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Clinical Rheumatology Mar 2024To investigate the relation between cumulative intravenous methylprednisolone dose and disease activity, damage, and mortality among a group of Egyptian SLE patients.
Cumulative pulse methylprednisolone and its relation to disease activity, damage and mortality in systemic lupus erythematosus patients: A post hoc analysis of COMOSLE-EGYPT study.
OBJECTIVE
To investigate the relation between cumulative intravenous methylprednisolone dose and disease activity, damage, and mortality among a group of Egyptian SLE patients.
PATIENTS AND METHODS
This is a post hoc analysis of a retrospective multicenter COMOSLE study. Cumulative pulse methylprednisolone dose was abstracted from COMOSLE database. Patients with cumulative pulse dose of ≤ 3.0 g (median dose) were compared to those with cumulative dose of > 3.0 g regarding demographic data, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and The Systemic Lupus International Collaborating Clinics/ACR Damage Index (SLICC) score as well as treatment received. Additionally, at 1.5, 3, 6, and 9 g of cumulative methylprednisolone, patients were compared regarding SLICC score and risk of mortality.
RESULTS
Patients who received > 3 g of methylprednisolone were statistically significantly younger at disease onset, had longer disease duration, higher SLEDAI score at last visit, and higher SLICC score (p = 003, p = 0.002, p = 0.004 and p = < 0.001, respectively). Additionally, with every gram increase in the cumulative methylprednisolone, there was a significant increase in SLICC score by 0.169 (B = 0.169, CI = 0.122-0.216, p-value = < 0.001) and an increased risk of mortality by 13.5% (hazard ratio (HR) = 1.135, CI = 1.091-1.180, p-value = 0.001). The best cutoff value of methylprednisolone dose at which damage may occur, ranged between 2.75 (with sensitivity of 81.4% and specificity of 33.9%) and 3.25 g (with sensitivity of 48.3% and specificity of 71.5%).
CONCLUSION
With every gram increase in the cumulative methylprednisolone, there may be increase in damage and mortality, especially in doses exceeding the range of 2.75-3.25 g. Key Points • Treatment of systemic lupus erythematosus should be with the least possible dose of steroids to decrease the risk of damage and mortality. • With every gram increase in the cumulative intravenous methylprednisolone there may be increase in damage and mortality.
Topics: Humans; Egypt; Methylprednisolone; Lupus Erythematosus, Systemic; Retrospective Studies; Severity of Illness Index
PubMed: 38198114
DOI: 10.1007/s10067-023-06858-4 -
The Journal of Pharmacology and... Aug 2019Methylprednisolone (MPL), a corticosteroid of intermediate potency, remains an important immunomodulatory agent for autoimmune diseases. Although sex differences in...
Methylprednisolone (MPL), a corticosteroid of intermediate potency, remains an important immunomodulatory agent for autoimmune diseases. Although sex differences in corticosteroid pharmacokinetics/pharmacodynamics (PK/PD) have been documented in humans, comprehensive preclinical assessments of such differences have not been conducted. Limited in vitro evidence indicates possible sex differences in corticosteroid PK and PD. Therefore, it is hypothesized that comparative PK/PD assessments of MPL disposition and selected PD actions in both sexes will provide insights into factors controlling sex differences in steroid responses. This report focused on the plasma and tissue pharmacokinetics of MPL and its adrenal suppressive effects. Because time-dependent (estrous) regulation of sex hormones in females can influence drug responses, female rats were studied in the proestrus (high estradiol/progesterone) and estrus (low estradiol/progesterone) phases of the reproductive cycle. Cohorts of male and female rats were given a 50 mg/kg bolus dose of MPL intramuscularly. Plasma and liver concentrations of MPL as well as plasma corticosterone concentrations were assayed using high-performance liquid chromatography. An enhanced minimal physiologically-based PK/PD model was developed to characterize MPL kinetics and corticosterone dynamics. The clearance of MPL was ∼3-fold higher in males compared with females, regardless of estrous phase, likely attributable to sex-specific hepatic metabolism in males. Strong inhibitory effects on adrenal suppression were observed in all animals. These temporal steroid profiles in plasma and tissues will be used to drive receptor/gene-mediated PD effects of MPL in both sexes, as described in a companion article (Part III). SIGNIFICANCE STATEMENT: Sex is a relevant factor influencing the pharmacokinetics (PK) and pharmacodynamics (PD) of drugs. Few preclinical PK/PD studies, however, include sex as a variable. Sex differences in the PK and adrenal suppressive effects of the synthetic corticosteroid, methylprednisolone, were assessed in male and female rats as a function of the 4-day rodent reproductive cycle. Drug exposure was 3-fold higher in females, regardless of estrous stage, compared with males. An extended minimal physiologically-based PK/PD model utilizing in vitro and in vivo measurements was developed and applied. These studies provide a framework to account for sex-dependent variability in drug and endogenous agonist (corticosterone) exposures, serving as a prelude to more intricate assessments of sex-related variability in receptor/gene-mediated PD corticosteroid actions.
