CRP Level May Help Guide Use of Tocilizumab in COVID Pneumonia

By Reuters Staff

May 25, 2021

NEW YORK (Reuters Health) - It's worth considering tocilizumab (TCZ) in patients with moderate-to-severe COVID-19-associated pneumonia and high C-reactive protein (CRP) levels, according to follow-up data from a randomized controlled trial.

Several clinical trials have evaluated TCZ for COVID-19 with mixed results.

The French CORIMUNO-TOCI-1 randomized clinical trial enrolled 130 patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive-care unit; 63 received TCZ (8 mg/kg intravenously plus usual care on day 1 and on day 3 if clinically indicated) and 67 received receive usual care alone.

The study, published last year in JAMA Internal Medicine (, met its primary composite endpoint, with fewer patients receiving TCZ needing noninvasive ventilation or intubation or dying at day 14. However, there was no difference in survival at 28 days.

This week in JAMA Internal Medicine, Dr. Xavier Mariette of Bicetre Hospital, in Le Kremlin-Bicetre, and colleagues report extended follow-up to 90 days and looking at whether survival varied with baseline CRP levels.

By day 90, there were non-significantly fewer deaths in the TCZ group (7/63, 11%) than the usual-care group (11/67, 18%), yielding an adjusted hazard ratio of 0.64 (95% confidence interval: 0.25 to 1.65), the researchers report.

They found a statistical interaction between baseline CRP level and the primary composite endpoint at day 14 (need for noninvasive or invasive ventilation or death) and survival at day 90, with a benefit of TCZ in patients with CRP levels above 15.0 mg/dL but not in those with CRP levels at or below 15.0 mg/dL.

Among patients with CRP levels greater than 15.0 mg/dL, four of 22 (18%) treated with TCZ met the primary endpoint compared with 13 of 23 (57%) patients who did not receive TCZ (aHR, 0.18; 95% CI, 0.06 to 0.59).

Likewise, there were fewer deaths at 90 days in the TCZ than the usual group when the baseline CRP level was above 15.0 mg/dL (9% vs 35%, aHR, 0.18; 95% CI: 0.04 to 0.89).

There were no between-group differences in the primary outcome or 90-day mortality when the CRP level was at or below 15.0 mg/dL.

By way of limitations, the researchers caution that "usual care could differ among centers and over time, and few patients were taking steroids at randomization (16% and 18% in the tocilizumab and usual care arms, respectively). The sample size was small and credibility intervals were wide."

They also note that the trial targeted a "narrow segment of the COVID-19 patient population (patients with a World Health Organization Cognitive Performance Scale score of 5 exactly and requiring at least 3 L/min of oxygen), and our results are not generalizable to other populations."

SOURCE: JAMA Internal Medicine, online May 24, 2021.