Tocilizumab Augmented Efficacy in COVID-19 Pneumonia with High CRP Save

JAMA Internal Medicine report an analysis of recent and composite trial data suggesting that tocilizumab (TCZ) therapy in COVID-19–associated pneumonia patients with high CRP levels is likely to be effective.

Overall there are 8 clinical trials of tocilizumab treatment in with COVID-19 patients, yielding mixed results. While 4 (66%) achieved their primary end point, improved 28-day survival was only seen in the 2 largest studies, RECOVERY1 and REMAP-CAP.  Both of these trials had a high number of patients taking dexamethasone (>80% of the patients in both treatment arms).  Thus the disparate outcomes in TCZ trials may relate to trial design, patient inclusion, cotherapies and length of follow-up.

The authors previously reported on a trial of tocilizumab in hospitalized COVID patients, showing a reduction in the need for required noninvasive ventilation or intubation, but no difference in survival at day 28. The current report is an extended, 90 day, outcomes report of the CORIMUNO-19 study. A total of 131 O2 requiring, COVID-19 patients were randomized  to either TCZ (64 patients) or usual care group (67 patients).

While there were no differences in survival at day 29, by day 90, deaths were less frequent int he TCZ grou (11% vs 18% in UC; adjusted hazard ratio [HR], 0.64; 95% CI, 0.25-1.65)

When patients were subdivided according to their baseline CRP levels, we found differences at day 14 (primary composite endpoint) and survival at day 90 favoring TCZ patietns with CRP levels greater than 15.0 mg/dL. 

In patients with CRP levels greater than 15.0 mg/dL, primary end point (noninvasive or invasive ventilation or those who died) was met by 18% with TCZ and 57% with UC (HR, 0.18; 95% CI, 0.06-0.59) (Table). Similarly, mortality at day-90 also favored those treated with TCZ (9% vs 35%). 

The study was limited by its small sample size. 

The authors favor tocilizumab in the treatment of patients with moderate-to-severe COVID-19–associated pneumonia and high CRP levels and suggest it should be used in combination with dexamethasone.