Long-term functional prognosis with tocilizumab in severe COVID-19 infection: A multicenter prospective observational study on mechanically ventilated ICU patients in the COVID-19 recovery study II

Article

作者: Hatakeyama, Junji ; Ota, Kohei ; Oshima, Taku ; Muto, Yoko ; Kawauchi, Akira ; Iba, Arisa ; Hori, Miyuki ; Kanda, Naoki ; Nakamura, Kensuke ; Fujitani, Shigeki ; Kamijo, Hiroshi ; Hosozawa, Mariko ; Asahi, Tomohiro ; Iso, Hiroyasu ; Kato, Hideaki

BACKGROUNDTocilizumab, an IL-6 receptor antagonist, may prevent functional impairments in critically ill patients by attenuating the cytokine storm. This study investigated a potential effect of tocilizumab on preventing functional impairments in patients with severe coronavirus infection 2019 (COVID-19).METHODSIn a multicenter prospective observational study, patients with COVID-19 ≥ 20 years requiring mechanical ventilation admitted to the intensive care unit between April 2021 and September 2021 and discharged alive were followed for one year. A self-administered questionnaire on sequelae and functional impairments was mailed in August 2022, and data were collected. A multivariate logistic regression was used to assess the impact of tocilizumab on physical function, mental health, and Long COVID.RESULTSOf 157 analyzed patients, 41 received tocilizumab. The tocilizumab group had more severe illness, but a lower prevalence of physical impairment (17.1 % vs. 23.3 %, p = 0.41) and mental disorders (19.5 % vs. 39.7 %, p = 0.009) than the non-tocilizumab group. The prevalence of Long COVID was higher in the tocilizumab group (92.7 % vs. 80.2 %, p = 0.06), whereas fatigue/malaise was significantly lower (19.5 % vs. 37.1 %, p = 0.039). Adjusted odds ratios (95 % confidence interval) for physical impairment, mental disorders, and Long COVID with tocilizumab were 0.70 (0.2-2.1), 0.40 (0.16-1.01), and 2.94 (0.7-12.3), respectively, with no significant difference.CONCLUSIONSTocilizumab was associated with a lower prevalence of physical impairment and mental disorders at 1 year in patients with severe COVID-19. Furthermore, Long COVID had a weaker impact on physical and cognitive functions.

2025-04-01·Journal of Intensive Care Medicine

Outcomes Associated with the use of High Dose Corticosteroids and IL-6 Inhibitors for the Treatment of Acute Respiratory Distress Syndrome Secondary to SARS COV-2

Article

作者: Milic, Tessa ; Shah, Kieran ; Stabler, Sarah ; Mitra, Anish

BackgroundDuring the COVID-19 pandemic, treatment strategies evolved rapidly. The RECOVERY trial established corticosteroids as the standard care for reducing mortality in COVID-19 patients. However, some critical care clinicians began using doses higher than those recommended in RECOVERY.ObjectiveTo characterize the use of high-dose corticosteroids and IL-6 inhibitors in critically ill COVID-19 patients and examine their association with adverse drug events (ADEs).MethodsA retrospective cohort study of 320 electronic health records (January 1, 2020 - June 30, 2022) was conducted on COVID-19 patients requiring high-flow oxygen or mechanical ventilation. Patients were categorized based on corticosteroid dose: “high dose dexamethasone” (daily dose greater than 12 mg and/or for longer than 10 days), “low dose dexamethasone” (daily dose 12 mg or less for 10 days or less), and “no dexamethasone” (no corticosteroid therapy). Subgroups were created based on IL-6 inhibitor use.ResultsHigh-dose dexamethasone was associated with increased odds of ADEs compared to low dose (OR 2.55, 95% CI 1.45 to 4.49) and no dexamethasone (OR 6.29, 95% CI 2.08 to 19.03). No additional efficacy benefit was observed in patients receiving high dose corticosteroids when compared to low dose corticosteroids. Patients receiving both an IL-6 inhibitor and high-dose dexamethasone had further increased odds of ADEs. High-dose dexamethasone was also associated with increased mortality compared to low dose (OR 3.78, 95% CI 1.97-7.25) and no dexamethasone (OR 15.22, 95% CI 3.27-70.74).ConclusionsAcknowledging the risk for residual confounding, higher doses of dexamethasone were associated with increased ADEs and mortality. These findings highlight the need for careful consideration of the use of high-dose dexamethasone.

2025-03-01·Rheumatology

Tocilizumab discontinuation after remission achievement in patients with adult-onset Still’s disease

Article

作者: Takeuchi, Tsutomu ; Kondo, Yasushi ; Kaneko, Yuko ; Tamai, Hiroya

AbstractObjectivesTocilizumab, an IL-6 inhibitor, has been proven effective in patients with adult-onset Still's disease (AOSD). This study aimed to clarify whether tocilizumab can be discontinued after achieving remission and to identify factors relevant to its successful discontinuation.MethodsConsecutive patients with AOSD diagnosed according to Yamaguchi's criteria from April 2012 to July 2022, who were treated with tocilizumab, were retrospectively reviewed.ResultsForty-eight patients with AOSD treated with intravenous tocilizumab, with sufficient information, were included. Thirty-eight patients (79.2%) achieved remission after 6 months of tocilizumab treatment, 12 of whom discontinued tocilizumab during remission. Within 1 year after tocilizumab discontinuation, six patients (50.0%) recurred at a mean of 5.5 months, while the other six (50.0%) remained in remission. Between the non-recurrence and recurrence groups, no difference was found in disease activity at tocilizumab discontinuation (systemic feature score, P = 0.24; ferritin, P = 0.46). While the duration of tocilizumab use was not different (P = 0.32), the interval of tocilizumab administration at tocilizumab discontinuation in the recurrence group was 21 (14–35) days, which tended to be shorter than 35 (28–53) days in the non-recurrence group (P = 0.08). Patients with prednisolone dose <7 mg/day at last tocilizumab treatment had fewer recurrences than those without (P = 0.001). After recurrence, tocilizumab was resumed in half of the patients, resulting in successful disease control.ConclusionsThe recurrence rate after tocilizumab discontinuation was 50% in 1 year. Patients who remained in remission with a longer interval of tocilizumab administration and lower prednisolone dose were likely to succeed in the withdrawal of tocilizumab.

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