Toculizimab and Steroid combination therapy in management of COVID 19 induced cytokine release syndrome
Background: Steroids are used to treat cytokine release syndrome(CRS) and inflammatory lung damage in severe COVID-19.Immunomodulatory drugs such as Toculizimab(TCZ) could be of incremental benefit.The aim of this retrospective cohort study was to evaluate the efficacy and safety of combination therapy of TCZ and steroid in management of COVID-19 associated CRS.
Methods: This retrospective cohort study was conducted at Noble hospital and Research Centre (NHRC),Pune,India between 2nd April and 2nd November 2020.Patients having rapidly worsening respiratory status, defined as presence of hypoxia(room air oxygen saturation< 90%) and tachypnea(respiratory rate >30 per minute) at rest or after minimal exertion despite use of antivirals and intravenous steroids(Methylprednisolone or Dexamethasone) were prescribed TCZ. It was given intravenously at a dose of 8 mg/kg bodyweight.The primary outcome was incidence of all-cause mortality during hospital admission.Secondary outcomes included need for mechanical ventilation and incidence of infectious complications.Baseline and time dependent risk factors significantly associated with death were identified by Relative risk estimation.
Results: Of 2831 admitted patients,515 (24.3% females) were administered TCZ and steroids. There were 135 deaths(26.2%),while 380 patients(73.8%) had clinical recovery.Mechanical ventilation was required in 242(47%) patients,of which 44.2%(107/242) recovered and were weaned off the ventilator. 37% patients could be managed in wards without need for intensive care while 53% patients needed only supplemental oxygen prior to recovery.Infectious complications like hospital acquired pneumonia,blood stream bacterial and fungal infections were seen in 2.13%, 2.13% and 0.06% patients respectively.Age ≥60 yrs(p=0.014), IL-6 ≥100 pg/ml(p = 0.002), D-dimer ≥1000 ng/ml(p< 0.0001),CT severity index ≥18(p< 0.0001) and systemic complications like lung fibrosis(p=0.019),cardiac arrhythmia(p< 0.0001),hypotension(p <0.0001) and encephalopathy(p <0.0001) were associated with increased risk of death on Relative risk estimation.
Conclusions: This study illustrates the robust efficacy of TCZ and steroids as an anti-inflammatory combination therapy in tackling CRS and needs timely administration to interrupt the cascade leading to irreversible lung damage and death.
