Sarilumab safe, effective in severe COVID-19 with minor lung consolidation
Although sarilumab fared no better than the standard of care regarding clinical improvement and mortality among patients with severe COVID-19, the drug was linked to faster recovery among patients with minor lung consolidation.
“Severe COVID-19 is characterized by significantly elevated plasma level of the proinflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) suggesting that hyperinflammation may represent a primary instigator of SARS-CoV-2 related ARDS as well as a potential rationale therapeutic target,” Emanuel Della-Torre, MD, of San Raffaele Hospital, in Milan, Italy, and colleagues wrote, “In particular, elevated serum IL-6 levels have been associated to poorer outcome in these patients and with a mortality of nearly 20% at 14 days.”
To evaluate the safety and efficacy of IL-6 blockade with sarilumab (Kevzara, Renegeron and Sanofi) among patients with severe COVID-19 and systemic hyperinflammation, Della-Torre and colleagues conducted an open-label, observational study at San Raffaele Hospital from March 14 through April 2, during the coronavirus outbreak in Italy.
Eligibility criteria for sarilumab treatment included confirmed COVID-19, radiologically documented bilateral pneumonia and hyperinflammation, defined by elevated inflammatory markers and serum IL-6 levels. Other patients who met the inclusion criteria, matched for age, sex, comorbidities, inflammatory markers, respiratory characteristics and radiological findings were enrolled into a control group.
A total of 28 patients were included in the sarilumab group, with another 28 in the control group receiving standard of care. Participants in the sarilumab cohort received 400 mg intravenously in addition to standard of care, and then compared with those treated with standard of care alone. Endpoints included clinical improvement, mortality, safety and response predictors at 28 days.
According to the researchers, 61% of patients treated with sarilumab had experienced clinical improvement at day 28, while 7% died. However, these findings were not significantly different from the control group, in which 64% experienced clinical improvement 64% and 18% died.
Meanwhile, a baseline PaO2/FiO2 ratio greater and 100mm Hg, and a lung consolidation of less than 17% at CT scan, predicted clinical improvement in patients treated with sarilumab. The median time to clinical improvement in patients with lung consolidation less than 17% was 10 days after sarilumab, compared with 24 days following standard treatment (P = .01). The rate of infection and pulmonary thrombosis was similar between groups.
“IL-6 blockade with sarilumab was generally safe and associated with a low mortality rate, which however did not reach statistical significance when compared with what observed in a concomitant group of patients treated with standard of care alone,” Della-Torre and colleagues wrote. “Similarly, sarilumab treatment was not associated to statistically significant improvements in the MV-free survival and in the duration of hospitalization.”
Still, the researchers noted they were comforted by some of their findings, notably that the time to clinical improvement was “significantly shorter” following treatment with sarilumab among patients with minor consolidated lung.
“This last observation suggests that IL-6 blockade might be more effective if administered at a determinate radiological stage of COVID-19 pneumonia, possibly corresponding to an early phase of lung damage,” they wrote. “Finally, our experience advocates considering the use of CT scan for early stratification of hospitalized patients and for enrolment in clinical trials, since the quantification of lung consolidation was among the strongest predictors of clinical progression and response to sarilumab treatment.”