Hydroxychloroquine and tocilizumab therapy in COVID-19 patients-An observational study

Abstract

Hydroxychloroquine has been touted as a potential COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has also been proposed as a treatment of critically ill patients. In this retrospective observational cohort study drawn from electronic health records we sought to describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Patients were hospitalized at a 13-hospital network spanning New Jersey USA between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials. Trial Registration: Clinicaltrials.gov Identifier: NCT04347993.

Fig 1. Cohort selection flow diagram.

Flow Diagram of patient sampling strategy of hospitalized COVID-19 patients in Hackensack Meridian Health network. *Convenience sampling was performed when assigning patients to our data team, and sampling bias is possible. 3325 of the 3438 (97%) available records were abstracted. **Follow-up until final study cut-off date of May 5, 2020. *** 53 patients who received toci did not have sufficient data (date of administration) to analyze Tocilizumab (toci); Hydroxychloroquine (HCQ).

Fig 2. Unadjusted association of treatment with hydroxychloroquine on overall survival among hospitalized COVID-19 patients.

Unadjusted Kaplan-Meier estimates of survival by treatment allocation to hydroxychloroquine (HCQ), azithromycin (AZI), both, or neither. Patients at risk at admission, day 10, day 20, and day 30 are shown. Patients still alive and in the hospital were censored as of May 5, 2020. Patients who had been discharged from the hospital were censored as of day 36 following hospital admission. 30-day mortality rates are shown for each treatment.

Fig 3. Unadjusted association of treatment with tocilizumab on overall survival among hospitalized ICU COVID-19 patients.

Unadjusted Kaplan-Meier estimates of survival by treatment allocation to tocilizumab (toci) or no toci. Patients at risk at admission, day 10, day 20, and day 30 are shown. Patients still alive and in the hospital were censored as of May 5, 2020. Patients who had been discharged from the hospital were censored as of day 36 following hospital admission. 30-day unadjusted mortality with and without tocilizumab is 46% versus 56%.