Topics: Animals; Corticosterone; Female; Male; Methylprednisolone; Models, Biological; Rats; Rats, Wistar; Sex Characteristics
PubMed: 31197019
DOI: 10.1124/jpet.119.257527 -
European Review For Medical and... Jun 2022Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and... (Observational Study)
Observational Study
OBJECTIVE
Methylprednisolone is commonly used to attenuate the cytokine storm and prevent mortality in COVID-19 pneumonia. However, the optimal methylprednisolone dose and duration are unclear. Additional data are required on the effectiveness of methylprednisolone in reducing mortality in COVID-19. This real-life retrospective study aimed to analyze the data of a COVID-19 dedicated ICU and compare the mortality rates of standard care, low-dose, and pulse-dose methylprednisolone in patients requiring mechanical ventilatory support.
PATIENTS AND METHODS
Methylprednisolone's indication, dose, and duration were determined according to the severity of COVID-19 pneumonia based on the patient's demographic parameters, comorbidities, laboratory data, radiology, and arterial blood gas analysis results. 867 patients were grouped as: no methylprednisolone (standard care), low-dose (0.5-1 mg/kg/day) methylprednisolone or pulse-dose (250-1,000 mg/day) methylprednisolone.
RESULTS
The overall mortality rate was 63.78%. Adjusting the dose of methylprednisolone according to the severity of the disease resulted in statistically similar mortality rates despite the increase in disease severity. Mortality was 62.71% in standard treatment, 65.76% in low-dose, and 62.10% in pulse-dose methylprednisolone groups (p = 0.633). Invasive mechanical ventilation at admission was associated with increased mortality (HR: 1.826 [95% CI: 1.542-2.161]; p < 0.001). Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were also associated with mortality.
CONCLUSIONS
Personalizing the dose and duration of methylprednisolone according to the patient's disease severity assessed with demographic, clinical, and laboratory results may benefit mortality in severe COVID-19 patients receiving ventilatory support in the ICU. Hematologic disorders and malignancies, arterial blood pH and HCO3, neutrophil count, and NLR at admission were associated with mortality in our patient cohort.
Topics: Critical Illness; Hospital Mortality; Humans; Intensive Care Units; Methylprednisolone; Neoplasms; Retrospective Studies; COVID-19 Drug Treatment
PubMed: 35776051
DOI: 10.26355/eurrev_202206_29089 -
Frontiers in Immunology 2022In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this...
