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14-07-2020 | COVID-19 | News

IL-6 inhibitors show potential for COVID-19

Author: Claire Barnard


medwireNews: Add-on treatment with an interleukin (IL)-6 receptor inhibitor warrants further investigation for patients with severe COVID-19 pneumonia and systemic hyperinflammation, suggest preliminary findings from two Italian observational studies published in the Annals of the Rheumatic Diseases.

In the first, the researchers evaluated the outcomes of 40 patients from Pescara General Hospital who were treated with subcutaneous tocilizumab 324 mg (given as two injections) in addition to local standard of care (SOC), compared with 40 age- and sex-matched patients treated with SOC only. SOC in the two groups included hydroxychloroquine in 88–98% of patients, darunavir/cobicistat in 33–53%, lopinavir/ritonavir in 5%, and corticosteroids in 58–65%.

Giustino Parruti (Pescara General Hospital) and colleagues found that patients given tocilizumab had a significantly lower risk for disease progression (requirement for invasive mechanical ventilation or death) compared with those in the SOC only group, at rates of 5% versus 30%, and mortality, at 5% versus 28%.

Treatment with tocilizumab also resulted in an improvement of oxygenation and a reduction in C-reactive protein (CRP) levels, whereas both variables worsened in the control group.

Parruti et al say that the IL-6 inhibitor was “well tolerated, with no serious or clinically relevant adverse events.”

They conclude: “While limited by the small number of patients included and the non-random nature of the comparisons, data appear reassuring in terms of safety, and encouraging when compared with those of patients treated with SOC in our centre or other published cohorts.”

The second study, by Emanuel Della-Torre and colleagues from San Raffaele Hospital in Milan, Italy, involved 28 patients given a single intravenous infusion of sarilumab 400 mg in addition to local SOC (lopinavir/ritonavir, hydroxychloroquine, and azithromycin) and 28 treated with SOC alone.

During 28 days of follow-up, rates of clinical improvement (discharge from hospital and/or a decrease of 2 points or more from baseline on the six-category ordinal scale) were comparable among patients in the sarilumab group compared with the SOC group, at 60% and 64%, respectively. Mortality rates were numerically lower in the sarilumab group, at 7% versus 18% for those given SOC, but the difference did not reach statistical significance.

However, sarilumab-treated patients had a significantly longer median time to death than those given SOC (19 vs 4 days), as well as a significantly shorter median time to fever resolution (1 vs 4 days) and CRP normalization (6 vs 12 days).

On multivariate analysis, the partial pressure of arterial oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, percentage of lung consolidation, and total volume of consolidated lung were identified as significant predictors of clinical improvement.

And using receiver operating characteristic curve analysis, the researchers demonstrated that having a proportion of lung consolidation below 17% on a computed tomography scan predicted clinical improvement after sarilumab treatment with 100% sensitivity and 75% specificity.

These findings suggest “that quantification of lung consolidation should be considered when treating patients with COVID-19 with IL-6 blocking agents as well as when designing clinical trials with alternative experimental drugs,” write Della-Torre and team.

Conversely, they note that “baseline serum IL-6 level was […] not associated with clinical improvement or overall survival” in their study, “a finding that contrasts with the accepted notion of IL-6 being a predictor of dismal prognosis in patients with COVID-19.”

The team says that sarilumab had a favorable safety profile in their study, with adverse events reported in 43% and 36% of patients in the sarilumab and control groups, respectively, and a corresponding 21% and 18% experiencing bacterial infections.

medwireNews is an independent medical news service provided by Springer Healthcare. © 2020 Springer Healthcare part of the Springer Nature Group

14 July 2020: The coronavirus pandemic is affecting all healthcare professionals across the globe. Medicine Matters’ focus, in this difficult time, is the dissemination of the latest data to support you in your research and clinical practice, based on the scientific literature. We will update the information we provide on the site, as the data are published. However, please refer to your own professional and governmental guidelines for the latest guidance in your own country.

Ann Rheum Dis 2020; doi: 10.1136/annrheumdis-2020-218243
Ann Rheum Dis 2020; doi:10.1136/annrheumdis-2020-218122