Tocilizumab Therapy Tied to Better Outcomes of Severe COVID-19

By Will Boggs MD

July 07, 2020

NEW YORK (Reuters Health) - Tocilizumab therapy is associated with a lower risk of invasive mechanical ventilation or death in patients with severe COVID-19, according to a new study.

Tocilizumab is a recombinant humanized monoclonal antibody directed against the soluble and membrane-bound forms of the interleukin-6 (IL-6) receptor. One small study in China and anecdotal observations have suggested the drug can provide a clinical benefit in patients with COVID-19 at risk for cytokine storm.

Dr. Christina Mussini of the University of Medina and Reggio Emilia, in Modena, Italy, and colleagues used medical records from three tertiary-care centers in Italy to assess the role of tocilizumab in reducing the risk of invasive mechanical ventilation or death in patients with severe COVID-19 pneumonia who also received standard of care treatment.

The study included 91 patients treated with subcutaneous tocilizumab (two simultaneous doses of 162 mg each, one in each thigh), 88 patients treated with intravenous tocilizumab (8 mg/kg bodyweight up to a maximum of 800 mg administered twice, 12 hours apart), and 365 controls treated according to regional standard of care.

After baseline, more patients treated with tocilizumab (30%) than with standard of care alone (17%) also started glucocorticoids.

Invasive mechanical ventilation was started in similar fractions of both groups (18% of tocilizumab patients vs. 16% of standard-care patients). But significantly fewer patients in the tocilizumab group (7%) than in the standard-care group (20%) died, the researchers report in The Lancet Rheumatology.

At day 14 after hospital admission, the proportion of patients with the composite primary outcome of invasive mechanical ventilation or death was significantly lower in the tocilizumab group (22.6%) than in the standard-care group (36.5%). This apparent benefit was similar for both the intravenous and subcutaneous tocilizumab groups.

After controlling for sex, age, SOFA score, and duration of symptoms, tocilizumab was associated with a 39% reduction in the risk of invasive mechanical ventilation or death, compared with receiving standard of care only (P=0.02).

Adverse events remain a concern. More patients treated with tocilizumab than with standard of care were diagnosed with new infections (13% vs. 4%; P<0.0001).

"Tocilizumab use in severe COVID-19 pneumonia is still in its infancy, and the best treatment strategies have yet to be developed," the authors conclude. "Although these results are encouraging, they should be confirmed in ongoing randomized studies."

Dr. Grant S. Schulert of Cincinnati Children's Hospital Medical Center and the University of Cincinnati College of Medicine, in Ohio, who wrote an accompanying editorial, told Reuters Health by email, "Tocilizumab appears to provide benefit when given to severely ill patients before they progress to full-on respiratory failure. We don't yet know if this is a better choice than something like IL-1 blockade or even corticosteroids, and particularly if there are patient-specific biomarkers or side-effect profiles that would help guide that decision."

"The concern with cohort studies such as this is always whether cases and controls are really comparable," he said. "Here, indeed, there are clear differences in patients who received tocilizumab - they were younger, sicker, and had more comorbidities. However, I found it very encouraging that this study found reduced mortality in COVID-19 patients treated with tocilizumab even when adjusting for age and baseline severity of respiratory disease."

"As I noted in my editorial," Dr. Schulert added, "this study is a particularly commendable effort for being performed at the height of the outbreak in Northern Italy when the healthcare infrastructure was near collapse. Despite these unprecedented challenges, the authors were able to trial this therapy in a pre-specified and consistent manner."

Dr. Jared Radbel of Rutgers-Robert Wood Johnson Medical School, in New Brunswick, New Jersey, who recently reported the use of tocilizumab for COVID-19-induced cytokine release syndrome in two patients, told Reuters Health by email, "Tocilizumab should be considered for use in severely ill patients who display signs of excessive inflammation."

"There is a suggestion that tocilizumab may improve mortality in patients with severe pneumonia due to COVID-19," he said. "However, one must recognize this is a retrospective study with uncontrolled factors creating heterogeneity in each treatment group."

"The 'standard of care' group is no longer what I would consider standard of care in the U.S.," added Dr. Radbel, who was not involved in the study. "In addition, the follow-up period was relatively short (14 days); this may not have been long enough to see adverse outcomes from the increased risk of superimposed infections."

"We must wait for data from randomized controlled trials before making a conclusion on the use of tocilizumab in COVID-19," he concluded.

Dr. Mussini did not respond to a request for comments.

SOURCE: https://bit.ly/2Bno7ph and https://bit.ly/2ZuKvVz Lancet Rheumatology, online June 24, 2020.

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