98 Chapter 5 Outcome measures The primary outcome measure was survival time. Secondary outcome measures were survival time in the Intensive Care Unit (ICU) admitted subpopulation, reaching a combined outcome of ICU admission or mortality, and duration of ICU and hospital admission. Data Data were retrieved by LOGEX (LOGEX BV, Amsterdam, the Netherlands), a Dutch healthcare data company, in collaboration with LCG (National Medicines Coordination Centre). Administrative healthcare data, containing information on a set of baseline characteristics, diagnosis, treatment and other care activities are routinely submitted to LOGEX and these data were re-used for the present analysis. For this study, pseudonymized data from patients with a diagnosis of COVID-19 who were hospitalized between March 2021 up to and including December 2021 were collected. Data from 49 out of 71 Dutch hospitals were available and subsequently included. Details on the calculation of hospital- and ICU LOS can be found in the supplementary information. The datasets analyzed are not publicly available. Summary variables A modified Charlson Comorbidity Index (CCI) was used to summarize comorbidities13. Only the comorbidities were included that were registered in the hospital for which a patient was admitted for COVID-19 and that were registered in the past three years. Therefore, the CCI serves as a proxy parameter for the comorbidity of patients in this study. With the available data the immune status was determined as follows. A patient was considered to be immunocompromised if any of the following conditions were met: organ transplant, bone marrow or stem cell transplantation (autologous or allogeneic), recent (<6 months) treatment for malignant hematological disease, including chemotherapy and CAR-T-cell therapy; cancer therapy for all solid tumors in the last 3 months, including chemotherapy and immune checkpoint inhibitors, and patients treated with immunosuppressive drugs, including B-cell depleting drugs or lymphopenia-inducing medication. No data on chronic corticosteroid use (prior to hospitalization) were available. Allocation of treatment The treatment groups were formed based on the guideline recommendations that were applicable at the time, see Figure 1. The first regimen, from March 15th, 2021 - May 31st, 2021 was 8 mg/kg tocilizumab, max 800 mg (group called “8 mg/kg”). The second regimen, from June 2021- November 2021, was weight-based dosing5, or a fixed dose of 600 mg. Weight-based dosing in the second regimen consisted of 4 groups: 800 mg tocilizumab if weight was >90kg, 600 mg tocilizumab if weight was >65 and ≤90 kg, 400 mg tocilizumab if weight was >40 and ≤65 kg and 8 mg/ kg tocilizumab if weight was <40 kg (group called “Fixed dose tocilizumab”). The third
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