Intravenous Immunoglobulin Therapy in Pediatric Narcolepsy: A Nonrandomized, Open-Label, Controlled, Longitudinal Observational Study
1AP-HP, Pediatric Sleep Center, Hospital Robert-Debré, Paris, France; 2National Reference Centre for Orphan Diseases, Narcolepsy, Idiopathic Hypersomnia and Kleine-Levin Syndrome (CNR Narcolepsie-Hypersomnie), Paris, France; 3Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; 4Pharmacy Department, Hospital Robert-Debré, Paris, France; 5Pharmacy Faculty, Paris Descartes, Paris, France; 6Pediatric Nephrology Department, Hospital Robert-Debré, Paris, France; 7Paris Diderot University, Sorbonne Paris Cité, Paris, France
Previous case reports of intravenous immunoglobulins (IVIg) in pediatric narcolepsy have shown contradictory results.
This was a nonrandomized, open-label, controlled, longitudinal observational study of IVIg use in pediatric narcolepsy with retrospective data collection from medical files obtained from a single pediatric national reference center for the treatment of narcolepsy in France. Of 56 consecutively referred patients with narcolepsy, 24 received IVIg (3 infusions administered at 1-mo intervals) in addition to standard care (psychostimulants and/or anticataplectic agents), and 32 continued on standard care alone (controls).
For two patients in each group, medical files were unavailable. Of the 22 IVIg patients, all had cerebrospinal fluid (CSF) hypocretin ≤ 110 pg/mL and were HLA-DQB1*06:02 positive. Of the 30 control patients, 29 were HLA-DQB1*06:02 positive and of those with available CSF measurements, all 12 had hypocretin ≤ 110 pg/mL. Compared with control patients, IVIg patients had shorter disease duration, shorter latency to sleep onset, and more had received H1N1 vaccination. Mean (standard deviation) follow-up length was 2.4 (1.1) y in the IVIg group and 3.9 (1.7) y in controls. In multivariate-adjusted linear mixed-effects analyses of change from baseline in Ullanlinna Narcolepsy Scale (UNS) scores, high baseline UNS, but not IVIg treatment, was associated with a reduction in narcolepsy symptoms. On time-to-event analysis, among patients with high baseline UNS scores, control patients achieved a UNS score < 14 (indicating remission) less rapidly than IVIg patients (adjusted hazard ratio 0.18; 95% confidence interval: 95% confidence interval: 0.03, 0.95; p = 0.043). Shorter or longer disease duration did not influence treatment response in any analysis.
Overall, narcolepsy symptoms were not significantly reduced by IVIg. However, in patients with high baseline symptoms, a subset of IVIg-treated patients achieved remission more rapidly than control patients.
A commentary on this article appears in this issue on page 363.
Lecendreux M, Berthier J, Corny J, Bourdon O, Dossier C, Delclaux C. Intravenous immunoglobulin therapy in pediatric narcolepsy: a nonrandomized, open-label, controlled, longitudinal observational study. J Clin Sleep Med. 2017;13(3):441–453.
Please login to continue reading the full article
Subscribers to JCSM get full access to current and past issues of the JCSM.
Login to JCSM
Not a subscriber?
Join the American Academy of Sleep Medicine and receive a subscription to JCSM with your membership