Neurological Adverse Effects Associated With Anti-tumor Necrosis Factor Alpha Antibodies in Pediatric Inflammatory Bowel Diseases

Objectives: Neurological adverse effects (NAEs) induced by biotherapies have been reported in the literature mainly in adult patients with inflammatory bowel disease (IBD), rheumatic diseases, or psoriasis. There are scant data in children. Aims of this study are to report and describe noninfective NAE associated with anti-TNF alpha antibodies in pediatric IBD, and to evaluate their incidence. Methods: We retrospectively collected all reports of NAE in pediatric IBD treated with anti-TNF alpha antibodies recorded in the French Pharmacovigilance Database. To estimate the national incidence of NAEs, we extrapolated data from the French regional inception population-based cohort EPIMAD. Results: Between 2000 and 2018, 231 adverse events in pediatric IBD exposed to anti-TNF alpha antibodies were reported to this Database. Seventeen NAEs (7.36%) were collected: 8 severe NAE (1 demyelinating neuropathy, 1 optic neuritis, 1 acute transverse myelitis, 1 polyradiculoneuritis, 1 sensorineural hearing loss, 1 seizure, 1 stroke, and 1 glioma), 7 moderate NAE (headaches), and 2 neuropsychic events. The median delay between anti-TNF alpha start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10 of 17 patients, anti-TNF alpha antibodies were stopped. Nine of 17 patients had a complete resolution (including 2 severe NAE) and 8 of 17 a partial resolution (including 6 severe NAE). We estimate the incidence of severe NAE in pediatric IBD treated with anti-TNF alpha antibodies at 1 case for 10,000 patients-year in France. Conclusions: NAE associated with anti-TNF alpha antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinue anti-TNF alpha therapy and to consider alternative treatment.