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Report of a combination of remdesivir, intravenous methylprednisolone pulse, and tocilizumab for severe coronavirus disease: 20-case series at a single institution.

ABSTRACT: Many drugs have been marketed for treating coronavirus disease 2019 (COVID-19) infection, the disease that has caused a worldwide pandemic. However, in reported clinical trials, almost 30% of patients with COVID-19 did not show any health improvement. The 28-day survival rate was 69.5% when patients who required highflow oxygen therapy (HFNC), ventilation, and extracorporeal membrane oxygenation (ECMO) management were treated with remdesivir. The mortality rate of patients receiving 6 mg dexamethasone was 27%, and that of patients treated with tocilizumab and steroids was 31%. These results are unsatisfactory, and treatment for patients with severe respiratory failure has not yet been established. In our institution, we used remdesivir, methylprednisolone (mPSL) pulse therapy, and tocilizumab in 20 patients with COVID-19 whose PaO2/FIO2 (P/F) ratio was <200, and obtained good results for this combination therapy without any adverse events. In this study, we report the possible efficacy and safety of this treatment.

SUBMITTER: Ichiyama T

PROVIDER: S-EPMC9035365 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Report of a combination of remdesivir, intravenous methylprednisolone pulse, and tocilizumab for severe coronavirus disease: 20-case series at a single institution.

Ichiyama Takashi T Komatsu Masamichi M Wada Yosuke Y Hanaoka Masayuki M

Respiratory investigation 20220425 4

Many drugs have been marketed for treating coronavirus disease 2019 (COVID-19) infection, the disease that has caused a worldwide pandemic. However, in reported clinical trials, almost 30% of patients with COVID-19 did not show any health improvement. The 28-day survival rate was 69.5% when patients who required highflow oxygen therapy (HFNC), ventilation, and extracorporeal membrane oxygenation (ECMO) management were treated with remdesivir. The mortality rate of patients receiving 6 mg dexamet ...[more]

PMID: 35501265

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Project description:Dysregulated neutrophil and platelet interactions mediate immunothrombosis and cause lung injury in coronavirus disease 2019. IV immunoglobulin modulates neutrophil activation through Fc?RIII binding. We hypothesized that early therapy with IV immunoglobulin would abrogate immunothrombosis and improve oxygenation and reduce progression to mechanical ventilation in coronavirus disease 2019 pneumonia. Design:Prospective randomized open label. Setting:Inpatient hospital. Patients and Intervention:Hypoxic subjects with coronavirus disease 2019 pneumonia were randomized 1:1 to receive standard of care plus IV immunoglobulin 0.5?g/kg/d with methylprednisolone 40?mg 30 minutes before infusion for 3 days versus standard of care alone. Main Results:Sixteen subjects received IV immunoglobulin and 17 standard of care. Median ages were 51 and 58 years for standard of care and IV immunoglobulin, respectively. Acute Physiology and Chronic Health Evaluation II and Charlson comorbidity scores were similar for IV immunoglobulin and standard of care. Seven standard of care versus two IV immunoglobulin subjects required mechanical ventilation (p = 0.12, Fisher exact test). Among subjects with A-a gradient of greater than 200?mm Hg at enrollment, the IV immunoglobulin group showed: 1) a lower rate of progression to requiring mechanical ventilation (2/14 vs 7/12, p = 0.038 Fisher exact test), 2) shorter median hospital length of stay (11 vs 19 d, p = 0.01 Mann Whitney U test), 3) shorter median ICU stay (2.5 vs 12.5 d, p = 0.006 Mann Whitey U test), and 4) greater improvement in Pao2/Fio2 at 7 days (median [range] change from time of enrollment +131 [+35 to +330] vs +44·5 [-115 to +157], p = 0.01, Mann Whitney U test) than standard of care. Pao2/Fio2 improvement at day 7 was significantly less for the standard of care patients who received glucocorticoid therapy than those in the IV immunoglobulin arm (p = 0.0057, Mann Whiney U test). Conclusions:This pilot study showed that IV immunoglobulin significantly improved hypoxia and reduced hospital length of stay and progression to mechanical ventilation in coronavirus disease 2019 patients with A-a gradient greater than 200?mm Hg. A phase 3 multicenter randomized double-blinded clinical trial is under way to validate these findings.

Project description:Abstract BACKGROUND: Adamantinomatous craniopharyngioma (ACP) is a devastating skull-base tumor believed to derive from epithelial remnants of the primordial craniopharyngeal duct (Rathke’s pouch), which gives rise to the anterior pituitary gland. ACP lacks medical antitumor therapies. Current standard therapy with surgery and radiation is associated with poor quality of life. Clinical and preclinical data indicate that IL-6 blockade may contribute to ACP tumor control. METHODS: Children aged 2–21 years with newly diagnosed or previously treated ACP with measurable disease are eligible for the Phase 0/feasibility single-institution clinical trial (NCT03970226) of intravenous (IV) tocilizumab at Children’s Hospital Colorado. The phase I stratum involves IV tocilizumab prior to a standard-of-care surgical resection. The feasibility portion of the trial involves IV tocilizumab every two weeks for up to 13 28-day cycles. Tocilizumab is administered at the established weight-based pediatric dosage of 8 mg/kg for patients who weigh ≥30kg or 12 mg/kg for patients who weigh <30kg. RESULTS: To date, three patients have been enrolled on the Phase 0 component of the trial. These patients demonstrated clinically relevant levels of tocilizumab (≥ 4µg/mL) in serum, cyst fluid, and/or tumor tissue, compared to undetectable levels in control samples. Two patients (1 male and 1 female; median age 10.5 years) have enrolled on the feasibility stratum; one patient had best response of minor response but met definition of progressive disease at cycle 11. One patient with extensive disease required dose reduction for myelosuppression. CONCLUSION: Systemic delivery of tocilizumab at the established pediatric dosage is promising for treatment of ACP based on preclinical work and its demonstrated penetration into cystic and solid portions of ACP tumors. The therapy to date has been well tolerated overall. Further study is planned through a CONNECT consortium international Phase II trial.

Project description:BackgroundSteroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias.MethodsWe performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020-2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy.ResultsDuring the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52-0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02-3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40-250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71-0.89).ConclusionThe results of our study suggest that intravenous methylprednisolone showed dose-response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Dataset Information

Report of a combination of remdesivir, intravenous methylprednisolone pulse, and tocilizumab for severe coronavirus disease: 20-case series at a single institution.

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Report of a combination of remdesivir, intravenous methylprednisolone pulse, and tocilizumab for severe coronavirus disease: 20-case series at a single institution.

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