Bertrand V¹, Massy N², Pigneur B³, Coopman S⁴, Durrieu G⁵, Gaboriau L⁶, Langlois V^7,8, Gower-Rousseau C⁹, Hugot JP¹⁰, Ruemmele FM^3,11,12; GETAID (Groupe d’Etude thérapeutique des Affections Inflammatoires du Tube Digestif) pédiatrique. J Pediatr Gastroenterol Nutr. 2020 Feb 7. doi: 10.1097/MPG.0000000000002654. [Epub ahead of print]

Author information

1 Département de pédiatrie, Hôpital Jacques Monod, BP 24, 76083 Le Havre cedex, FranceA list of investigators and study centres appears in the Appendix.

2 Centre Régional de Pharmacovigilance, Institut de Biologie Clinique, Hôpital Charles Nicolle, CHU de Rouen, 76031 ROUEN CEDEX.

3 Assistance Publique-Hôpitaux de Paris (APHP), Hôpital Necker Enfants Malades, Service de Gastroenterologie pédiatrique, Paris, France.

4 Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Jeanne de Flandre Lille University Children's Hospital, F-59000, France.

5 Centre Régional de Pharmacovigilance, Pharmacologie clinique, Faculté de médecine de Purpan, 37, allées Jules Guesde - 31073 Toulouse cedex.

6 Centre Régional de Pharmacovigilance, Pharmacologie médicale, Faculté de médecine, CHU Lille, 59037 Lille, France.

7 Département de médecine interne et maladies infectieuses, Hôpital Jacques Monod, BP 24, 76083 Le Havre cedex, France.

8 Département de neurophysiologie, centre de compétence neuro-musculaire régional, Hôpital Charles Nicolle, CHU de Rouen, 76031 ROUEN CEDEX.

9 Public Health Unit, Epimad Registry, Inserm UMR 995 LIRIC, Université Lille Nord de France, CHRU Lille, Lille, France.

10 Hôpital Robert Debré, Assistance Publique Hopitaux de Paris.

11 Université Sorbonne Paris Cité, Paris Descartes, Faculté de Médecine, Paris, France.

12 Institut IMAGINE, INSERM 1163, Paris, France.

Abstract

OBJECTIVES: Neurologic adverse effects (NAE) 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 non-infective NAE associated with anti-TNFα antibodies in pediatric IBD, and to evaluate their incidence.

METHODS: We retrospectively collected all reports of NAE in pediatric IBD treated with anti-TNFα 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-TNFα antibodies were reported to this Database. 17 NAE (7.36%) were collected: 8 severe NAE (one demyelinating neuropathy, one optic neuritis, one acute transverse myelitis, one polyradiculoneuritis, one sensorineural hearing loss, one seizure, one stroke, and one glioma), 7 moderate NAE (headaches), and 2 neuropsychic events. The median delay between anti-TNFα start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10/17 patients, anti-TNFα antibodies were stopped. 9/17 patients had a complete resolution (including 2 severe NAE) and 8/17 a partial resolution (including 6 severe NAE). We estimate the incidence of severe NAE in pediatric IBD treated with anti-TNFα antibodies at 1 case for 10 000 patients-year in France.

CONCLUSIONS: NAE associated with anti-TNFα antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinuate anti-TNFα therapy and to consider alternative treatment.