Many physicians have also expressed concern about the use of immunomodulating agents in patients who have been diagnosed with COVID-19, and have said that such interventions could impair the natural immune response to the virus and even increase the risk of secondary bacterial infections.2
“You don’t want to administer this too early or to the wrong patient; you expose someone to undue risk or you might squander the medication that another patient needs. When you look at the spectrum of those patients that have this particular viral infection — you have patients ranging from asymptomatic to critically ill — we are only likely to be giving this to patients who are critically ill,” said Dr Alvarnas.
IL-6 blockade via tocilizumab is not the only immunomodulatory agent being trialled for the treatment of CRS in COVID-19 patients. At press time, there were at least 40 trials looking specifically at tocilizumab and COVID-19. Other avenues of investigation are also focused on IL-1 blockade and the use of corticosteroids.
“As with IL-1 blockers and corticosteroids, people are trying to intervene before the patient gets too sick. I think the timing will be really critical — the patients in respiratory distress, sick enough to be hospitalized, [or who have] a fever and lab features indicating a cytokine storm — this is where you get the best bang for your buck. We know this with IL-1 blockade and it’s likely the same for tocilizumab,” said Dr Cron.
Several companies are running trials of their therapies for COVID-19–associated CRS. Tocilizumab (marketed in the US as Actemra®) is being assessed in a randomized trial (ClinicalTrials.gov Identifier: NCT04320615) by parent company Genentech (and listed as sponsor Hoffmann-La Roche). The company will also examine the drug’s efficacy in an open-label, single-arm phase 2 trial for patients with moderate to severe disease (MARIPOSA; ClinicalTrials.gov Identifier: NCT04363736), and in a randomized, double-blind, placebo-controlled phase 3 trial in patients who have been hospitalized for COVID-19 (ClinicalTrials.gov Identifier: NCT04372186).
“We started hearing anecdotal reports coming out of China at the end of February or early March, where we heard about physicians treating COVID-19 patients with pneumonia with Actemra off-label, with the hypotheses that cytokine release syndrome was happening and could be based on IL-6,” said Mark Eisner, MD, MPH, senior vice president and global head of product development for immunology, infectious diseases and ophthalmology at Genentech.
The trial is running in several countries including the US, Canada, and Europe, with more than 55 sites and 300 patients enrolled, and Dr Eisner confirmed that other than for the treatment of CAR-T–related CRS, Genentech hasn’t previously tested Actemra on cytokine release syndromes caused by any other viral infections or other noninfectious diseases.
“We saw a 21-patient case series from China where they seemed to be seeing some good responses. We knew this was uncontrolled data and wanted to ask the question about Actemra tamping down the immune response, so decided to do the randomized, placebo-controlled trial,” said Dr Eisner, adding that trial enrollment has been brisk and that they hope to release results by early summer.