Tocilizumab May Benefit Certain Severe COVID-19 Patients

Patients with moderate to severe cases of COVID-19-associated pneumonia and higher levels of C-reactive protein (CRP) may benefit most from tocilizumab (Actemra), a post-hoc analysis of a French study suggested.

Among patients with CRP levels above 15 mg/dL in the randomized CORIMUNO-TOCI-1 trial, the percentage who required mechanical ventilation or died was significantly lower in the tocilizumab group compared to the usual care group (18% vs 57%, respectively; HR 0.18, 95% CI 0.06-0.59), reported Xavier Mariette, MD, PhD, and co-authors from Hòpital Bicètre in Le Kremlin Bicètre, France.

Moreover, 90-day mortality rate was significantly lower for the tocilizumab group compared to the usual care group, at 9% versus 35% (HR 0.18, 95% CI 0.04-0.89), the authors wrote in a research letter in JAMA Internal Medicine.

The interleukin-6 (IL-6) inhibitor tocilizumab has been associated with decreasing inflammation and is commonly used to treat patients with rheumatoid arthritis. In February, the U.K.’s pragmatic RECOVERY trial reported a slight, but statistically significant mortality benefit in critically ill COVID-19 patients treated with the drug. Also in February, data from the adaptive trial, REMAP-CAP, also found improved survival for patients randomized to the drug.

However, the authors noted these two studies were the only two out of eight randomized trials to find improved 28-day survival with the drug. These trials had other potential confounders, such as RECOVERY only enrolling patients with elevated CRP levels and 80% of patients in REMAP-CAP using dexamethasone.

For the primary analysis of CORIMUNO-TOCI-1 — a composite endpoint of progression to non-invasive or invasive mechanical ventilation or death at day 14, with a 28-day survival follow-up — Xavier and colleagues’ previously reported no improvement with tocilizumab among hospitalized patients receiving oxygen, but not high-flow oxygen or mechanical ventilation.

The current study provided an extended follow-up time of 90 days. Xavier’s group also assessed survival variance with baseline CRP levels.

Overall, 63 patients received tocilizumab, while 67 received usual care. By 90 days, 11% of patients died in the tocilizumab group and 18% of patients died in the usual care group (HR 0.64, 95% CI 0.25-1.65). However, when outcomes were analyzed by CRP levels, there was a “statistical interaction” between the primary composite endpoint at day 14 and survival at day 90.

The new analysis demonstrates that longer-term outcomes “are at least as important” as shorter-term outcomes, Mariette told MedPage Today by email, adding that the post-hoc analysis suggests the drug could be of more benefit to patients with high levels of inflammation.

Tocilizumab benefitted patients with CRP levels above 15.0 mg/dL, but not CRP levels at or below 15.0 mg/dL.

“Tocilizumab could be considered in patients hospitalized with moderate to severe pneumonia requiring at least 3 L/min of oxygen,” Mariette said. “Definitive conclusion will be given by a meta-analysis of all [randomized trials] that is currently on-going by [the World Health Organization].”

CORIMUNO-TOCI-1 was started in March 2020, when very few patients were taking steroids (16% in the tocilizumab group and 18% in the usual care group), Mariette told MedPage Today. “That has become the standard of care for these patients with moderate to severe pneumonia.”

The next question will be to compare dexamethasone with or without tocilizumab in the TOCIDEX trial, he said.

Other limitations of the study included its small sample size and that usual care practices can vary in different medical centers as well as with time. This study also only covered a very limited, highly specific population, so the data cannot be generalized to broader groups.