Tocilizumab prescribing criteria for COVID-19 patients

KEYWORDS:

• Tocilizumab
• COVID-19
• SARS-CoV-2
• interleukin 6
• cytokine storm
• monoclonal antibody

Dear Editor,

COVID-19, a pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected over 25 million confirmed patients with almost 1 million fatalities (3.4%) (https://coronavirus.jhu.edu/map.html). Numerous reports have discussed the role of cytokine storm in the disease pathogenesis and prognosis, with Interleukin-6 (IL-6) as the apparent primary contributor to this storm.^1–3 Subsequently, Tocilizumab (Actemra®), as a humanized monoclonal antibody, showed promising results in decreasing the inflammatory responses and improving patient’s conditions in many retrospective clinical trials, which were limited to small sample sizes.^4–7 The primary laboratory indicator that determines the proper time to start Tocilizumab treatment should be the blood IL-6 level, which unfortunately is unavailable in all countries or treatment centers. Accordingly, many hospitals have adopted different criteria to decide on the appropriate patients for Tocilizumab and the optimal time for its initiation. Eligibility may rely on meeting five different criteria: worsening gas exchange and levels of D-Dimer, C-reactive protein, 111ferritin and Lactate Dehydrogenase. A more flexible approach is for patients to meet 1–4 of these five criteria to be considered a candidate for therapy initiation.

A retrospective observational study (registered and approved by Johns Hopkins Aramco Healthcare IRB committee under IRB# 20–13, 6/23/2020) analyzed the data of 90 COVID-19 patients (blood oxygen saturation, WBC, CRP, ferritin, D-Dimer, Alkaline phosphatase, ALT, AST, LDH, ICU length of stay after Tocilizumab administration, total ICU length of stay, total hospital length of stay, and mortality) admitted to the ICU units at Johns Hopkins Aramco Healthcare. Analysis of Tocilizumab infusion revealed that relying in one parameter to decide the initiation of treatment is not enough and that at least two inflammatory parameters need to be met concurrently (ferritin ≥1000 ng/mL and blood CRP ≥10 mg/dL) for drug prescribing and administration while excluding the role of D-Dimer blood level as an indicator for drug administration. While the administration time is another area of debate, our data revealed that these two parameters should be measured on a daily basis, and the time at which the patient meets these two criteria is the optimal time to initiate drug treatment. Regarding the proper dosing level, no significant differences have been observed in different laboratory biomarkers (CRP, ferritin, WBC, ALT, AST, LDH) between patients receiving a fixed standard dose of Tocilizumab (400 mg or 800 mg IV) and patients receiving a weight-based dose (8 mg/mL IV), which indicates that the Tocilizumab dose can be rounded to the available vial size (80, 200 or 800 mg).

These data are part of two ongoing studies at JHAH, I. Prescribing patterns and clinical effectiveness of Tocilizumab in COVID-19 patients, and II. Tocilizumab as an optimal option for COVID-19 patients, when to start? As a Systematic review and Meta-analysis.