In contrast to dexamethasone, the clinical efficacy of methylprednisolone (MP) remains controversial, and a systems biology study on its mechanism is lacking. In this study, a total of 38 severe COVID-19 patients were included. The demographics, clinical characteristics, and severity biomarkers including C-reactive protein (CRP), d-dimer, albumin, and Krebs von den Lungen 6 of patients receiving MP (n=26, 40 mg or 80 mg daily for 3-5 days) and supportive therapy (n=12) were compared. Longitudinal measurements of 92 cytokines in MP group from admission to over six months after discharge were performed by multiplex Proximity Extension Assay. The results showed that demographics, baseline clinical characteristics were similar in MP and non-MP groups. No death occurred and the hospital stays between the two groups were similar. Kinetics studies showed that MP was not better than supportive therapy at improving the four severity biomarkers. Cytokines in MP group were characterized by five clusters according to their baseline levels and responses to MP. The immunological feature of severe COVID-19 could be defined by the "core signature" cytokines in cluster 2: MCP-3, IL-6, IFN-γ, and CXCL10, which strongly correlated with each other and CRP, and are involved in cytokine release storm. The "core signature" cytokines were significantly upregulated at baseline and remained markedly elevated after MP treatment. Our work showed a short course of MP therapy could not rapidly improve the immune disorders among severe COVID-19 patients or clinical outcomes, also confirmed "core signature" cytokines, as severity biomarkers similar to CRP, could be applied to evaluate clinical treatment effect.
Topics: Biomarkers; C-Reactive Protein; Cytokine Release Syndrome; Cytokines; Humans; Kinetics; Methylprednisolone; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35350784
DOI: 10.3389/fimmu.2022.758946 -
British Medical Journal Oct 1980
Clinical Trial
Topics: Bronchitis; Clinical Trials as Topic; Forced Expiratory Volume; Humans; Methylprednisolone; Prednisolone
PubMed: 7000290
DOI: No ID Found -
Medicine Sep 2019This study will systematically investigate the efficacy and safety of methylprednisolone for treatment of persistent vertigo (PV).
BACKGROUND
This study will systematically investigate the efficacy and safety of methylprednisolone for treatment of persistent vertigo (PV).
METHODS
All following electronic databases will be searched from inception to the June 30, 2019 without language restrictions: MEDILINE, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database. All randomized controlled trials focusing on assessing the efficacy and safety of methylprednisolone for patients with PV will be fully considered for inclusion. Cochrane risk of bias tool will be used for assessing methodological quality, and RevMan 5.3 software (Cochrane Community, London, UK) will be utilized for statistical analysis.
RESULTS
This study will assess the efficacy and safety of methylprednisolone for PV via assessing primary outcome of vertigo, and secondary outcomes of somatization, depression, anxiety, health-related quality of life, and adverse events.
CONCLUSION
This study will provide a high-quality evidence to judge whether methylprednisolone is an effective and safety therapy for patients with PV.
DISSEMINATION AND ETHICS
No individual data will be utilized in this study, thus, it does not need ethical approval. The results of this study will be published at peer-reviewed journals.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019138890.
Topics: Glucocorticoids; Humans; Methylprednisolone; Treatment Outcome; Vertigo
PubMed: 31567966
DOI: 10.1097/MD.0000000000017194 -
Annals of Internal Medicine Dec 2012
Topics: Anti-Inflammatory Agents; Disease Outbreaks; Drug Compounding; Drug Contamination; Humans; Iatrogenic Disease; Injections, Epidural; Meningitis, Fungal; Methylprednisolone; Methylprednisolone Acetate; United States
PubMed: 23080380
DOI: 10.7326/0003-4819-157-11-201212040-00558 -
JAMA Network Open Oct 2021Local steroid injection is commonly used in treating patients with idiopathic carpal tunnel syndrome, but evidence regarding long-term efficacy is lacking. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Local steroid injection is commonly used in treating patients with idiopathic carpal tunnel syndrome, but evidence regarding long-term efficacy is lacking.
OBJECTIVE
To assess the long-term treatment effects of local steroid injection for carpal tunnel syndrome.
DESIGN, SETTING, AND PARTICIPANTS
This exploratory 5-year extended follow-up of a double-blind, placebo-controlled randomized clinical trial was conducted from November 2008 to March 2012 at a university hospital orthopedic department. Participants included patients aged 22 to 69 years with primary idiopathic carpal tunnel syndrome and no prior treatment with local steroid injections. Data were analyzed from May 2018 to August 2018.
INTERVENTIONS
Patients were randomized to injection of 80 mg methylprednisolone, 40 mg methylprednisolone, or saline.
