39.2 RANDOMIZED, CONTROLLED TRIAL OF INTRAVENOUS IMMUNOGLOBULIN FOR PEDIATRIC AUTOIMMUNE N EUROPSYCHIATRIC DISORDERS ASSOCIATED WITH STREPTOCOCCAL INFECTIONS

• Published in: Journal of the American Academy of Child and Adolescent Psychiatry Vol. 55; no. 10; p. S60
• Main Author: Williams, Kyle A
• Format: Journal Article
• Language: English
• Published: Baltimore Elsevier BV 01.10.2016
• Subjects: Antibodies; Anxiety Disorders; Biological markers; Biomarkers; Child & adolescent psychiatry; Children; Clinical assessment; Clinical trials; Dominance; Immunoglobulin; Immunoglobulins; Immunomodulation; Impressions; Inflammation; Intravenous administration; Obsessive compulsive disorder; Outcome Measures; Patients; Plasma; Statistical analysis; Streptococcus; Streptococcus infections; Variability; Video conferencing; Videoconferencing
• ISSN: 0890-8567; 1527-5418

Objectives: PANDAS is 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) or therapeutic plasma exchange may lead to rapid and sustained symptom improvement in PANDAS patients. To date, only one published, placebo-controlled trial has been conducted that investigate these therapies in PANDAS patients. Methods: Children (n = 35) meeting criteria for PANDAS and moderateto-severe OCD were enrolled in a randomized entry, double-blind, placebo-controlled 6-week trial of IVIG (1 g/kg per day on 2 consecutive days), followed by 6 weeks of optional open-label treatment for nonresponders, with follow-up at 12 and 24 weeks. Subjects were screened and evaluated by two study sites, the Yale Child Study Center and US NIH NIMH. Subjects were evaluated by the Yale site via a videoconferencing link and evaluated and treated in person at the NIMH. Primary outcome measures were the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions Improvement (CGI-I) ratings. Responders were defined a priori by a >30 percent decrease in CY-BOCS total score and responses of "much" or "very much" to show improvement on CGI-I. Results: The mean decrease during the double-blind phase in CY-BOCS score was 24 ± 31 percent in the IVIG group (n = 17) and 12 ± 27 percent in the placebo group (n = 18); however, this difference was not statistically significant. There were six responders in the IVIG group (35 percent) versus four (22 percent) in the placebo group during the blinded phase (not significant). Among all subjects, the mean CY-BOCS improvement from baseline was 55 ± 33 percent at week 12 and 62 ± 33 percent at conclusion. Conclusions: Between-group differences were smaller than anticipated, with a high degree of variability in response between subjects, and the doubleblind comparison failed to demonstrate superiority of IVIG over placebo. Future investigations in PANDAS may benefit from assessing biomarkers of systemic or neuronal inflammation before study participation or immunomodulatory treatment to decrease variability in response to immunemodulating treatments.