Patients with moderate to severe pneumonia associated with COVID-19 and high C-reative protein levels may benefit from treatment with the monoclonal antibody tocilizumab, a follow-up study found.
Tocilizumab may be appropriate for treating patients with moderate to severe COVID-19, according to a follow-up analysis of a randomized clinical trial.
A research letter, published in JAMA Internal Medicine, highlighted a follow-up of the CORIMUNO-TOCI-1 randomized clinical trial.
The original investigation, published in October, included 130 patients hospitalized with COVID-19-associated pneumonia who required supplemental oxygen but did not require high-flow or mechanical ventilation. Preliminary results of the study found that the interleukin 6 (IL-6) targeting monoclonal antibody tocilizumab may reduce the need for mechanical ventilation or death by Day 14, but found no difference in mortality over 28 days.
The follow-up study extended the observation period to 90 days and evaluated baseline C-reactive protein (CRP) levels in relation to survival.
The study authors reported that death occurred in 7 out of 63 (11%) participants in the tocilizumab group by Day 90 compared with 11 of 67 (18%) in the group that received usual care (adjusted hazard ratio [HR], 0.64; 95% CI, 0.25-1.65).
“Even if the difference is not statistically significant, this RCT confirms with a long-term outcome (90 days) a tendency to a better survival in patients hospitalized with oxygen requirement (WHO class 5) randomized in the tocilizumab group: adjusted hazard ratio,” Xavier Mariette, MD, PhD, head of rheumatology at Bicetre Hospital in France told Contagion®. “This study demonstrates that long-term (Day 90) outcomes are at least as important than shorter outcomes (Day 28).”
“The second message is that, in a post-hoc analysis, it seems that the drug could benefit more to patients with high inflammation,” Mariette added. “The third message is the good tolerance of tocilizumab. In this population of patients hospitalized on oxygen but not in ICU, there was no increased risk of secondary infections.”
The study showed a greater benefit of tocilizumab in patients with CRP levels greater than 15 mg/dL. Among those patients, the percentage who received noninvasive or invasive ventilation or who died was 18% among the tocilizumab group and 57% among those receiving usual care (HR, 0.18; 95% CI, 0.06-0.59).
Day-90 mortality among those with high CRP levels was 9% among those in the tocilizumab group compared with 35% in the usual care group (HR, 0.18; 95% CI, 0.04-0.89).
“Tocilizumab could be considered in patients hospitalized with moderate to severe pneumonia requiring at least 3L/min of oxygen,” Mariette said. “Definitive conclusion will be given by a meta-analysis of all RCT that is currently on-going by WHO.”
The research letter noted that 8 randomized clinical trials of tocilizumab for COVID-19 have reported mixed results, including 2 studies that included a high rate of patients (greater than 80%) who received dexamethasone. The CORIMUNO-TOCI-1 was set up in March 2020, before dexamethasone was commonly used, and only 16% to 18% of participants were taking steroids at the time of randomization.
“The next step is the meta-analysis of all RCT with IL-6 inhibitors that is currently on-going by WHO,” Marietta said. “The next question is to compare Dexamethasone vs Dexamethasone + Tocilizumab. This trial called TOCIDEX is on-going in our CORIMUNO platform.”
A recent study by investigators in Florida found that tocilizumab was associated with improved inflammatory markers and better respiratory and hemodynamic outcomes in COVID-19 patients requiring mechanical ventilation.
Another study by investigators in New York showed mixed results of tocilizumab in COVID-19 patients, showing that it appeared to reduce the likelihood of deterioration in patients with moderate COVID-19 but didn’t improve the overall survival rate for those with severe illness.
Tocilizumab, which is commonly used to treat rheumatoid arthritis, also didn’t improve clinical status or lower mortality in patients with COVID-19 pneumonia in a recent Phase 3 trial involving 438 patients in 9 countries in Europe and North America.