MAIN OUTCOMES AND MEASURES
The coprimary outcomes were the symptom severity score and rate of subsequent carpal tunnel release surgery on the study hand at 5 years. Secondary outcomes were time from injection to surgical treatment, SF-36 bodily pain score, and score on the 11-item disabilities of the arm, shoulder, and hand scale.
RESULTS
A total of 111 participants (mean [SD] age at follow-up, 52.9 [11.6] years; 81 [73.0%] women and 30 [27.0%] men) were randomized, with 37 in the 80 mg methylprednisolone group, 37 in the 40 mg methylprednisolone group, and 37 in the saline placebo group. Complete 5-year follow-up data were obtained from all 111 participants with no dropouts (100% follow-up). At baseline, mean (SD) symptom severity scores were 2.93 (0.85) in the 80 mg methylprednisolone group, 3.13 (0.70) in the 40 mg methylprednisolone group, and 3.18 (0.75) in the placebo group, and at the 5-year follow up, mean (SD) symptom severity scores were 1.51 (0.66) in the 80 mg methylprednisolone group, 1.59 (0.63) in the 40 mg methylprednisolone group, and 1.67 (0.74) in the placebo group. Compared with placebo, there was no significant difference in mean change in symptom severity score from baseline to 5 years for the 80 mg methylprednisolone group (0.14 [95%CI, -0.17 to 0.45]) or the 40 mg methylprednisolone group (0.12 [95%CI, -0.19 to 0.43]). After injection, subsequent surgical treatment on the study hand was performed in 31 participants (83.8%) in the 80 mg methylprednisolone group, 34 participants (91.9%) in the 40 mg methylprednisolone group, and 36 participants (97.3%) in the placebo group; the number of participants who underwent surgical treatment between the 1-year and 5-year follow-ups was 4 participants (10.8%) in the 80 mg methylprednisolone group, 4 participants (10.8%) in the 40 mg methylprednisolone group, and 2 participants (5.4%) in the placebo group. All surgical procedures were conducted while participants and investigators were blinded to type of injection received. The mean (SD) time from injection to surgery was 180 (121) days in the 80 mg methylprednisolone group, 185 (125) days in the 40 mg methylprednisolone group, and 121 (88) days in the placebo group. Kaplan-Meier survival curves showed statistically significant difference in time to surgical treatment (log-rank test: 80 mg methylprednisolone vs placebo, P = .002 ; 40 mg methylprednisolone vs placebo, P = .02; methylprednisolone 80 mg vs 40 mg, P = .37).
CONCLUSIONS AND RELEVANCE
These findings suggest that in idiopathic carpal tunnel syndrome, local methylprednisolone injection resulted in statistically significant reduction in surgery rates and delay in need for surgery.
TRIAL REGISTRATION
ClinicalTrials.gov Identifiers: NCT00806871 and NCT02652390.
Topics: Adult; Aged; Anti-Inflammatory Agents; Carpal Tunnel Syndrome; Female; Follow-Up Studies; Humans; Injections; Kaplan-Meier Estimate; Male; Methylprednisolone; Middle Aged; Outcome Assessment, Health Care; Young Adult
PubMed: 34677593
DOI: 10.1001/jamanetworkopen.2021.30753 -
Turkish Journal of Medical Sciences Oct 2021Acute lung injury (ALI) is a major cause of death in the intensive care unit. Lipopolysaccharide (LPS) induced lung injury is the most widely used experimental ALI model...
BACKGROUND
Acute lung injury (ALI) is a major cause of death in the intensive care unit. Lipopolysaccharide (LPS) induced lung injury is the most widely used experimental ALI model and provides opportunities for new targeting therapy. In this study, we investigated the effects of tocilizumab, adalimumab, and methylprednisolone in LPS-induced acute lung injury.
METHODS
Lung injury was established by intratracheal instillation of LPS. The rats were randomly divided into six groups: LPS, control, and treatment groups (adalimumab, tocilizumab, methylprednisolone, adalimumab + tocilizumab). Bronchoalveolar lavage (BAL) and lung tissues were collected at 48 h and 96 h following LPS administration from each group. For histological analysis, hematoxylin-eosin (H&E) staining was performed. The sections were obtained for immunohistochemical analysis. IL-6 and TNF-alpha immunoreactivity were measured.
