Département de Pédiatrie, Hôpital Jacques Monod, Le Havre Cedex.
Centre Régional de Pharmacovigilance, Institut de Biologie Clinique, Hôpital Charles Nicolle, CHU de Rouen, Rouen Cedex.
J Pediatr Gastroenterol Nutr. 2020 Jun;70(6):841-848. doi: 10.1097/MPG.0000000000002654.
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-TNFα antibodies in pediatric IBD, and to evaluate their incidence.
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.
Between 2000 and 2018, 231 adverse events in pediatric IBD exposed to anti-TNFα 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-TNFα start and NAE occurrence was 6 months (range: 13 days to 26 months). In 10 of 17 patients, anti-TNFα 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-TNFα antibodies at 1 case for 10,000 patients-year in France.
NAE associated with anti-TNFα antibodies in pediatric IBD are rare. In severe NAE, we recommend to discontinue anti-TNFα therapy and to consider alternative treatment.
生物疗法引起的神经不良反应（NAE）在文献中主要见于患有炎症性肠病（IBD）、风湿性疾病或银屑病的成年患者。儿童的数据很少。本研究的目的是报告和描述与儿童 IBD 中抗 TNFα 抗体相关的非感染性 NAE，并评估其发生率。
我们回顾性地收集了在法国药物警戒数据库中记录的所有与抗 TNFα 抗体治疗的儿科 IBD 相关的 NAE 报告。为了估计 NAE 的全国发生率，我们从法国区域性初始人群队列 EPIMAD 中推断数据。
在 2000 年至 2018 年间，该数据库共报告了 231 例儿科 IBD 暴露于抗 TNFα 抗体的不良事件。共收集到 17 例 NAE（7.36%）：8 例严重 NAE（1 例脱髓鞘神经病、1 例视神经炎、1 例急性横贯性脊髓炎、1 例多发性神经根炎、1 例感觉神经性听力损失、1 例癫痫发作、1 例中风和 1 例脑胶质瘤），7 例中度 NAE（头痛）和 2 例神经精神事件。抗 TNFα 开始与 NAE 发生之间的中位时间为 6 个月（范围：13 天至 26 个月）。在 17 例患者中，有 10 例停止使用抗 TNFα 抗体。17 例患者中有 9 例完全缓解（包括 2 例严重 NAE），17 例中有 8 例部分缓解（包括 6 例严重 NAE）。我们估计法国用抗 TNFα 抗体治疗的儿科 IBD 中严重 NAE 的发生率为每 10000 例患者年 1 例。
儿科 IBD 中与抗 TNFα 抗体相关的 NAE 罕见。在严重的 NAE 中，我们建议停止抗 TNFα 治疗，并考虑替代治疗。
