Adverse events of biological agents in pediatric rheumatologic diseases

ABSTRACT

Objectives

To evaluate adverse events (AEs) in pediatric patients with rheumatologic diseases being treated with approved or off-label biologic agents (BAs).

Methods

This observational, retrospective, multicenter study was conducted from 2010 to 2022 in patients under 18 years of age with rheumatic diseases who were receiving interleukin-1 antibodies (Anti-IL1), interleukin-6 antibodies (Anti-IL6), and tumor necrosis factor alpha inhibitors (anti-TNF). Efficacy, AEs, and timing of AEs were collected from electronic medical records.

Results

Three hundred and fifteen BAs were prescribed to 237 patients. Fifty AEs occurred in 44 patients (18.6%). Anti-TNF exposure was present in 8 (72.2%) of 11 patients with latent tuberculosis (TB) and in all 7 patients with herpes infections. Four of 6 patients (66.7%) with recurrent upper respiratory tract infections and 7 of 8 patients (87.5%) with local skin reactions were on Anti-IL1. The cutoff value for latent TB development was determined as 23.5 months by ROC analysis (AUC: 0.684 ± 0.072, p = 0.038, 95% CI: 0.54–0.82). In patients who used BA for 23.5 months or more, the risk of latent TB was 5.94-fold (p = 0.024, 95% CI: 1.26–27.97). Drug rash with eosinophilia and systemic symptoms (DRESS) occurred in 2 patients on anakinra, and anaphylaxis occurred in 1 patient on anti-IL6. There were no cases of malignancy or death in any patient.

Conclusion

The physician should be vigilant for latent TB in patients exposed to BA for more than 2 years. While local skin reactions are more prevalent in patients receiving anti-IL1, severe skin reactions such as DRESS may also occur.

KEYWORDS:

• Adverse events
• biological agents
• pediatric rheumatologic disease
• optic neuritis
• tuberculosis

Abbreviations

AAP: American Academy of Pediatrics; ACR: American College of Rheumatology; AE: Adverse Events; Anti-IL1: Interleukin-1 antibodies; Anti-IL6: Interleukin-6 antibodies; Anti-TNF: Tumour necrosis factor; BA: Biological agent; DMARD: Disease modifying anti-rheumatic drug; DRESS: Drug rash with eosinophilia and systemic symptoms; MKD: Mevalonate kinase deficiency; TB: Tuberculosis

Declaration of financial/other relationships

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. A reviewer on this manuscript has received an honorarium from IPGM for their review work. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Author contributions

Conceptualization: Merve Cansu Polat, Saniye Mertek. Methodology: Zeynep Birsin Özçakar, Elif Çelikel, Fatma Aydın, Zahide Ekici Tekin. Formal analysis and investigation: Atilla Halil Elhan. Writing – original draft preparation: Merve Cansu Polat. Writing – review and editing: Merve Cansu Polat, Banu Çelikel Acar, Nilgün Çakar Supervision: Banu Çelikel Acar, Nilgün Çakar.

Data availability statement

The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Additional information

Funding

This paper was not funded.