RESULTS
Intratracheal LPS application resulted in inflammatory cell infiltration of interstitial and alveolar spaces and thickening of the alveolar wall. All treatment groups showed significantly amelioration compared to LPS at 48 h. Interestingly, adalimumab and adalimumab + tocilizumab groups showed a significant amelioration of the lung histoarchitecture, compared to the prednisolone group at 96 h (p = 0.028, p = 0.025, respectively). Compared to the control group, LPS stimulation resulted in a significant increase in IL-6 and TNF-alpha immunoreactivity (p < 0.001). IL-6 and TNF-alpha expression were markedly reduced in all treatment groups at 48 h but the reduction was greater in the adalimumab and tocilizumab group than in the steroid. Administration with adalimumab and/or tocilizumab effectively decreased expression of TNF-alpha (p = 0.001) and IL-6 (p < 0.001) at 96 h, but prednisolone did not exert an effective decrease (p > 0.05).
DISCUSSION
Adalimumab and/or tocilizumab significantly reduce the release of proinflammatory cytokines and improve the tissue inflammation in the experimental model of ALI. Our results suggest that adalimumab and/or tocilizumab have a more potent antiinflammatory effect on lung injury than the steroid.
Topics: Animals; Rats; Adalimumab; Lipopolysaccharides; Tumor Necrosis Factor-alpha; Interleukin-6; Steroids; Acute Lung Injury; Methylprednisolone
PubMed: 34217170
DOI: 10.3906/sag-2010-303 -
Journal of Neurotrauma Mar 2016Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of... (Meta-Analysis)
Meta-Analysis Review
Previous meta-analyses of methylprednisolone (MPS) for patients with acute traumatic spinal cord injuries (TSCIs) have not addressed confidence in the quality of evidence used for pooled effect estimates, and new primary studies have been recently published. We aimed to determine whether MPS improves motor recovery and is associated with increased risks for adverse events. We searched MEDLINE, EMBASE, and The Cochrane Library, and two reviewers independently screened articles, extracted data, and evaluated risk of bias. We pooled outcomes from randomized, controlled trials (RCTs) and controlled observational studies separately and used the Grades of Recommendation, Assessment, Development, and Evaluation approach to evaluate confidence. We included four RCTs and 17 observational studies. MPS was not associated with an increase in long-term motor score recovery (two RCTs: 335 participants; mean difference [MD], -1.11; 95% confidence interval [CI], -4.75 to 2.53; p = 0.55, low confidence; two observational studies: 528 participants; MD, 1.37; 95% CI, -3.08 to 5.83; p = 0.55, very low confidence) or improvement by at least one motor grade (three observational studies: 383 participants; risk ratio [RR], 0.84; 95% CI, 0.53-1.33; p = 0.46, very low confidence). Evidence from two RCTs demonstrated superior short-term motor score improvement if MPS was administered within 8 h of injury (two RCTs: 250 participants; MD, 4.46; 95% CI, 0.97-7.94; p = 0.01, low confidence), but risk of bias and imprecision limit confidence in these findings. Observational studies demonstrated a significantly increased risk for gastrointestinal bleeding (nine studies: 2857 participants; RR, 2.18; 95% CI, 1.13-4.19; p = 0.02, very low confidence), but RCTs did not. Pooled evidence does not demonstrate a significant long-term benefit for MPS in patients with acute TSCIs and suggests it may be associated with increased gastrointestinal bleeding. These findings support current guidelines against routine use, but strong recommendations are not warranted because confidence in the effect estimates is limited.
Topics: Acute Disease; Anti-Inflammatory Agents; Hemorrhage; Humans; Methylprednisolone; Randomized Controlled Trials as Topic; Recovery of Function; Spinal Cord Injuries; Treatment Outcome
PubMed: 26529320
DOI: 10.1089/neu.2015.4192