Randomized, Controlled Trial of Intravenous Immunoglobulin for Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.
Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are hypothesized to occur as a result of cross-reactive antibodies produced in response to group A streptococcal infections. Previous research suggests that immunomodulatory therapies, such as intravenous immunoglobulin (IVIG), may lead to rapid and sustained symptom improvement in patients with PANDAS.



A total of 35 children meeting criteria for PANDAS and moderate to severe obsessive-compulsive disorder (OCD) were enrolled in a randomized-entry, double-blind, placebo-controlled, 6-week trial of IVIG (1 g/kg/day on 2 consecutive days), followed by optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions-Improvement (CGI-I) rating. "Responders" were defined, a priori, by a ≥ 30% decrease in CY-BOCS total score, and a "much" or "very much" improved rating on CGI-I.



During the double-blind phase, the mean decrease in CY-BOCS score was 24% ± 31% in the IVIG group (n = 17) and 12% ± 27% in the placebo group (n = 18), with six responders in the IVIG group (35%) versus four (22%) in the placebo group; these differences were not statistically significant. Twenty-four participants met criteria for nonresponse to double-blind infusion and received open-label IVIG at week 6. Among all participants, the mean CY-BOCS improvement from baseline was 55% ± 33% at week 12 and 62% ± 33% at week 24.



IVIG was safe and well tolerated. Between-group differences were smaller than anticipated, and the double-blind comparison failed to demonstrate superiority of IVIG over placebo. The observed open-label improvements indicate that future trials would benefit from larger sample sizes designed in part to aid in the identification of biomarkers predictive of a positive response to immunotherapy. Future investigations focused on the natural history of PANDAS are also warranted. Clinical trial registration information-Intravenous Immunoglobulin for PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections); http://clinicaltrials.gov/; NCT01281969ZIAMH002666.
Child Study Center at Yale University School of Medicine, New Haven, CT; Pediatric Neuropsychiatry and Immunology Program at Massachusetts General Hospital, Boston, MA.
Kyle A
KA
Williams
Pediatrics and Developmental Neuroscience Program of the National Institute of Mental Health, Bethesda, MD. Electronic address: swedos@mail.nih.gov.
Susan E
SE
Swedo
Pediatrics and Developmental Neuroscience Program of the National Institute of Mental Health, Bethesda, MD.
Cristan A
CA
Farmer
Child Study Center at Yale University School of Medicine, New Haven, CT.
Heidi
H
Grantz
Pediatrics and Developmental Neuroscience Program of the National Institute of Mental Health, Bethesda, MD.
Paul J
PJ
Grant
Pediatrics and Developmental Neuroscience Program of the National Institute of Mental Health, Bethesda, MD.
Precilla
P
D'Souza
Pediatrics and Developmental Neuroscience Program of the National Institute of Mental Health, Bethesda, MD.
Rebecca
R
Hommer
Child Study Center at Yale University School of Medicine, New Haven, CT.
Liliya
L
Katsovich
Child Study Center at Yale University School of Medicine, New Haven, CT.
Robert A
RA
King
Child Study Center at Yale University School of Medicine, New Haven, CT.
James F
JF
Leckman
D001327:Autoimmune Diseases / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D008297:Male; D009771:Obsessive-Compulsive Disorder / Q000628:therapy; D013290:Streptococcal Infections / Q000188:drug therapy*; D013297:Streptococcus pyogenes / Q000302:isolation & purification; D016896:Treatment Outcome
D016756:Immunoglobulins, Intravenous
IVIG; PANDAS; group A streptococcus pyogenes; obsessive-compulsive disorder