Serious adverse events in children with juvenile idiopathic arthritis and other rheumatic diseases on tocilizumab – a real-world experience

ABSTRACT Objectives To assess the incidence rate and type of serious adverse events (SAE) in children with rheumatic inflammatory diseases treated with the interleukin 6 blocker tocilizumab (TCZ). Methods A retrospective review of all consecutive patients diagnosed with an inflammatory rheumatic disease and receiving at least one dose of TCZ was performed in two French tertiary pediatric rheumatology centers between 01/2007 and 06/2019. SAE were defined as a life-threatening event and/or an event requiring hospital admission, leading to permanent disability or treatment discontinuation. Results One hundred four children (64 female) were included. Most children suffered from systemic (n=43) or polyarticular-course juvenile idiopathic arthritis (n=43). Median age at TCZ start was 8.9 years (IQR 4.7 – 12.1), most children had received prednisone (81%), and/or a biologic agent (84%) prior to TCZ. Median TCZ treatment duration was 1.6 years (IQR 0.5 – 2.7), total TCZ exposure 215 patient years. Thirty-three SAE were observed in 26 (25%) children (SAE 15.3/100 patient years), mostly infections and infusion reactions. Children with SAE were significantly younger at disease onset (p=0.034) and TCZ initiation (p=0.016). Children experiencing infusion reactions were more likely to have systemic JIA or another autoinflammatory disease (p=0.021), they all had active disease. At last follow up, 61 (59%) children remained on TCZ. Conclusion In this cohort, SAE and most commonly serious infections were observed in a quarter of children. Severe infusion reactions were associated with persistently active autoinflammatory disease. Ongoing careful monitoring of TCZ-treated patients, especially young children with marked systemic inflammation is required.