tocilizumab in covid19

Tocilizumab in hospitalized patients with COVID-19

tocilizumab in covid 19 trial

Tocilizumab is an antiinflammatory monoclonal antibody that was initially developed for rheumatoid arthritis. Based on its antiinflammatory mecahnism of action, it was hypothesized to have efficacy against COVID-19 infection. This was specifically seen in a retrospective study that was published in The Lancet where tocilizumab showed to reduce the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia.

Clinical Question of the BACC bay Tocilizumab trial:

To evaluate whether early intervention with interleukin-6 receptor blockade (tocilizumab) limits the progression of COVID-19 pneumonia patients to hypoxemic respiratory failure or death, reduces the risk of clinical worsening, and decrease the duration of supplemental oxygen use.

Bottom Line:

Tocilizumab was not effective for preventing intubation or death in moderately ill hospitalized patients with Covid-19.

Trial Design:

Randomized, investigator-initiated, placebo-controlled trial

Population:

N= 243 patients; N=161(tocilizumab), N=82 (placebo)
141 (58%) were men, and 102 (42%) were women.
Median age was 59.8 years

Inclusion Criteria:

  • Patients 19 to 85 years of age
  • SARS-CoV-2 infection confirmed by either nasopharyngeal swab polymerase chain reaction or serum IgM antibody assay.
  • Patients had to have at least two of the following signs: fever (body temperature >38°C) within 72 hours before enrollment, pulmonary infiltrates, or a need for supplemental oxygen in order to maintain an oxygen saturation higher than 92%.
  • At least one of the following laboratory criteria also had to be fulfilled: a C-reactive protein > 50 mg/l, a ferritin level> 500 ng/ml, a d-dimer level higher than 1000 ng/ml, or an LDH level > 250 U/L.

Exclusion Criteria:

  • Patients were excluded if they were receiving supplemental oxygen at a rate that exceeded 10 L/m, if they had a recent history of treatment with biologic agents or small-molecule immunosuppressive therapy, if they were receiving other immunosuppressive therapy that the investigator believed placed them at higher risk for an infection, or if they had had diverticulitis.

Primary Outcomes:

  1. Mechanical ventilation or death %

At day 28, 17 patients (10.6%) in the tocilizumab group and 10 patients (12.5%) in the placebo group had been intubated or had died . No difference was noted P=0.64

Key Secondary Outcomes:

1. Clinical worsening on ordinal scale

Again, no difference was noted between groups. P=0.73

2. Discontinuation of supplemental O2

At 28 days, 82.6% patients in tocilizumab group were off of O2 compared to 84.9% in placebo group.

Take Home Point:

IL6 inhibitor tocilizumab did not show any benefits when it comes to the treatment of inpatient COVID-19 patients. Some patients received remdesivir as concomitant treatment, whereas no patients received dexamethasone. Despite that, no difference was noted in the final outcomes. This is in contrast to the findings of ACTT-1 and RECOVERY trial that showed benefit of dexamethasone and Remedesivir in COVID-19 pneumonia, respectively.

Source: NEJM