Higher Rates of Serious Adverse Events in Children With Rheumatic Diseases Receiving Tocilizumab

two doctors with little boy in hospital
two doctors with little boy in hospital
Researchers assessed the incidence rate and type of serious adverse events in children with inflammatory rheumatic diseases receiving tocilizumab.

Younger pediatric patients with juvenile idiopathic arthritis (JIA) and other inflammatory rheumatic diseases receiving tocilizumab (TCZ) have higher rates of serious adverse events (SAEs), according to study results published in Seminars in Arthritis and Rheumatism.

Tocilizumab has been approved for the treatment of JIA and other inflammatory rheumatic diseases, though data on the drug’s long-term safety are lacking. In a retrospective study of patient data identified from the Centre de reference des Maladies Rares (CEMARA) database, investigators aimed to determine the incidence rate and type of SAEs as a result of TCZ treatment in a pediatric setting.

A total of 104 children (64 girls) were included in the study, a majority of whom had systemic or polyarticular-course JIA. Indications for TCZ were categorized as lack of effectiveness of prior therapy, intolerance or adverse event, and other reasons. Clinical variables assessed during TCZ treatment included dose and interval, route of administration, and concomitant treatments and disease activity. Researchers defined SAEs as fatal or life-threatening events, events requiring inpatient hospitalization, or those leading to permanent or significant disability.

In 102 patients (98%), the TCZ indication was persistent disease activity. At the time of treatment initiation with TCZ, 85 patients (82%) were concomitantly treated with prednisone (n=68) and/or a nonbiologic disease-modifying antirheumatic drug (n=38). Over the course of the treatment period, total TCZ exposure was 215 patient-years (PY), with a median of 26 doses (interquartile range [IQR], 9-51 doses) per patient and a median treatment duration of 1.6 years (IQR, 0.5-2.7 years). Median patient age at initiation of treatment with TCZ was 8.9 years (IQR, 4.7-12.1 years).

Over the study period, 33 SAEs were observed in 26 patients (25%). The most common SAEs were serious infections (n=15; 7.0/100 PY), followed by severe infusion reactions (n=8) and macrophage activation syndrome (n=3). The overall incidence rate of SAEs was 15.3/100 PY. Patients with vs without SAEs were found to be significantly younger at both disease onset (2.0 vs 3.9 years; P= .034) and TCZ initiation (5.8 vs 9.7 years; P =.016), respectively.

After adjusting for diagnosis, the investigators found that age at disease onset remained an independent risk factor for SAEs (P =.025). In addition, all the patients who had severe infusion reactions (n=8; 3.7/100 PY) had an autoinflammatory disorder diagnosis and active disease at the time of the SAE occurrence.

The study was limited by its retrospective design, as the researchers were unable to determine causality of SAE with TCZ, and by small sample size.

Researchers concluded, “…ongoing careful monitoring of patients treated with TCZ, particularly young children and those with important systemic inflammation is required.”


Aeschlimann FA, Dumaine C, Wörner A, et al. Serious adverse events in children with juvenile idiopathic arthritis and other rheumatic diseases on tocilizumab – a real-world experience. Semin Arthritis Rheu. 2020;50(4):744-748.