Real-world tocilizumab use in pediatric inpatients

ABSTRACT

INTRODUCTION: Tocilizumab (TCZ) is a recombinant monoclonal anti-interleukin-6 receptor antibody approved for use in children with juvenile idiopathic arthritis (JIA) and cytokine release syndrome (CRS) secondary to chimeric antigen receptor T-cell (CART) therapy. It is increasingly used off-label for other pediatric indications, though limited data exist describing safety and outcomes in these populations. This study describes TCZ use in JIA/CRS and other indications. Safety when administered during active infection and overall clinical outcomes were explored. METHODS: We performed a retrospective study of inpatients in a large children's hospital who received IV TCZ from 1/2016-5/2021 for any indication. Data included demographics, indication, dose amount, number of doses, safety events on days 0-7 after TCZ, use of extracorporeal support (ES), presence of concurrent infection, and survival to discharge. Exploratory analyses assessed characteristics associated with mortality. RESULTS: Data from 103 TCZ courses (n=87 pts) were analyzed. Median age was 14 yrs, and 66% had a primary oncologic diagnosis or had received myelosuppressive treatment (ONC/M). Indications for TCZ included CRS (56%), autoimmune disease (27%), GVHD (5%), and COVID-19 (4%). Median TCZ dose was 8 mg/kg. 18% of courses were administered during active infection, and ES was used in 15% of courses. New onset of ALT and AST >3x upper limit of normal occurred in 25% and 33% of courses, respectively. In patients without an ONC/M diagnosis (n=21), 10% of courses resulted in new onset neutropenia and 3% thrombocytopenia. Overall survival to discharge was 83%. Covariates associated with mortality by univariable analysis included an ONC/M diagnosis (OR 5.1 [95% CI 1.2-21], receipt of TCZ in an ICU (7 [1.8-41]), receipt of TCZ during active infection (3.8 [1-14), and use of ES (19 [4.6-91]). Only ES remained significant in multivariable analysis (OR 13 [3.1- 57]). CONCLUSIONS: TCZ is used for a range of pediatric inpatient indications, most commonly CRS. Risk factors for mortality are confounded by severity of illness, though administration during active infection was not independently associated with increased mortality. Prospective studies are needed to better understand the safety and efficacy of the off-label use of TCZ in children with inflammation.