A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages

Swets, Maaike; Moss, Rob J; Kor, Flip; Hilarius, Doranne L.; Moes, Dirk Jan A R; Berkhout, Willemijn EM; Toorn, Leon M. van den; Oever, Niels C. Gritters van den; Valk, Renee de; Rosendaal, Frits R.; Hunfeld, Nicole; Groeneveld, Geert H.; Boer, Mark GJ de

doi:10.1016/j.ijid.2023.01.041

Cited by 4 publications

(4 citation statements)

References 14 publications

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“…In patients with COVID-19, both tocilizumab and sarilumab improved outcome measures, but tocilizumab showed more promise in reducing mortality at four weeks and progression to the need for mechanical ventilation in patients with moderate-tosevere COVID-19 [70], which is something that a further network meta-analysis [71] and a systematic review and metanalysis [72] could not demonstrate. The two drugs were found to be of similar potency in reducing 60-day mortality in patients with severe COVID-19 with the lower tocilizumab dose (8 mg/kg) showing the best results [73], while in another Bayesian network meta-analysis, both drugs were effective at reducing the mortality of severe and critical COVID-19 patients when used in combination with corticosteroids [74]. We were not able to conduct a balanced comparison between tocilizumab and sarilumab due to the fact that the administration of the latter is subordinated to the unavailability of the former.…”

Section: Discussionmentioning

confidence: 95%

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Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study

Simonetti,

Restaino,

Bernardi

et al. 2024

Brain Sciences

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Interleukin 6 (IL-6) receptor inhibitors tocilizumab and sarilumab have recently been approved for severe coronavirus disease 2019 (COVID-19). They also affect mood, even though their effect on the post-COVID-19 syndrome-related psychopathology still has to be investigated. The aim of this study was to investigate their effect on psychopathology in a sample of patients with post-COVID-19 syndrome. We included 246 patients (34% female, 66% male) aged 18–75 years who had been hospitalized for COVID. Patients were split into those who received anti-IL-6 receptor agents (Anti-IL-6-R, N = 88) and those who did not (Ctrl, N = 158). The former group was further split into those receiving tocilizumab (TOC, N = 67) and those receiving sarilumab (SAR, N = 21). Groups were compared based on clinical characteristics before and during COVID-19 as well as on physical and psychiatric symptoms after COVID-19. Ctrl had less psychiatric and physical symptoms during hospitalization and more post-COVID-19 diarrhea, headache, cough, and dyspnea upon exertion than those receiving IL-6-receptor inhibitors. Ctrl also showed greater difficulties in emotion regulation. These differences were driven by TOC vs. Ctrl, whereas differences between SAR and Ctrl or TOC did not reach significance. IL-6 receptor inhibitors are related to a lower post-COVID-19 illness burden and seem to be effective in emotion regulation. Further research is needed to confirm these findings.

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Section: Discussionmentioning

confidence: 95%

“…We were not able to conduct a balanced comparison between tocilizumab and sarilumab due to the fact that the administration of the latter is subordinated to the unavailability of the former. A shortage of tocilizumab was one reason why patients in the Swets et al [73] study were switched to sarilumab.…”

Section: Discussionmentioning

confidence: 99%

Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study

Simonetti,

Restaino,

Bernardi

et al. 2024

Brain Sciences

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“…From September 2020 patients with COVID-19 were treated with dexamethasone and from January 2021 with dexamethasone and tocilizumab. 10 In patients who deteriorated with an unknown cause, hyperinflammation was suspected and these patients were mostly treated with methylprednisolone.…”

Section: Methodsmentioning

confidence: 99%

Prospective and systematic screening for invasive aspergillosis in the ICU during the COVID-19 pandemic, a proof of principle for future pandemics

van Grootveld,

van Paassen,

Claas

et al. 2024

Medical Mycology

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The diagnostic performance of a prospective, systematic screening strategy for COVID-19 associated pulmonary aspergillosis (CAPA) during the COVID-19 pandemic was investigated. Patients with COVID-19 admitted to the ICU were screened for CAPA twice weekly by collection of tracheal aspirate (TA) for Aspergillus culture and PCR. Subsequently, bronchoalveolar lavage (BAL) sampling was performed in patients with positive screening results and clinical suspicion of infection. Patient data were collected from April 2020–February 2022. Patients were classified according to 2020 ECMM/ISHAM consensus criteria. In total, 126/370 (34%) patients were positive in screening and CAPA frequency was 52/370 (14%) (including 13 patients negative in screening). CAPA was confirmed in 32/43 (74%) screening positive patients who underwent BAL sampling. ICU mortality was 62% in patients with positive screening and confirmed CAPA, and 31% in CAPA cases who were screening negative. The sensitivity, specificity, positive and negative predictive value (PPV & NPV) of screening for CAPA were 0.71, 0.73, 0.27 and 0.95 respectively. The PPV was higher if screening was culture positive compared to PCR positive only, 0.42 and 0.12 respectively. CAPA was confirmed in 74% of screening positive patients, and culture of TA had a better diagnostic performance than PCR. Positive screening along with clinical manifestations appeared to be a good indication for BAL sampling since diagnosis of CAPA was confirmed in most of these patients. Prospective, systematic screening allowed to quickly gain insight into the epidemiology of fungal superinfections during the pandemic and could be applicable for future pandemics.

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“…Early during the pandemic strong inflammation was recognized as hallmark of COVID-19 disease, and specific targeting strategies were sought and examined to minimize inflammation associated damage without affecting viral elimination 2 , 4 , 6 . IL-6 targeting successfully reduced mortality and disease duration in critically-ill patients 6 – 10 , accompanied by long-term beneficial effects 11 . Also the administration of anakinra (a selective IL-1 inhibitor) increased the chance of recovery, in most patients 6 , 12 – 15 .…”

Section: Introductionmentioning

confidence: 99%

Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease

van Meijgaarden,

van Veen,

Tsonaka

et al. 2024

Sci Rep

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SARS-CoV2 infection results in a range of disease severities, but the underlying differential pathogenesis is still not completely understood. At presentation it remains difficult to estimate and predict severity, in particular, identify individuals at greatest risk of progression towards the most severe disease-states. Here we used advanced models with circulating serum analytes as variables in combination with daily assessment of disease severity using the SCODA-score, not only at single time points but also during the course of disease, to correlate analyte levels and disease severity. We identified a remarkably strong pro-inflammatory cytokine/chemokine profile with high levels for sCD163, CCL20, HGF, CHintinase3like1 and Pentraxin3 in serum which correlated with COVID-19 disease severity and overall outcome. Although precise analyte levels differed, resulting biomarker profiles were highly similar at early and late disease stages, and even during convalescence similar biomarkers were elevated and further included CXCL3, CXCL6 and Osteopontin. Taken together, strong pro-inflammatory marker profiles were identified in patients with COVID-19 disease which correlated with overall outcome and disease severity.

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A comparison of the effectiveness of different doses of tocilizumab and sarilumab in the treatment of severe COVID-19: a natural experiment due to drug shortages

Cited by 4 publications

References 14 publications

Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study

Effect of Anti-Interleukin-6 Agents on Psychopathology in a Sample of Patients with Post-COVID-19 Syndrome: An Observational Study

Prospective and systematic screening for invasive aspergillosis in the ICU during the COVID-19 pandemic, a proof of principle for future pandemics

Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage activation and disease severity in COVID-19 disease

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