Background
Interleukin-6 (IL-6)-mediated hyperinflammation may contribute to the high mortality of
coronavirus disease 2019 (Covid-19).
Tocilizumab, an
IL-6 receptor blocking
monoclonal antibody, has been repurposed for
Covid-19, but prospective trials and dose-finding studies in
Covid-19 are lacking. Methods We conducted a phase 2 trial of low-dose
tocilizumab in hospitalized adult patients with
Covid-19, radiographic pulmonary infiltrate,
fever, and
C-reactive protein (CRP) >= 40 mg/L who did not require
mechanical ventilation. Dose cohorts were determined by a trial Operations Committee, stratified by CRP and epidemiologic risk factors. A range of doses from 40 to 200 mg (low-dose
tocilizumab) was evaluated, with allowance for one repeat dose at 24-48 hours. The primary objective was to assess the relationship of dose to
fever resolution and CRP response. Outcomes were compared with retrospective controls with
Covid-19. Correlative studies evaluating host antibody response were performed in parallel. Findings A total of 32 patients received low-dose
tocilizumab. This cohort had improved
fever resolution (75.0% vs. 34.2%, p = 0.001) and CRP decline (86.2% vs. 14.3%, p < 0.001) in the 24-48 hours following drug administration, as compared to the retrospective controls (N=41). The probabilities of
fever resolution or CRP decline did not appear to be dose-related in this small study (p=0.80 and p=0.10, respectively). Within the 28-day follow-up, 5 (15.6%) patients died. For patients who recovered, median time to clinical recovery was 3 days (IQR, 2-5). Clinically presumed and/or cultured bacterial
superinfections were reported in 5 (15.6%) patients. Correlative biological studies demonstrated that
tocilizumab-treated patients produced anti-SARS-CoV-2
antibodies comparable to controls. Interpretation Low-dose
tocilizumab was associated with rapid improvement in clinical and laboratory measures of hyperinflammation in hospitalized patients with
Covid-19. Results of this trial and its correlative biological studies provide rationale for a randomized, controlled trial of low-dose
tocilizumab in
Covid-19.