but this did not significantly outperform the model based on ctDNA alone. Conclusions Serum cytokine levels are potential disease progression markers in ALK + NSCLC. Further validation in a larger and prospective cohort is necessary to determine whether the addition of cytokine evaluation could improve current tumour monitoring modalities in the clinical setting.

show abstract

Acute serum protein and cytokine response of single dose of prednisone in adult volunteers

Cited by 4 publications

References 31 publications

Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy

Efficacy and Safety of Vamorolone vs Placebo and Prednisone Among Boys With Duchenne Muscular Dystrophy

Efficacy of vamorolone in treatment of Duchene muscle dystrophy. A meta-analysis

Integrated circulating tumour DNA and cytokine analysis for therapy monitoring of ALK-rearranged lung adenocarcinoma

Contact Info

Product

Resources

About